Advantageous therapies for disorders mediated by Ikaros or Aiolos

Abstract

New treatments for Ikaros and / or Aiolos mediated disorders are provided that comprise administering an effective amount of a cereblon binder that degrades Ikaros or Aiolos by the ubiquitin proteasome pathway.

Description

ADVANTAGEOUS THERAPIES FOR DISORDERS MEDIATED BY IKAROS OR AIOLOS CROSS-REFERENCE TO RELATED APPLICATIONS This application claims the benefit of U.S. Provisional Application No. 63 / 063,011 which was filed on August 7, 2020; U.S. Provisional Application No. 63 / 173,160 which was filed on April 9, 2021; and U.S. Provisional Application No. 63 / 212,463 which was filed on June 18, 2021. The entirety of these applications is hereby incorporated by reference for all purposes. FIELD OF THE INVENTION The invention provides therapeutic compositions, combinations, and uses thereof to treat disorders mediated by transcriptional proteins Ikaros (IKZF1) and / or Aiolos (IKZF3) via degradation of these proteins through the ubiquitin proteasome pathway. BACKGROUND The Ikaros family is a series of zinc-finger protein transcription factors that are important for certain physiological processes, particularly hematopoietic cells, and lymphocyte development (see Fan, Y. and Lu, D. “The Ikaros family of zinc-finger proteins” Acta Pharmaceutica Sinica B, 2016, 6:513-521). Ikaros (IKZF 1) was first discovered in 1992 (see Georgopoulos, K. et al. “Ikaros, an early lymphoid-specific transcription factor and a putative mediator for T cell commitment” Science, 1992, 258:802-812), and over the subsequent two decades four additional homologs have been identified: Helios (IKZF2), Aiolos (IKZF3), Eos (IKZF4), and Pegasus (IKZF5) (see John, L. B,, and Ward, A.C. “The Ikaros gene family: transcriptional regulators of hematopoiesis and immunity” Mol Immunol, 2011, 48:1272-1278). The distribution of various members of the Ikaros protein family within the body varies significantly. Ikaros, Helios, and Aiolos are primarily found in lymphoid cells and their corresponding progenitors, with Ikaros additionally detected in the brain, and Ikaros and Helios detected in erythroid cells. Eos and Pegasus are more wide spread, and found in skeletal muscle, the liver, the brain, and the heart (see Perdomo, J. et al. “Eos and Pegasus, two members of the Ikaros family of proteins with distinct DNA binding activities: J Biol Chem, 2000, 275:38347-38354; Schmitt, C. et al. “Aiolos and Ikaros: regulators of lymphocyte development, homeostasis and lymphoproliferation” Apoptosis, 2002, 7:277-284; Yoshida, T. and Georgopoulos, K. “Ikaros fingers on lymphocyte differentiation” Int J Hematol, 2014, 100:220-229). Ikaros is important for proper lymphocyte development. Deletion of the exons encoding the first three N-terminal zinc fingers leads to mice lacking T-cells, B-cells, natural killer (NK) cells, and their progenitors. Genetic alterations in Ikaros are correlated with a poor outcome in the treatment of acute lymphoblastic leukemia (ALL). Ikaros and Aiolos are involved in the proliferation of multiple myeloma cells and lymphoma cells. Multiple myeloma (MM) is a plasma cell malignancy typically characterized by the abnormal production of monoclonal immunoglobulin, bone marrow involvement, renal dysfunction, immune dysfunction, and skeletal damage. In the United States, MM represents nearly 1.8% of all new cancers. Although outcomes for subjects with MM have improved substantially over the past several decades, the disease remains incurable with a predicted five- year relative survival rate currently of 53.9%. As available therapies are not curative, almost all patients ultimately progress. Management of MM historically included chemotherapy, including alkylating agents together with corticosteroids. Treatment was further advanced in the 1980s with autologous stem cell transplants. In the 1990's the discovery of thalidomide (first-in-class immunomodulatory imide drug, IMiD®) efficacy in myeloma led to large shifts in treatment regimens and improvements in patient outcomes. The follow-on approved IMiD®s, lenalidomide and pomalidomide, are now widely used to treat MM, as is the first-in-class agent thalidomide. This class of agents binds the E3 ligase substrate-recognition adapter protein cereblon (CRBN) and promote the degradation of Ikaros (IKZF1) and Aiolos (IKZF3), resulting in antitumor effects, effects on the tumor microenvironment and immune modulation resulting in T-cell priming and antitumor activity. Many patients with MM are treated with multiple regimens containing one of these IMiDs. These drugs are now considered standard of care for the treatment of MM in numerous lines of therapy, in combination with agents including dexamethasone, anti-cluster of differentiation 38 (CD38) antibodies, and proteasome inhibitors, such as bortezomib. Although these agents have been successful in prolonging the progression free survival of patients with MM, patients generally relapse with shorter periods of progression free survival after each relapse. Recent studies with novel agents, belantamab and selinexor displayed improved outcomes in multiclass refractory myeloma resulting in recent FDA accelerated approvals; however, response rates were low (26- 31%) and progression free survival intervals short (3.7-4.9 months), thus underscoring the continued unmet medical need among these patients. Non-Hodgkin’s Lymphoma (NHL) is a heterogenous group of lymphoid malignancies originating from T, B or NK cells. It includes diffuse large B-cell lymphoma, anaplastic large-cell lymphoma, Burkitt lymphoma, lymphoblastic lymphoma, mantle cell lymphoma, peripheral T-cell lymphoma, follicular lymphoma, cutaneous T-cell lymphoma, lymphoplasmacytic lymphoma, marginal zone B-cell lymphoma, MALT lymphoma, and small-cell lymphocytic lymphoma. B-cell NHL predominates, while T-cell lymphomas are less common. Among new diagnosed patients with aggressive NHL, chemotherapy-based regimens including cyclophosphamide, vincristine, prednisone and daunorubicin (referred to as CHOP) remain the mainstay of therapy. In B-cell aggressive lymphomas, rituximab in combination with CHOP is the main therapy administered to new diagnosed patients. In some patients, particularly those with T-cell NHL, initial chemotherapy is followed by autologous stem cell rescue. In relapsed refractory populations, various targeted agents have been developed, thus improving treatment options in multiple subtypes of NHL, however these treatment options tend not to be curative. Additionally, the NHL subtypes are biologically heterogeneous limiting the development of therapeutic agents broadly across indications. In new diagnosed patients with aggressive lymphoma, initial treatment is frequently intense and administered with curative intent. Other than the addition of rituximab to CHOP in B-cell NHL and brentuximab to CHOP in anaplastic large cell lymphoma (ALCL), no other novel targeted agent has demonstrated survival improvements and therefore no others have been approved in treatment of naive patients. Recent therapeutic advances in relapsed NHL include Bruton Tyrosine Kinase (BTK) inhibitors, particularly for mantle cell lymphoma (MCL) and more indolent forms of NHL, chimeric antigen receptors T-cell (CAR-T) therapies which have been approved for diffuse large B-cell lymphoma (DBLCL) and MCL, and novel antibody drug conjugates like polatuzumab, belantamab, or tafasitamab which have been approved for DLBCL. Drugs recently approved for T-cell NHL include romidepsin, belinostat, and brentuximab. Relevant to the NHL population being studied in this protocol, lenalidomide has demonstrated clinical activity in both B-cell and T-cell NHL, including MCL, DLBCL and peripheral T-cell lymphoma (PTCL). Lenalidomide was studied in the relapsed / refractory (r / r) MCL population and was approved by the Food and Drug Administration (FDA) in June 2013 following results from the Phase Il EMERGE study which examined the efficacy and safety of lenalidomide in t / r subjects with MCL following bortezomib (overall response rate [ORR] 28%; median duration of response [DOR] 16.6 months). Lenalidomide is also active in DLBCL and PTCL. While lenalidomide and other novel targeted therapies have a modest to good response rate, durability of responses tends to be short across most NHL subtypes. Once patients relapse following 1-2 treatment regimens, the median duration of response tends to be low, and is dependent on patients having sufficient performance status and organ function to tolerate these therapies. Therefore, there remains an unmet medical need among patients with r / r NHL. Protein degradation is a highly regulated and essential process that maintains cellular homeostasis. The selective identification and removal of damaged, misfolded, or excess proteins is achieved via the ubiquitin-proteasome pathway (UPP). The UPP is central to the regulation of almost all cellular processes, including antigen processing, apoptosis, biogenesis of organelles, cell cycling, DNA transcription and repair, differentiation and development, immune response and inflammation, neural and muscular degeneration, morphogenesis of neural networks, modulation of cell surface receptors, ion channels and the secretory pathway, the response to stress and extracellular modulators, ribosome biogenesis and viral infection. Covalent attachment of multiple ubiquitin molecules by an E3 ubiquitin ligase to a terminal lysine residue marks the protein for proteasome degradation, where the protein is digested into small peptides and eventually into its constituent amino acids that serve as building blocks for new proteins. Defective proteasomal degradation has been linked to a variety of clinical disorders including Alzheimer’s disease, Parkinson’s disease, Huntington's disease, muscular dystrophies, cardiovascular disease, and cancer among others. Patent applications that describe certain protein degraders include WO 2020 / 210630, WO 2020 / 006262, WO 2020 / 010227, and WO 2020 / 010177. Patent applications filed by C4 Therapeutics, Inc., that describe compounds capable of binding to an E3 ubiquitin ligase and a target protein for degradation include: W0 / 2021 / 127561 titled “Isoindolinone And Indazole Compounds For The Degradation Of EGFR”; WO0 / 2021 / 086785 titled “Bifunctional Compounds”; W0 / 2021 / 083949 titled “Bifunctional Compounds for the Treatment of Cancer”; W0 / 2020 / 210630 titled “Tricyclic Degraders of Ikaros and Aiolos”; W0 / 2020 / 181232 titled “Heterocyclic Compounds for Medical Treatment”; ‘W0 / 2020 / 132561 titled “Targeted Protein Degradation”; W0 / 2019 / 236483 titled “Spirocyclic Compounds”; W02020 / 051235 titled “Compounds for the degradation of BRD9 or MTH1"; ‘W0 / 2019 / 191112 titled “Cereblon binders for the Degradation of Ikaros”; W0 / 2019 / 204354 titled “Spirocyclic Compounds”; W0 / 2019 / 099868 titled “Degraders and Degrons for Targeted Protein Degradation”; W0 / 2018 / 237026 titled “N / O-Linked Degrons and Degronimers for Protein Degradation”; WO 2017 / 197051 titled “Amine-Linked C3-Glutarimide Degronimers for Target Protein Degradation”; WO 2017 / 197055 titled “Heterocyclic Degronimers for Target Protein Degradation”; WO 2017 / 197036 titled “Spirocyclic Degronimers for Target Protein Degradation”; WO 2017 / 197046 titled “C3-Carbon Linked Glutarimide Degronimers for Target Protein Degradation”; and WO 2017 / 197056 titled “Bromodomain Targeting Degronimers for Target Protein Degradation.” It is an object of the present invention to provide new compositions of matter, combinations, formulations and uses thereof as well as processes of preparing compounds for the treatment of medical disorders mediated by Ikaros or Aiolos. SUMMARY OF THE INVENTION Compound 1 is a small molecule anti-cancer agent that binds with high affinity to the cereblon E3 ligase thereby creating a new surface on cereblon that interacts with IKZF1 and IKZF3 (see WO 2020 / 210630). As a result, IKZF1 and IKZF3 are efficiently ubiquitinated by the cereblon E3 ligase and degraded by the proteasome. The high cereblon binding affinity of Compound 1 enables rapid, deep, and durable degradation of IKZF1 / 3 resulting in potent activity in cancer cells, for example including but not limited to, hematopoietic cancers such as multiple myeloma and the multiple types of Non-Hodgkin’s Lymphoma. =o A ; | J uv 0” SAN (Compound 1) It has now been discovered that Compound 1, and other compounds described herein, can be administered to treat disorders mediated by Ikaros (IKZF1) and / or Aiolos (IKZF3) in a low dosage regimen once or twice a day, optionally with a drug holiday, in highly effective treatment regimens. For example, it has been discovered that anti-cancer treatment can be effective for a patient using one of the compounds described herein with a dosage of not more than about 500, 450, 400, 350, 325, 300, 275, 250, 225, 200, 175, 150, 125 or even 100, 75, 50, 45, 40, 35, 30, 25, 20,15, 10, 5, or 1 micrograms (ug) once a day (QD) or twice a day (BID). In certain embodiments, the patient is an adult (typically a human of at least 100 pounds or more, and sometimes even 125 or 150 pounds (e.g., 70 kg or more and at least typically 18 years old or more). In an alternative embodiment, the patient is pediatric (and may be less than 100, 125 or 150 pounds and typically less than 18 years old). Not only has it been discovered that Compound 1 is effective as a low dose therapy, but it can also be delivered with a drug holiday which is advantageous to the patient. For example, Compound 1 can be delivered once or twice a day for 21 days followed by a drug holiday of 7 days. Alternative dosing regimens are also useful, for example, including but not limited to those that increase or decrease the drug holiday by 1, 2, 3, 4, 5, 6, or 7 days. In certain embodiments Compound 1 or another compound described herein modulates the patient’s immune activity. For example, it has been discovered that Compound 1 activates proliferation of cytotoxic T-cells, which can be critical to anti-cancer therapy. Compound 1 or another compound described herein in a non-limiting embodiment can be administered daily or intermittently with dexamethasone. In certain embodiments, dexamethasone or another corticosteroid or another immunosuppressant or anti-inflammatory agent is administered every day without a drug holiday for the 28-day cycle. In other embodiments, the dexamethasone or another corticosteroid or another immunosuppressant or anti-inflammatory agent is administered with a drug holiday, which may be the same or different from that of Compound 1 or another compound described herein, In one aspect of the present invention the low dose Ikaros (IKZF1) and / or Aiolos (IKZF3) degrading compound is Compound 1 or a pharmaceutically acceptable salt thereof, Compound 1 has a high binding affinity to cereblon (dissociation constant Ka = 0.9 nM). Compound 1 promotes the degradation of >75% of steady state IKZF1 in multiple myeloma cells within 1.5 hours at 0.3 nM. The high binding affinity and degradation catalysis of Compound 1 enables potent cell growth inhibition in both previously untreated NCIH929 multiple myeloma cell lines (96% maximal growth inhibition, mean half maximal inhibitory concentration ICso of 0.071 nM) and NCIH929 cells made resistant to both lenalidomide and pomalidomide (70% maximal growth inhibition, mean ICso of 2.3 nM), The compounds described herein can be used to treat cancer cells that are resistant, refractive or unresponsive to standard of care therapies for cancers mediated by IKZF1 or IKZF3, including IMiDs including pomalidomide or any of those described in the Background or Detailed Description. As shown in Examples 12, Compound 1 has demonstrated strong anti-cancer activity in a panel of multiple myeloma cell lines (eight of twelve were responsive, mean ICso of 0.3 nM among responsive lines). Anti-cancer activity with Compound 1 was also demonstrated in several cell line models of various Non-Hodgkin's Lymphoma subtypes, including mantel cell lymphoma (MCL) (four of six lines tested were responsive mean ICso of 13 nM among the responsive lines), diffuse large B-cell lymphoma (DLBCL) (six of eleven germinal center B-cell like DLBCL and three of six activated B-cell DLBCL lines were responsive, with mean ICso of 12 nM and 1.6 nM respectively, amongst the responsive lines), anaplastic large cell lymphoma (ALCL) (four out of six cell lines were responsive, mean ICso of 1.7 nM among the responsive lines) and cutaneous T- cell lymphoma (CTCL) (three of four cell lines tested were responsive, mean ICso of 30 nM among the responsive lines). In mouse xenograft tumor models, Compound 1 demonstrated dose dependent efficacy from 3 pg’kg / day to 100 pgkg / day (see Example 13). In several tumor xenografts tested daily dosing of Compound 1 at dose of 30 pg / kg / day to 100 pg / kg / day led to durable tumor regression. As shown in Figure 45A, Figure 45B, Figure 45C, Figure 52, and others Compound 1 is more than 100-fold more potent than pomalidomide in a variety of cancer assays. In a mouse xenograft model Compound 1 has measurable plasma and tumor concentrations for longer than CC-92480 (currently in human clinical trials by Celgene, a subsidiary of Bristol Myers Squibb) despite being dosed at a 10-fold lower dose. It also takes significantly longer for IKZF3 levels to recover after treatment with Compound 1 than pomalidomide or CC-92480. For example, in an NCI-H929 tumor model it takes more than 48 hours for the IKZF3 level to reach 50% of its pretreatment level after administration of Compound 1, whereas both CC-92480 (at a x10 higher dose) and pomalidomide (at a x30 higher dose) reach pretreatment levels of IKZF3 within 48 hours of treatment As a result of the remarkable efficacy of Compound 1 and other compounds described herein, new advantageous treatments of disorders mediated by Ikaros (IKZF1) and / or Aiolos (IKZF3) have been discovered. In non-limiting embodiments of the invention, the Ikaros (IKZF1) and / or Aiolos (IKZF3) degrading compounds described herein can be used, in non-limiting examples as follows: 1. The treatment of a disorder mediated by Ikaros (IKZF1) and / or Aiolos (IKZF3) wherein the compound is administered in a low dose. For example, a dosage is not more than about 500, 450, 400, 350, 325, 300, 275, 250, 225, 200, 175, 150, 125, 100, 95, 90, 85, 80, 75, 70, 65, 60, 55, 50, 45, 40, 35, 30, 25, 20, 15, 10, 5, or 1 micrograms (ug) once a day (QD) or twice a day (BID), optionally with a drug holiday. 2. The treatment of a disorder mediated by Ikaros (IKZF 1) and / or Aiolos (IKZF3) wherein a compound described herein is administered in an effective amount in a dosage regimen that includes a drug holiday, for example a holiday of 1, 2, 3, 4, 5,6, 7,8, 9, 10, 11, 12, 13, or 14 days in a 28-day treatment cycle. 3. The treatment of a disorder mediated by Ikaros (IKZF1) and / or Aiolos IKZF3) wherein a blood or tissue sample is first taken from the patient and the concentration of one or more biomarkers, for example a tumor immunity marker (e.g., a cytokine, tumor infiltrating lymphocyte, T-cell activation and / or proliferation, or a B-cell marker such as BCMA or M-protein, or a combination thereof); an apoptotic marker (e.g., total and / or cleaved caspase-1, caspase-3, caspase-7, PARP, BIM, or survivin, or a combination thereof); or a zinc finger protein (e.g., IKZF 1, IKZF3, ZFP91, WIZ, or SALL4, or a combination thereof), is determined, and wherein if the patient has a statistically different concentration of the biomarker including but not limited to about 5, 10, 15 or 20% different than a healthy person then Compound 1 or a pharmaceutically acceptable salt thereof or another compound described herein is administered to the patient, 4, The treatment of a disorder mediated by Ikaros (IKZF 1) and / or Aiolos (IKZF3) wherein a blood or tissue sample is first taken from the patient and the concentration of one or more biomarkers, for example IRF-1, caspase-3, IL-2, and / or IFN-y, is determined, and wherein if the patient has a statistically lower concentration of the biomarker than a healthy person, including but not limited to up to about 5, 10, 15 or 20% lower, then Compound 1 or a pharmaceutically acceptable salt thereof or another compound described herein is administered to the patient. 5. The treatment of a disorder mediated by Ikaros (IKZF1) and / or Aiolos (IKZF3) wherein a blood or tissue sample is first taken from the patient and the concentration of one or more biomarkers, for example cyclin D1, E2F1, ZFP91, SALL4, IRF-4, BLIMP1, and / or MYC is determined, and wherein if the patient has a statistically higher concentration of biomarker including but not limited to up to about 5, 10, 15 or 20% higher than a healthy person then Compound 1 or a pharmaceutically acceptable salt thereof or another compound described herein is administered to the patient. 6. The treatment of a disorder mediated by Ikaros (IKZF1) and / or Aiolos (IKZF3) wherein the patient is administered Compound 1 or a pharmaceutically acceptable salt thereof or another compound described herein and then a blood or tissue sample is taken from the patient and the concentration of one or more biomarkers, for example IRF-1, caspase-3, IL-2, and / or IFN-y, is determined, wherein if the concentration of the biomarker is not significantly increased, for example by at least about 1.25, 1.5, 1.75, or 2-fold, then the dose of the compound is increased. The treatment of a disorder mediated by Ikaros IKZF1) and / or Aiolos (IKZF3) wherein the patient is administered Compound 1 or a pharmaceutically acceptable salt thereof or another compound described herein and then a blood or tissue sample is taken from the patient and the concentration of one or more biomarkers, for example cyclin D1, E2F1, ZFP91, SALL4, IRF-4, BLIMP1, and / or MYC is determined, wherein if the concentration of the biomarker is not significantly decreased, for example by about 1.25, 1.5, 1.75, or 2-fold, then the dose of the compound is increased. 7. The treatment of a disorder mediated by Ikaros (IKZF1) and / or Aiolos (IKZF3) wherein the patient is administered Compound 1 or a pharmaceutically acceptable salt thereof or another compound described herein and then a blood or tissue sample is taken from the patient and the concentration of one or more biomarkers, for example a tumor immunity marker (e.g, a cytokine, tumor infiltrating lymphocyte, T-cell activation and / or proliferation, and B-cell markers such as BCMA or M-protein, or a combination thereof); an apoptotic marker (e.g., total and / or cleaved caspase-1, caspase-3, caspase-7, PARP, BIM, or survivin, or a combination thereof); or a zinc finger protein (e.g., IKZF1, IKZF3, ZFP91, WIZ, or SALL4, or a combination thereof), is determined, wherein if the concentration of the biomarker has not changed significantly, for example by at least about 1.25, 1.5, 1.75, or 2-fold, then the dose of the compound is increased. 8. The treatment of an activated diffuse large B-cell lymphoma, germinal diffuse large B-cell lymphoma, extranodal natural killer (NK) cell lymphoma, or extranodal T-cell lymphoma, with an effective amount of a compound described herein or a pharmaceutically acceptable salt thereof. 9. The treatment of a disorder mediated by Ikaros (IKZF1) and / or Aiolos (IKZF3) wherein the compound is administered in a low dose. For example, a dosage is not more than about 500, 450, 400, 350, 325, 300, 275, 250, 225, 200, 175, 150, 125 or even 100, 75, 50 or 25 micrograms (pg) once a day (QD) or twice a day (BID), optionally with a drug holiday. 10. The treatment of a disorder mediated by Ikaros (IKZF1) and / or Aiolos (IKZF3) wherein a compound described herein is used in combination with a BTK inhibitor, for example a BTK inhibitor selected from acalabrutinib, spebrutinib, zanubrutinib, LOXO0-305, evobrutinib, TG-1701, tolebrutinib, BIIB091, DZD-9008, HZ-A-018, orelabrutinib, ACO05S8TA, SN1011, rilzabrutinib, ARQ 531, DTRMWXHS-12, JNJ-64264681, branebrutinib, ibrutinib, and fenebrutinib, 11. The treatment of a disorder mediated by Ikaros (IKZF1) and / or Aiolos (IKZF3) wherein a compound described herein is used in combination with a CD38 antibody, for example a CD38 antibody selected from felzartamab, daratumumab, GBR 1342, TAK-573, CID-103, OKTI10, STI-6129, SGX301, TAK-079, and mezagitamab. 12. The treatment of a disorder mediated by Ikaros (IKZF1) and / or Aiolos (IKZF3) wherein a compound described herein is used in combination with a proteasome inhibitor, for example a proteasome inhibitor selected from bortezomib, carfilzomib, ixazomib citrate, oprozomib, delanzomib, lactacystin, epoxomicin, MG132, MG-262, CEP-18770, NEQOSH101, TQB3602, and KZR-616. 13. The treatment of a disorder mediated by Ikaros (IKZF1) and / or Aiolos (IKZF3) wherein a compound described herein is used in combination with an IMiD for example an IMiD selected from thalidomide, pomalidomide, lenalidomide, ibertomide, (CC-92480, CC- 90009, and CC-99282. 14. The treatment of a disorder mediated by Ikaros (IKZF1) and / or Aiolos (IKZF3) wherein a compound described herein is used in combination with an HDAC inhibitor, for example an HDAC inhibitor selected from trapoxin B, sodium phenylbutyrate, tacedinaline, mocetinostat, BRD73954, BG45, domatinostat, cay 10603, HPOB, TMP269, nexturastat A, Santacruzamate A, splitomicin, LMK-235, sodium butyrate, pivaloyloxymethyl butyrate, pyroxamide, abexinostat, resminostat, givinostat, quisinostat, Psammaplin A, KD5170, 1- Alaninechlamydocin, depudecin, panobinostat, ricolinostat, vorinostat, and CUDC-101. 15. The treatment of a disorder mediated by Ikaros (IKZF1) and / or Aiolos (IKZF3) wherein a compound described herein is used in combination with another compound, for example a compound selected from selinexor, oxaphenamide, belantamab mafodotin, denosumab, zoledronic acid, plerixafor, eltrombopag, ipilumumab, palbociclib, ricolinostat, afuresertib, dinaciclib, filanesib, indatuximab ravtansine, masitinib, sonidegib, sotatercept, ulocuplumab, and urelumab. 16. A treatment of cancer mediated by Ikaros (IKZF1) and / or Aiolos (IKZF3) comprising administering an effective amount of Compound 1 to activate proliferation of T-cells. These new treatments offer advantages over presently approved treatments of cancer. For example, a compound described herein can be administered at a lower dose than first generation IMiDs; can penetrate the blood brain barrier to treat a central nervous system (CNS) involved cancer, for example a CNS involved lymphoma; can treat a cancer that has relapsed or is refractory to a standard of care regimen, including a first generation IMiD treatment; and / or can provide a longer period of progression free survival to the patient than 1% generation IMiDs, for example thalidomide, pomalidomide, and lenalidomide. In certain embodiments a compound described herein is about 30, 40, 50, 60, 70, 80, 90, 100, 500, or even 1,000 times more potent in vivo than thalidomide, pomalidomide, lenalidomide, or CC-92480. In certain embodiments a compound described herein causes durable degradation of IKZF1 and / or IKZF3 (e.g. IKZF1 and / or IKZF3 levels take 12 hours, 18 hours, 24 hours, 36 hours, 48 hours, or longer to return to pretreatment levels). This durable degradation is a result of high in vivo efficacy, metabolic stability, and / or selectivity. In one aspect, the compound used in the treatments described herein is selected from: =o Nn } bv 0’ SAY (Compound 1) CO 2 0 Oo =0 A NH J (Compound 2) Oo w C0 AIT 4 o i =0 4 J—NH Oo (Compound 3) o] oral =0 NH a NS NC” C _ 0 = OX “F (Compound 4) =0 A NH J NL ! yw Oo SA (Compound 5) Oo 0 Yd Fp =o i NH 0 (Compound 6) o A N— » Na. pu; 0 =o A J—NH Oo (Compound 7) 0 ww CO H- J J 0 =0 od A NH 0 (Compound 8) 0 on =0 L J—NH Oo (Compound 9) Oo Kin "9 0 =0 i J—NH oO (Compound 10) AY Oo w CO NYA J & po 9 (Compound 11) con =0 (Compound 12) 0 I J 5 = d NH F LJ N= =O He J—NH Oo SN MEd - (Compound 13) or a pharmaceutically acceptable salt thereof, Oo : . C- HANH ) J N— tically acceptable salt thereof. A compound described herein modulates immune system activity, for example activating IFN-alpha, IFN-beta, or IFN-gamma. By activating the immune system, the compound can more effectively treat cancer. This immunomodulatory activity increases the efficacy of a compound described herein with another anti-cancer agent such as daratumumab. In certain embodiments the degradation of IKZF1 and IKZF3 from malignant B or T cells result in tumor cell death, and their depletion from the tumor microenvironment results in T-cell activation. The compound may for example be provided for oral, parenteral or topical delivery. In certain embodiments, the compound is provided in a solid, gel or liquid dosage form for oral delivery, or may be provided intravenously. In some embodiments, the selected compound is provided as a softshell capsule or a solid dosage form tablet for oral administration. In certain embodiments, the dose strengths of the pharmaceutical composition is about 1 pg, 5 ug, 10 pg, 15 pug, 20 pg, 25 pg, 50 ug, 75 ug, 100 pg, 125 pg, 150 pg, 175 pg, 200 pg, 225 pg, 250 ug, 275 ng, 300 ug, 325 ug, 350 ug, 375 ug, 400 ug, 425 pg, 450 pg, 475 pg, 500 pg, 525 pg, 550 pg, 575 ug, 600 ug, 625 ug, 650 ug, 675 ug, 700 ug, 725 ug, 750 pg, 775 ug, or 800 ug, which may in one nonlimiting aspect be given once daily (QD) or twice a day (BID) on days 1-21 of a 28- day treatment cycle. The compound may for example be provided for oral or parenteral delivery. In certain embodiments, the compound is provided in a solid, gel or liquid dosage form for oral delivery, or may be provided intravenously. In some embodiments, the selected compound is provided as a softshell capsule or tablet for oral administration. In certain embodiments, the dose strengths of the solid or gel dosage form is 25 pg, 50 ug, 100 pg, 200 ug, 300 ug or 400 pg, which may in one nonlimiting aspect be given once daily (QD) on days 1-210of a 28-day cycle. In a principal aspect the compound used in the treatments described herein is Compound 1 or a pharmaceutically acceptable salt thereof, In certain embodiments, any of the compounds described herein have at least one desired isotopic substitution of an atom, at an amount about the natural abundance of the isotope, i.e., enriched. In certain embodiments, the compound includes a deuterium or multiple deuterium atoms. Other features and advantages of the present invention will be apparent from the following detailed description and claims, Brief Description of the Figures FIG. 1A is a dose-response curve describing the effect of Compound 1 on H929 cell viability compared to pomalidomide as described in Example 9. The x-axis is the concentration of Compound 1 or pomalidomide in nM and the y-axis is the % H929 cell viability after 96 hours. FIG. 1B is a dose-response curve describing the effect of Compound 1 on IKZF1 degradation compared to pomalidomide as described in Example 9. The x-axis is the concentration of Compound 1 or pomalidomide in nM and the y-axis is the % IKZF1 remaining after 1.5 hours. FIG. 2A is a scatter plot of data from tumor lysates analyzed by multiplexed quantitative proteomics in mice treated with Compound 1 for 4 hours. Tumor lysates were analyzed by multiplexed quantitative proteomics and fold changes in relative abundance comparing treatment with Compound 1 to that with DMSO control were depicted in a scatter plot. Log2 fold changes are shown in the x axis and negative Logl0 adjusted P values are shown on the y axis. The horizontal dashed line marks the statistical significance (P adjusted < 0.01) and the vertical line marks fold change > 2. IKZF1 and IKZF3 are the only significantly downregulated proteins with a fold change of 5.5 and 4.1, respectively. Data shown are of biological duplicates measured in a single 10-plex TMT experiment with a total of 7,903 proteins quantified. P values were derived from a moderated t-statistic and corrected for multiple hypothesis testing using a Benjamini— Hochberg approach. The experimental procedure is provided in Example 10. FIG. 2B is a scatter plot of data from tumor lysates analyzed by multiplexed quantitative proteomics in mice treated with Compound 1 for 24 hours. Tumor lysates were analyzed by multiplexed quantitative proteomics and fold changes in relative abundance comparing treatment with Compound 1 to that with DMSO control were depicted in a scatter plot. Log2 fold changes are shown in the x axis and negative Logl0 adjusted P values are shown on the y axis. The horizontal dashed line marks the statistical significance (P adjusted < 0.01) and the vertical line marks fold change > 2. The experimental procedure is provided in Example 10. FIG. 3 is a dose-response curve describing the effect of Compound 1 with and without bortezomib (proteasome inhibitor) or MLN-4924 (neddylation inhibitor) on Ikaros degradation. As described in Example 11, Ki-JK cells were exposed to Compound 1 with and without bortezomib or MLN-4924 and the IKZF1 concentration was determined by flow cytometry at 1.5, 3, and 6 hours for Compound 1 and 6 hours for the combination of Compound 1 and bortezomib or MLN-4924. The x-axis is the concentration of Compound 1 alone or in combination with bortezomib or MLLN-4924. The y-axis is the remaining concentration of IKZF1-488 measured as a percent relative to DMSO. FIG. 4 is a graph of the effect of Compound 1 in mice bearing multiple myeloma NCI- H929 cells as described in Example 13. Compound 1 was administered orally (PO) every day (QD) at four different concentrations (3 pg / kg, 10 pg / kg, 30 pg / kg, and 100 pg / kg) and compared to pomalidomide. The x-axis is the time measured in days and the y-axis is NCI-H929 tumor volume measured in mm?3. FIG. 5 is a graph of the effect of Compound 1 in mice bearing multiple myeloma RPMI- 8226 cells as described in Example 13. Compound 1 was administered orally (PO) every day (QD) at four different concentrations (3 pg / kg, 10 pg / kg, 30 pg / kg, and 100 pg / kg) and compared to pomalidomide. The x-axis is the time measured in days and the y-axis is RPMI-8226 tumor volume measured in mm?. FIG. 6 are images comparing mice administered Compound 1 and vehicle. Mice were imaged using IVIS Lumina II as described in Example 14. FIG. 7 is a graph of the bioluminescence signal of mice administered Compound 1 orally (PO) every day (QD) or vehicle and imaged using IVIS Lumina II as described in Example 14. The x-axis is time measured in days and the y-axis is the MM1S-Luc systemic BLI (total bioluminescence signal) measured in photons / 10°. FIG. 8 is a graph of the tumor volume of mice injected with NCI-H929 pomalidomide resistant cells and administered Compound 1 (100 pg / kg) or pomalidomide (3000 pg / kg) orally (PO) every day (QD) as described in Example 15. The x-axis is the time measured in days and the y-axis is the tumor volume measured in mm?, FIG. 9 is a graph of the tumor volume of mice injected with refractory multiple myeloma cell line RPMI-8226. As described in Example 15, mice were injected with RPMI-8226 tumors and the tumors were allowed to grow to a volume of 109-158 mm? (28 days after implantation). Vehicle treated animals continued treatment until tumors reached a MTV (mean tumor volume) of 2211 mm®. Pomalidomide treated animals were crossed over onto Compound 1 (100 pg / kg / day) at day 17 for 21 additional days. The x-axis is the time measured in days and the y-axis is the tumor volume measured in mm?. FIG. 10s a graph of the tumor volume of mice injected with lymphoma REC1 mantle cells and administered Compound 1 or pomalidomide as described in Example 16. Compound 1 was administered at four different concentrations (3 pg / kg, 10 pg / kg, 30 pg / kg, or 100 pg / kg) and pomalidomide was administered at a dose of 3000 pg / kg. Both agents were administered orally (PO) every day (QD). The x-axis is the time measured in days and the y-axis is the tumor volume measured in mm?>. FIG. 11 is a graph of the tumor volume of mice injected with lymphoma TMD8 DLBCL and administered Compound 1 (100 pg / kg) or pomalidomide (3000 pg / kg) orally (PO) every day (QD) as described in Example 16. The x-axis is the time measured in days and the y-axis is the tumor volume measured in mm?3. FIG. 12 is a graph of the tumor volume of mice injected with KI-JK ALCL tumors and administered Compound 1 at either 30 pg / kg or 100 pg / kg PO QD (orally every day) or pomalidomide (3000 pg / kg, QD PO) or CC-92480 (1000 pg / kg, QD PO) as described in Example 17. The mice were dosed for 21 days. The x-axis is the time measured in days and the y-axis is the tumor volume measured in mm? FIG. 13A is a bar graph of IKZF1 protein expression in mice injection with KI-JK ALCL tumors and administered Compound 1 or pomalidomide as described in Example 17. Mice were sacrificed and tumors harvested at 6 and 24 hours post single dose. The x-axis is labeled with the time post dose that the animal was sacrificed and the y-axis is the percent of IKZF1 protein compared to the vehicle control normalized to GAPDH. FIG. 13B is a bar graph of IRF4 protein expression in mice injection with KI-JK ALCL tumors and administered Compound 1 or pomalidomide as described in Example 17. Mice were sacrificed and tumors harvested at 6 and 24 hours post single dose. The x-axis is labeled with the time post dose that the animal was sacrificed and the y-axis is the percent of IRF4 protein compared to the vehicle control normalized to GAPDH. FIG. 14 is a graph of the tumor volume of mice injected with DL-40 ALCL tumors and administered Compound 1, pomalidomide, or CC-92480 as described in Example 18. Compound 1 was administered at three different concentrations (10 pg / kg, 30 pg / kg, or 100 pg / kg) orally (PO) every day (QD). Pomalidomide was administered at a dose of 3000 pg / kg orally every day. CC- 92480 was administered at a dose of 300 pg / kg orally every day. The x-axis is the time measured in days and the y-axis is the tumor volume measured in mm?. FIG. 15A is a graph of IKZF1 protein expression in mice injected with DL-40 ALCL tumors and administered Compound 1 or pomalidomide as described in Example 18. Mice were sacrificed and tumors harvested at 1, 4, and 24 hours post single dose. The x-axis is labeled with the time post dose that the animal was sacrificed and the y-axis is the percent of IKZF1 protein compared to the vehicle control normalized to GAPDH. FIG. 15B is a western blot measuring the concentration of IKZF1 and IKZF3 in mice injected with DL-40 ALCL tumors and administered Compound 1 or pomalidomide as described in Example 18. The concentration was determined when mice were sacrificed at 1, 4, and 24 hours post single dose. DL-40 ALCL tumors FIG. 16 is a graph of the tumor volume of mice injected with DL-40 ALCL tumors and administered Compound 1 or pomalidomide as described in Example 19. Compound 1 was administered at five different concentrations (3 pg / kg, 10 pg / kg, 30 pg / kg, 100 pg / kg, or 300 ug / kg) orally (PO) every day (QD). Pomalidomide was administered at a dose of 3000 pg / kg orally every day. The x-axis is the time measured in days and the y-axis is the tumor volume measured inmm3 FIG. 17 is a graph of the tumor volume of mice injected with DL-40 ALCL tumors and administered Compound 1 as described in Example 19. Compound 1 was administered at three different concentrations (30 pg / kg, 100 pg / kg, or 300 pg / kg) orally (PO) every day (QD). The x- axis is the time measured in days and the y-axis is the body weight change measured in percent. FIG. 18 is a graph of the tumor volume of mice injected with KI-JK ALCL tumors and administered Compound 1 (100 pg / kg orally (PO) every day (QD)) as described in Example 20. The x-axis is the time measured in days and the y-axis is the tumor volume measured in mm? FIG. 19 is a graph of IKZF1, IKZF3, IRF-4, caspase-3, and IRF-1 protein expression in mice injected with KI-JK ALCL tumors and administered Compound 1 as described in Example 20. The x-axis is labeled with the time post dose that the animal was sacrificed and the y-axis is the percent of protein compared to the vehicle control normalized to GAPDH. FIG. 20 is a graph comparing the effect of Compound 1, ibrutinib, and the combination of Compound 1 and ibrutinib on TMD8 tumor volume in mice as described in Example 13. Compound 1 was administered at a dose of 50 pg / kg orally every day and ibrutinib was administered at a dose of 12.5 mg / kg orally every day. The combination was dosed at each agent’s respective dose. The x-axis is the time measured in days and the y-axis is the tumor volume measured in mm?3. FIG. 21 is a graph of the percent survival of mice bearing TMD8 DLBCL administered Compound 1, ibrutinib, and the combination of Compound 1 and ibrutinib as described in Example 21. Compound 1 was administered at a dose of 50 pg / kg orally every day and ibrutinib was administered at a dose of 12.5 mg / kg orally every day. The combination was dosed at each agent’s respective dose. The x-axis is days post-dose and the y-axis is the percent survival. FIG. 22 is a graph comparing the effect of Compound 1, dexamethasone, and the combination of Compound 1 and dexamethasone on RPMI-8226 multiple myeloma tumor volume in mice as described in Example 22. Dexamethasone was administered at a dose of 5 mg / kg intravenously (IV) every week (QW) and Compound 1 was administered at a dose of 10 pg / kg orally every day. Compound 1 was dosed in combination with dexamethasone at each agent’s respective dose levels and schedules. The x-axis is the time measured in days and the y-axis is the tumor volume measured in mm?3. FIG. 23 is a graph of the percent survival of mice bearing RPMI-8226 multiple myeloma tumors administered Compound 1, dexamethasone, and the combination of Compound 1 and dexamethasone as described in Example 22. Dexamethasone was administered at a dose of 5 mg / kg intravenously (IV) every week (QW) and Compound 1 was administered at a dose of 10 ng / kg orally every day. Compound 1 was dosed in combination with dexamethasone at each agent’s respective dose levels and schedules. The x-axis is days post-dose and the y-axis is the percent survival. FIG. 24 is a graph measuring the concentration of IKZF1 and IKZF3 in a monkey administered Compound 1. As described in Example 23, one monkey was administered Compound 1 and blood was collected at 0, 4, and 24 hours post-dose to determine the concentration of IKZF1 and IKZF3. The x-axis is the time post-dosing measured in hours and the y-axis is the mean fluorescent intensity of IKZF1 and IKZF3. FIG. 25A is a graph measuring the plasma concentration of Compound 1 or Compound 14 following the administration of Compound 1 (60 pg / kg or 100 pg / kg) PO to monkeys as described in Example 24. The x-axis is time measured in hours and the y-axis is plasma concentration measured in ng / mL. FIG. 25B is a graph measuring the plasma concentration of Compound 1 or Compound 14 following the administration of Compound 1 (30 mg / kg) PO to a rat as described in Example 24. The x-axis is time measured in hours and the y-axis is plasma concentration measured in ng / mL. FIG. 26A is a graph measuring the effect of Compound 1 (100 pg / kg, QD PO) compared to vehicle on tumor volume in mice injected with H929 tumors as described in Example 25. The x-axis is treatment length measured in days and the y-axis is H929 tumor volume measured in 3 mm. FIG. 26B is a graph measuring the effect of Compound 2 (100 pg / kg, QD PO) compared to vehicle on tumor volume in mice injected with H929 tumors as described in Example 25. The x-axis is treatment length measured in days and the y-axis is H929 tumor volume measured in mm?3. FIG. 26C is a graph measuring the effect of Compound 3 (100 pg / kg, QD PO) compared to vehicle on tumor volume in mice injected with H929 tumors as described in Example 25. The x-axis is treatment length measured in days and the y-axis is H929 tumor volume measured in 3 mm?>. FIG. 26D is a graph measuring the effect of Compound 4 (100 pg / kg, QD PO) compared to vehicle on tumor volume in mice injected with H929 tumors as described in Example 25. The x-axis is treatment length measured in days and the y-axis is H929 tumor volume measured in 3 mm-. FIG. 26E is a graph measuring the effect of Compound 5 (100 pg / kg, QD PO) compared to vehicle on tumor volume in mice injected with H929 tumors as described in Example 25. The x-axis is treatment length measured in days and the y-axis is H929 tumor volume measured in 3 mm?>. FIG. 26F is a graph measuring the effect of Compound 6 (100 pg / kg, QD PO) compared to vehicle on tumor volume in mice injected with H929 tumors as described in Example 25. The x-axis is treatment length measured in days and the y-axis is H929 tumor volume measured in 3 mm-. FIG. 26G is a graph measuring the effect of Compound 7 (100 pg / kg, QD PO) compared to vehicle on tumor volume in mice injected with H929 tumors as described in Example 25. The x-axis is treatment length measured in days and the y-axis is H929 tumor volume measured in 3 mm? FIG. 26H is a graph measuring the effect of Compound 8 (100 pg / kg, QD PO) compared to vehicle on tumor volume in mice injected with H929 tumors as described in Example 25. The x-axis is treatment length measured in days and the y-axis is H929 tumor volume measured in mm?3. FIG. 261 is a graph measuring the effect of Compound 9 (100 pg / kg, QD PO) compared to vehicle on tumor volume in mice injected with H929 tumors as described in Example 25. The x- axis is treatment length measured in days and the y-axis is H929 tumor volume measured in mm?. FIG. 26] is a graph measuring the effect of Compound 10 (100 pg / kg, QD PO) compared to vehicle on tumor volume in mice injected with H929 tumors as described in Example 25. The x-axis is treatment length measured in days and the y-axis is H929 tumor volume measured in mm?3. FIG. 26K is a graph measuring the effect of Compound 11 (100 pg / kg, QD PO) compared to vehicle on tumor volume in mice injected with H929 tumors as described in Example 25. The x-axis is treatment length measured in days and the y-axis is H929 tumor volume measured in 3 mm?>. FIG. 26L is a graph measuring the effect of Compound 12 (100 pg / kg, QD PO) compared to vehicle on tumor volume in mice injected with DL-40 ALCL tumors as described in Example 25. The x-axis is treatment length measured in days and the y-axis is H929 tumor volume measured 3 3 mmm. FIG. 26M is a graph measuring the effect of Compound 13 (100 pg / kg, QD PO) compared to vehicle on tumor volume in mice injected with H929 tumors as described in Example 25. The x-axis is treatment length measured in days and the y-axis is H929 tumor volume measured in 3 mm?>. FIG. 27 is a graph demonstrating the in-vitro binding of Compound 1 to purified cereblon- DDBI1 was measured via fluorescent polarization experiment. Compound 1 (circles) or reference compound (Pomalidomide) competes with Alexa-647 based fluorescence probe for binding to cereblon-DDB1. Probe displacement results in a decreased level of fluorescent polarization that is used to calculate the fraction of the bound probe using the signals from positive and negative controls. Error bars represent the standard deviation (SD). Measured Kd values are as follows: Compound 1: Ka= 0.9 = 0.5 nM; Pomalidomide Ka = 712 = 140 nM. The fluorescent polarization experiment is described in Example 26. FIG. 28 is a dose-response curve describing the displacement of a cereblon binding tracer molecule by Compound 1 or pomalidomide in 293T cells expressing cereblon-NanoLuc fusion as described in Example 27. The x-axis is the concentration of Compound 1 or pomalidomide in nM and the y-axis is the % NanoBRET signal relative to cells treated with cereblon binding tracer only (100%) or without tracer (0%). 50% of the tracer was displaced by Compound 1 with ICso = 0.4 nM and by pomalidomide with ICso = 644 nM. FIG. 29 is a dose-response curve describing the effect of Compound 1 on IKZF1 degradation compared to pomalidomide as described in Example 9. The x-axis is the concentration of Compound 1 or pomalidomide in nM and the y-axis is the % IKZF1 remaining after treatment with Compound 1 or pomalidomide for 1 or 2 hours. FIG. 30 is a western blot showing Aiolos and Ikaros levels remaining in H929 cells after 4 hours treatment with Compound 1 or pomalidomide in dose response. The method for this experiment is described in Example 28. FIG. 31 is a dose-response curve describing the effect of Compound 1 on Caspase 3 / 7 activity in NCIH929 multiple myeloma cell line compared to pomalidomide after 72 hour treatment as described in Example 29. The x-axis is the concentration of Compound 1 or pomalidomide in nM and the y-axis is the luminescence signal (RLU) measured following addition of Caspase 3 / 7 substrate reagents. The method for this experiment is described in Example 29. FIG. 32 is a plot showing the effect of Compound 1 on growth of eight multiple myeloma cell lines compared to pomalidomide as described in Example 30. The x-axis is the concentration of Compound 1 or pomalidomide in nM that inhibited cellular growth at 96 hours by 50% (ICso) and the y-axis is the cell line tested. FIG. 33 is a graph showing the in vivo efficacy of Compound 1 and pomalidomide in the treatment of female NOD SCID mice bearing NCI-H929 multiple myeloma xenograft tumors. Mice we treated with the vehicle control, a dose response (3, 10, 30 and 100 pg / kg / day) of Compound 1, or 3000 pg / kg / day of pomalidomide for 21 days. All compounds were administered orally (PO) on a daily basis (QD) After 21 days of dosing tumors were monitored for regrowth. Arrow indicates rechallenging with 30 pg / kg / day of Compound 1 starting on Day 40. The x-axis is the time measured in days and the y-axis is NCI-H929 tumor volume measured in mm>. This assay is described in Example 31. FIG. 34 is a graph of the bioluminescence signal of mice administered Compound 1 orally (PO) every day (QD) or vehicle and imaged using IVIS Lumina II as described in Example 14. The x-axis is time measured in days and the y-axis is the MMI1S-Luc systemic BLI (total bioluminescence signal) measured in photons / 106. FIG. 35 is in vivo efficacy of Compound 1 and pomalidomide in the treatment of female CB17 SCID mice bearing RPM-8226 multiple myeloma xenograft tumors. Mice were treated with the vehicle control, a dose (3, 10, 30 and 100 pg / kg / day) of Compound 1, or 3000 pg / kg / day of pomalidomide for 21 days. All compounds were administered orally (PO) on a daily basis (QD). Tumors are graphed individually and represented as the percent of their original volume, as shown on the y-axis. FIG. 36 is a graph of IKZF3 protein expression in mice injected with RPMI-8226 tumors and administered a dose response of Compound 1 as described in Example 32. The x-axis is labeled with the time post dose that the animal was sacrificed and the y-axis is the percent of protein compared to the vehicle control normalized to GAPDH. FIG. 37 is a graph of IKZF1, IKZF3 and IRF-4, tumor protein expression in mice injected with RPMI-8226 MM tumors and administered Compound 1 as described in Example 32. The x- axis is labeled with the time post dose that the animal was sacrificed and the y-axis is the percent of protein compared to the vehicle control normalized to GAPDH. FIG. 38 is a western blot evaluating the levels of cereblon, IKZF1, and IKZF3 levels in H929 cells that were untreated (parental), treated with DMSO (LTC; long term culture), lenalidomide, or pomalidomide for four months. Vinculin was used as a loading control. The western blot was conducted using the method described in Example 33. FIG. 39 describes the effect of Compound 1 on growth of IMiD-resistant NCIH929 multiple myeloma cells compared to pomalidomide as described in Example 34. The x-axis is the concentration of Compound 1 or pomalidomide in nM and the y-axis is the % viability of IMiD- resistant NCIH929 cells after 96 hours relative to untreated cells. FIG. 40 is a graph of the tumor volume of mice injected with refractory multiple myeloma cell line RPMI-8226. Mice were dosed orally daily with the vehicle control, pomalidomide (3000 pg / kg / day) or Compound 1 (100 ug / kg / day) for 35 days, with the exception of the pomalidomide group. For this group pomalidomide dosing was stopped on Day 17 and replaced with Compound 1 dosing (100ug / kg / day) for the remainder of the study. This experiment is described in more detail in Example 15. FIG. 41 is a graph comparing the effect of Compound 1, dexamethasone, and the combination of Compound 1 and dexamethasone on RPMI-8226 multiple myeloma tumor volume in mice as described in Example 22. Dexamethasone was administered at a dose of 5 mg / kg intravenously (IV) every week (QW) and Compound 1 was administered at a dose of 10 pg / kg or 100 pg / kg orally every day. Compound 1 at 10 pg / kg was dosed in combination with Dexamethasone at each agent’s respective dose levels and schedules. The x-axis is the time measured in days and the y-axis is the tumor volume measured in mm? FIG. 42 is a graph comparing the effect of Compound 1, dexamethasone, and the combination of Compound 1 and dexamethasone on RPMI-8226 multiple myeloma tumor volume in mice as described in Example 22. Dexamethasone was administered at a dose of 5 mg / kg intravenously (IV) every week (QW) and Compound 1 was administered at a dose of 10 pg / kg orally every day. Compound 1 was dosed in combination with dexamethasone at each agent’s respective dose levels and schedules. Once a tumor volume reached 1000 mm? the animal was removed from the study and recorded as a death. The y-axis is the probability of an animal’s survival on a particular treatment and the x-axis is the numbers of days an animal has survived. FIG. 43 is a graph of IKZF1, IKZF3 and IRF-4, tumor protein expression in mice injected with REC1 MCL tumors and administered Compound 1 as described in Example 35. The x-axis is labeled with the time post dose that the animal was sacrificed, and the y-axis is the percent of protein compared to the vehicle control normalized to GAPDH. FIG. 44 is a graph of E2F1 and Cyclin D1, protein expression in mice injected with REC1 MCL tumors and administered Compound 1 as described in Example 35. The x-axis is labeled with the time post dose that the animal was sacrificed, and the y-axis is the percent of protein compared to the vehicle control normalized to GAPDH. FIG. 45A, FIG. 45B, and FIG. 45C are dot bar graphs describing the effect of Compound 1 on growth of NHL cell lines compared to pomalidomide as described in Example 37. The x-axis is the concentration of Compound 1 or pomalidomide in nM that inhibited cellular growth at 96 hr by 50% (ICso) and the y-axis is the cell line tested. Open symbols indicate that growth was not inhibited by more than 50% at the highest tested concentration (100 nM or 10 pM for Compound 1, 10 uM for pomalidomide, and 10 pM for CC-92480) and therefore ICso was not determined. FIG. 46 is a western blot taken from mice bearing established KI-JK xenografts that were administered a single dose of Compound 1 (100 pg / kg) or daily for 5 days. Tumors were collected at 4 and 24 hours post single dose and 24 hours post 5 daily doses. Tumors were analyzed by western blot for IKZF1 and IRF-4 levels. The experimental procedure is described in Example 38. FIG. 47 is a line graph showing the change in tumor volume in mice bearing Mino xenograft tumors that were treated with Compound 1 (100 pg / kg) once a day orally, rituximab once a week IV (10 mg / kg), or the combination of the two at their respective doses. Data are expressed as mean tumor volumes + SEM values. The experimental procedure is described in Example 39. FIG. 48 is a line graph showing change in concentration over time after treating mice bearing established NCI-H929 xenograft tumors were treated with a single dose of Compound 1 (100 pg / kg) or CC-92480 (1000 pg / kg). Plasma and tumor samples were collected at 1, 4, 24, and 48 hours post single dose and analyzed by LC-MS / MS. Data are expressed total compound concentration + SEM values. The experimental procedure is provided in Example 40. FIG. 49 is a line graph showing change in concentration over time after treating mice bearing established NCI-H929 xenograft tumors were treated with a single dose of Compound 1 (100 pg / kg), CC-92480 (1000 pg / kg), or pomalidomide (3000 pg / kg). Tumor samples were collected at 1, 4, 24, and 48 hours post single dose and analyzed by western blot for IKZF3 levels. Data are expressed as percent of IKZF3 remaining in comparison to the vehicle control and normalized to GAPDH + SEM values. The experimental procedure is provided in Example 40. FIG. 50 is a line graph showing change in tumor volume over time after treating mice bearing established NCI-H929 xenograft tumors were treated with Compound 1 (100 pg / kg), CC- 92480 (1000 pg / kg), or pomalidomide (3000 pg / kg) orally daily for 18 days. Tumor volume and body weights were measured twice a week. Data are expressed as mean tumor volumes + SEM values. The experimental procedure is provided in Example 40. FIG. 51 is a dose-response curve describing the effect of Compound 1 on Caspase 3 / 7 activity in TMDS8 cell line compared to pomalidomide after 48 hr treatment as described in Example 41. The x-axis is the concentration of Compound 1 or pomalidomide in nM and the y- axis is the luminescence signal (RLU) relative to DMSO-treated controls measured following addition of caspase 3 / 7 substrate reagents. FIG. 52 is a dose-response curve describing the effect of Compound 1 on TMDS cell viability compared to pomalidomide after 96-hour treatment as described in Example 42. The x- axis is the concentration of Compound 1 or pomalidomide in nM and the y-axis is the % cellular viability relative to DMSO-treated controls measured following addition of Cell Titer Glo reagents. FIG. 53 is a line graph demonstrating the effect of Compound 1, ibrutinib, and the combination of Compound 1 and ibrutinib on Mino mantle cell lymphoma xenograft tumors. Mice were administered Compound 1 at a dose of 30 pg / kg / day, ibrutinib at a dose of 25 mg / kg, the combination of ibrutinib and Compound 1 at their respective dose levels, or the vehicle control orally daily for 34 days. The x-axis is the time measured in days and the y-axis is the tumor volume measured in mm’, Statistics were done using a paired t test in GraphPad Prism software. The experimental procedure is provided in Example 44, FIG. 54 is a line graph demonstrating the effect of Compound 1, CC-92480, pomalidomide, or the vehicle control on RPMI-8226 multiple myeloma xenograft tumors. Mice were administered Compound 1 at a dose of 100 pg / kg / day, CC-92480 at 1000 pg / kg / day, or pomalidomide at 3000 ug / kg / day orally daily for 19 days. The x-axis is the time measured in days and the y-axis is the tumor volume measured in mm?, Statistics were done using a paired t test in GraphPad Prism software. The experimental procedure is provided in Example 45. FIG. 55 is a line graph demonstrating the effect of Compound 1, CC-92480, pomalidomide, or the vehicle control on IKZF3 levels in RPMI-8226 multiple myeloma xenograft tumors. Mice were administered Compound 1 at a dose of 100 pg / kg / day, CC-92480 at 1000 pg / kg / day, or pomalidomide at 3000 pg / kg / day orally daily for 7 days. Tumors were sampled at 4 and 24 hours post single dose, and 24 hours post 3, 5, and 7 daily doses. Data is represented as percent of target present in the vehicle control and normalized for total protein. Error bars represent + SEM values. The experimental procedure is provided in Example 45. FIG. 56 is a line graph demonstrating the effect of Compound 1, bortezomib, and the combination of Compound 1 and bortezomib in NCI-H929 xenografts. Mice bearing established NCI-H929 xenografts were administered doses of Compound 1 (10 pg / kg), bortezomib (0.5 mg / kg), the combination of Compound 1 and bortezomib, or the vehicle control for 14 days. Compound 1 was dosed orally daily while bortezomib was dosed on a every other week schedule intravenously. Statistical analysis was done on day 14, the last day all animals were on study, by two-way ANOVA using GraphPad Prism software. Data are expressed as mean tumor volumes + SEM. FIG. 57 is a line graph demonstrating the effect of Compound 1, bortezomib, and the combination of Compound 1 and bortezomib in NCI-H929 xenografts. Mice bearing established NCI-H929 xenografts were administered doses of Compound 1 (10 ng / kg), bortezomib (0.25 mg / kg), the combination of Compound 1 and bortezomib, or the vehicle control for 14 days. Compound 1 was dosed orally daily while bortezomib was dosed twice a week intravenously. Statistical analysis was done on day 14, the last day all animals were on study, by two-way ANOVA using GraphPad Prism software. Data are expressed as mean tumor volumes + SEM. FIG. 58 is a line graph containing the effect of Compound 1, Compound 2, Compound 15, CC-92480, or Pomalidomide on the concentration of IL2 secreted from anti-CD3 stimulated T- cells after a six-day incubation. The x-axis is the concentration of compound in nM and the y-axis is the fold-change relative to DMSO treated control wells. The experimental procedure is provided in Example 46. FIG. 59 is a line graph containing the effect of Compound 1, Compound 2, Compound 15, CC-92480, or Pomalidomide on the concentration of IFNg secreted from anti-CD3 stimulated T- cells after a six-day incubation. The x-axis is the concentration of compound in nM and the y-axis is the fold-change relative to DMSO treated control wells. The experimental procedure is provided in Example 46. FIG. 60 is a line graph containing the effect of Compound 1, Compound 2, Compound 15, CC-92480, or Pomalidomide on the concentration of IL21 secreted from anti-CD3 stimulated T- cells after a six-day incubation. The x-axis is the concentration of compound in nM and the y-axis is the fold-change relative to DMSO treated control wells. The experimental procedure is provided in Example 46. FIG. 61 is a line graph containing the effect of Compound 1, Compound 2, Compound 15, CC-92480, or Pomalidomide on the concentration of IL9 secreted from anti-CD3 stimulated T- cells after a six-day incubation. The x-axis is the concentration of compound in nM and the y-axis is the fold-change relative to DMSO treated control wells. The experimental procedure is provided in Example 46. FIG. 62 is a line graph containing the effect of Compound 1, Compound 2, Compound 15, CC-92480, or Pomalidomide on the concentration of IL4 secreted from anti-CD3 stimulated T- cells after a six-day incubation. The x-axis is the concentration of compound in nM and the y-axis is the fold-change relative to DMSO treated control wells. The experimental procedure is provided in Example 46. FIG. 63 is a line graph containing the effect of Compound 1, Compound 2, Compound 15, CC-92480, or Pomalidomide on the concentration of TNF-alpha secreted from anti-CD3 stimulated T-cells after a six-day incubation. The x-axis is the concentration of compound in nM and the y-axis is the fold-change relative to DMSO treated control wells. The experimental procedure is provided in Example 46. FIG. 64 is a line graph containing the effect of Compound 1, Compound 2, Compound 15, CC-92480, or Pomalidomide on the concentration of IL17A secreted from anti-CD3 stimulated T- cells after a six-day incubation. The x-axis is the concentration of compound in nM and the y-axis is the fold-change relative to DMSO treated control wells. The experimental procedure is provided in Example 46. DETAILED DESCRIPTION OF THE INVENTION The new treatments, for example low dosage regimens, described herein are based on the discovery that the described compounds are unusually highly active Ikaros and Aiolos degraders. It is thought that Compound 1 is the most potent IKZF1 / 3 degrader publicly disclosed to date. Data described herein and otherwise obtained establishes markedly improved antitumor effect of the combination of Compound 1 and dexamethasone. The Compounds described herein, and notably Compound 1, are significantly more efficacious than pomalidomide across NHL models, including PTCL and MCL, both in vitro and in vivo. Therefore, these compounds can be used in preference over thalidomide, lenalidomide, and pomalidomide, in NHL subtypes where classical IMiDs have demonstrated clinical activity but have not been widely adopted as standard of care (MCL, DLBCL, PTCL, etc.). It has been discovered that the compounds described herein can be administered to treat disorders mediated by Ikaros (IKZF1) and / or Aiolos (IKZF3) in a low dosage regimen once or twice a day, optionally with a drug holiday, in highly effective treatment modalities. For example, it has been discovered that treatment can be effective for a patient using one of the compounds described herein with a dosage of not more than about 500, 450, 400, 350, 325, 300, 275, 250, 225, 200, 175, 150, 125 or even 100, 75, 50 or 25 micrograms (pg) once a day (QD) or twice a day (BID). In certain embodiments, the patient is an adult (typically a human of at least 100 pounds or more, and sometimes even 125 or 150 pounds (e.g., 70 kg or more and at least typically 18 years old or more). In an alternative embodiment, the patient is pediatric (and may be less than 100, 125 or 150 pounds and typically less than 18 years old). In certain embodiments, the dosage includes a drug holiday. A drug holiday is a time period during which the patient is not administered the active compound. Treatment cycles, for the purposes of this disclosure are usually based on a 28 day cycle. For example, the patient may be administered the active compound or its pharmaceutically acceptable salt for 21 continuous days and not administered the chemotherapeutic for 7 days during the 28 day cycle, and then optionally the regimen is repeated once or several or more times. In certain examples, one of the compounds described herein may be administered once or twice a day for at least 13, 14 15, 16, 17, 18, 19, 20, 21, 22,23, 24, 25, 26 or 27 continuous days, and then a holiday taken until the next 28 day cycle. In some embodiments, the compound is administered once or twice a day for at least 20, 21, 22, 23 or 24 continuous days followed by a drug holiday until the end of the 28 day cycle. In yet another embodiment, the drug is administered every day without a holiday to achieve continuous dosing during the dosing regimen period, which may be 1, 2, 3, or 4 weeks, or even 1, 2, 3,4, 5 or 6 or more continual or periodic months. In another embodiment, the use of a compound described herein eliminates the need for an off-cycle period, drug holiday, or reduction in co-administered anti-neoplastic compound concentration during treatment. In yet another embodiment, the cycle period is greater than 28 days, such as greater than 30 or 35 days, and an appropriate on-cycle and off-cycle regimen determined by the patient’s healthcare specialist. In certain embodiments, the Ikaros (IKZF1) and / or Aiolos (IKZF3) degrader is administered in combination with one or more additional therapeutic agents. Non-limiting examples of therapeutic agents that can be used in combination with a degrader described herein include: 1. A BTK inhibitor selected from acalabrutinib, spebrutinib, zanubrutinib, LOX0Q-305, evobrutinib, TG-1701, tolebrutinib, BIIB091, DZD-9008, HZ-A-018, orelabrutinib, ACO05S8TA, SNI1011, rilzabrutinib, ARQ 531, DTRMWXHS-12, JINJ-64264681, branebrutinib, ibrutinib, and fenebrutinib. 2. A CD38 antibody selected from felzartamab, daratumumab, GBR 1342, TAK-573, CID- 103, OKT10, STI-6129, SGX301, TAK-079, and mezagitamab. 3. A proteasome inhibitor selected from ixazomib citrate, oprozomib, delanzomib, lactacystin, bortezomib, carfilzomib, VLX1570, epoxomicin, MGI132, MG-262, CEP-18770, NEQOSH101, TQB3602, and KZR-616. 4, An IMiD selected from pomalidomide, lenalidomide, thalidomide, iberdomide CC-92480, CC-90009, and CC-9928%2. 5. An HDAC inhibitor selected from trapoxin B, sodium phenylbutyrate, tacedinaline, mocetinostat, BRD73954, BG45, domatinostat, cay 10603, HPOB, TMP269, nexturastat A, Santacruzamate A, splitomicin, LMK-235, sodium butyrate, pivaloyloxymethyl butyrate, pyroxamide, abexinostat, resminostat, givinostat, quisinostat, Psammaplin A, KD5170, 1-Alaninechlamydocin, depudecin, and CUDC-101. 6. A compound selected from selinexor, oxaphenamide, belantamab mafodotin, denosumab, zoledronic acid, plerixafor, eltrombopag, ipilumumab, palbociclib, ricolinostat, afuresertib, dinaciclib, filanesib, indatuximab ravtansine, masitinib, sonidegib, sotatercept, ulocuplumab, and urelumab. L Definitions Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this application belongs. In the specification, singular forms also include the plural unless the context clearly dictates otherwise. Although methods and materials similar or equivalent to those described herein can be used in the practice and testing of the present application, suitable methods and materials are described below. All publications, patent applications, patents, and other references mentioned herein are incorporated by reference. The references cited herein are not admitted to be prior art to the claimed application. In the case of conflict, the present specification, including definitions, will control. In addition, the materials, methods, and examples are illustrative only and are not intended to be limiting. Compounds are described using standard nomenclature. Unless defined otherwise, all technical and scientific terms used herein have the same meaning as is commonly understood by one of skill in the art to which this invention belongs. In certain embodiments, of each compound described herein, the compound may be in the form of a racemate, enantiomer, mixture of enantiomers, diastereomer, mixture of diastereomers, tautomer, N-oxide, or isomer, such as a rotamer, as if each is specifically described unless specifically excluded by context. The terms “a” and “an” do not denote a limitation of quantity, but rather denote the presence of at least one of the referenced items. The term “or” means “and / or”. Recitation of ranges of values are merely intended to serve as a shorthand method of referring individually to each separate value falling within the range, unless otherwise indicated herein, and each separate value is incorporated into the specification as if it were individually recited herein. The endpoints of all ranges are included within the range and independently combinable. All methods and treatments described herein can be performed in a suitable order unless otherwise indicated herein or otherwise clearly contradicted by context. The use of examples, or exemplary language (e.g., “such as”), is intended merely to better illustrate the invention and does not pose a limitation on the scope of the invention unless otherwise claimed. The present invention includes compounds described herein with at least one desired isotopic substitution of an atom, at an amount above the natural abundance of the isotope, i.e., enriched. Isotopes are atoms having the same atomic number but different mass numbers, i.e., the same number of protons but a different number of neutrons. If isotopic substitutions are used, the common replacement is at least one deuterium for hydrogen. More generally, examples of isotopes that can be incorporated into compounds of the invention include isotopes of hydrogen, carbon, nitrogen, oxygen, and fluorine such as 2H, 3H, ''C, Be, lc, 15N, 170, #0, and °F, respectively. In one non-limiting embodiment, isotopically labelled compounds can be used in metabolic studies (with, for example “C), reaction kinetic studies (with, for example 2H or H), detection or imaging techniques, such as positron emission tomography (PET) or single-photon emission computed tomography (SPECT) including drug or substrate tissue distribution assays, or in radioactive treatment of patients. Additionally, any hydrogen atom present in the compound of the invention may be substituted with an '*F atom, a substitution that may be particularly desirable for PET or SPECT studies. Isotopically labeled compounds of this invention and prodrugs thereof can generally be prepared by carrying out the procedures disclosed in the schemes or in the examples and preparations described below by substituting a readily available isotopically labeled reagent for a non-isotopically labeled reagent. By way of general example and without limitation, isotopes of hydrogen, for example, deuterium (*H) and tritium (*H) may be used anywhere in described structures that achieves the desired result. Alternatively, or in addition, isotopes of carbon, e.g., °C and 1C, may be used. Isotopic substitutions, for example deuterium substitutions, can be partial or complete. Partial deuterium substitution means that at least one hydrogen is substituted with deuterium. In certain embodiments, the isotope is 90, 95 or 99% or more enriched in an isotope at any location of interest. In one non-limiting embodiment, deuterium is 90, 95 or 99% enriched at a desired location. In one non-limiting embodiment, the substitution of a hydrogen atom for a deuterium atom can be provided in any compound described herein. For example, when any of the groups are methyl or ethyl the alkyl residue may be deuterated (in non-limiting embodiments, CDHz, CD2H, CDs, CH2CDs, CD2CDs, CHDCH2D, CH2CDs, CHDCHD:, ete.). The compounds of the present invention may form a solvate with a solvent (including water). Therefore, in one non-limiting embodiment, the invention includes a solvated form of the compounds described herein. The term "solvate" refers to a molecular complex of a compound of the present invention (including a salt thereof) with one or more solvent molecules. Non-limiting examples of solvents are water, ethanol, isopropanol, dimethyl sulfoxide, acetone and other common organic solvents. The term "hydrate" refers to a molecular complex comprising a compound of the invention and water. Pharmaceutically acceptable solvates in accordance with the invention include those wherein the solvent may be isotopically substituted, e.g. D20, de- acetone, ds-DMSO. A solvate can be in a liquid or solid form. A “dosage form” means a unit of administration of an active agent. Examples of dosage forms include tablets, capsules, injections, suspensions, liquids, emulsions, implants, particles, spheres, creams, ointments, suppositories, inhalable forms, transdermal forms, buccal, sublingual, topical, gel, mucosal, and the like. A “dosage form” can also include an implant, for example an optical implant, As used herein “endogenous” refers to any material from or produced inside an organism, cell, tissue or system. As used herein, the term “exogenous” refers to any material introduced from or produced outside an organism, cell, tissue or system. By the term “modulating,” as used herein, is meant mediating a detectable increase or decrease in the level of a response in a patient compared with the level of a response in the patient in the absence of a treatment or compound, and / or compared with the level of a response in an otherwise identical but untreated patient. The term encompasses perturbing and / or affecting a native signal or response thereby mediating a beneficial therapeutic response in a patient, preferably, a human. “Parenteral” administration of a compound includes, e.g., subcutaneous (s.c.), intravenous (i.v.), intramuscular (i.m.), or intrasternal injection, or infusion techniques. As used herein, “pharmaceutical compositions” is a composition comprising at least one active agent such as a selected active compound described herein, and at least one other substance, such as a carrier. “Pharmaceutical combinations” are combinations of at least two active agents which may be combined in a single dosage form or provided together in separate dosage forms with instructions that the active agents are to be used together to treat any disorder described herein. As used herein, a “pharmaceutically acceptable salt” is a derivative of the disclosed compound in which the parent compound is modified by making inorganic and organic, acid or base addition salts thereof with a biologically acceptable lack of toxicity. The salts of the present compounds can be synthesized from a parent compound that contains a basic or acidic moiety by conventional chemical methods. Generally, such salts can be prepared by reacting free acid forms of these compounds with a stoichiometric amount of the appropriate base (such as Na, Ca, Mg, or K hydroxide, carbonate, bicarbonate, or the like), or by reacting free base forms of these compounds with a stoichiometric amount of the appropriate acid. Such reactions are typically carried out in water or in an organic solvent, or in a mixture of the two. Generally, non-aqueous media like ether, ethyl acetate, ethanol, isopropanol, or acetonitrile are typical, where practicable. Salts of the present compounds further include solvates of the compounds and of the compound salts. Examples of pharmaceutically acceptable salts include, but are not limited to, mineral or organic acid salts of basic residues such as amines; alkali or organic salts of acidic residues such as carboxylic acids; and the like. The pharmaceutically acceptable salts include the conventional non-toxic salts and the quaternary ammonium salts of the parent compound formed, for example, from non-toxic inorganic or organic acids. For example, conventional non-toxic acid salts include those derived from inorganic acids such as hydrochloric, hydrobromic, sulfuric, sulfamic, phosphoric, nitric and the like; and the salts prepared from organic acids such as acetic, propionic, succinic, glycolic, stearic, lactic, malic, tartaric, citric, ascorbic, pamoic, maleic, hydroxymaleic, phenylacetic, glutamic, benzoic, salicylic, mesylic, esylic, besylic, sulfanilic, 2-acetoxybenzoic, fumaric, toluenesulfonic, methanesulfonic, ethane disulfonic, oxalic, isethionic, HOOC-(CHz)n- COOH where n is 0-4, and the like, or using a different acid that produces the same counterion. Lists of additional suitable salts may be found, e.g., in Remington's Pharmaceutical Sciences, 17th ed., Mack Publishing Company, Easton, Pa., p. 1418 (1985). The term “carrier” means a diluent, excipient, or vehicle that an active agent is used or delivered in. A “pharmaceutically acceptable excipient” means an excipient that is useful in preparing a pharmaceutical composition / combination that is generally safe, and neither biologically nor otherwise inappropriate for administration to a host, typically a human. In certain embodiments, an excipient is used that is acceptable for veterinary use. A “patient” or “host” is a human or non-human animal in need of treatment, of any of the disorders as specifically described herein. Typically, the host is a human. A “host” may alternatively refer to for example, a mammal, primate (e.g., human), cow, sheep, goat, horse, dog, cat, rabbit, rat, mice, fish, bird and the like. A “therapeutically effective amount” of a pharmaceutical composition / combination of this invention means an amount effective, when administered to a host, to provide a therapeutic benefit such as an amelioration of symptoms or reduction or diminution of the disease itself. II. Compounds of the present invention In certain embodiments, the compound used in the present invention is =o o ® N: >= 0 li Co 0 oo lv acceptable salt thereof nN | ! uv 0 SAA (Compound 1) or a pharmaceutically acceptable salt thereof. In certain embodiments, the compound used in the present invention is =0 A J—NH Oo A (Compound 2) or a pharmaceutically acceptable salt thereof. 0 y (x ES NN 2) J tically acceptable salt thereof. In certain embodiments, the compound used in the present invention is =0 fi NH oO NF (Compound 3) or a pharmaceutically acceptable salt thereof. 0 - For rr or utically acceptable salt thereof. In certain embodiments, the compound used in the present invention is =0 + NH Jr or NC F 0 ora “F NC” ~~ °F (Compound 4) or a pharmaceutically acceptable salt thereof. In certain embodiments, the compound used in the present invention is =0 A NH J ~ ; ! ! © ov SANS (Compound 5) or a pharmaceutically acceptable salt thereof. o (- 20 4 lly acceptable salt thereof. In certain embodiments, the compound used in the present invention is =o 7 J—NH 0 o x N— Nes J NYA = 0 \N— ceptable salt thereof. 0 oo (Compound 6) or a pharmaceutically acceptable salt thereof. In certain embodiments, the compound used in the present invention is =0 ho J—NH Oo 0 (- Na LOO) 4 cally acceptable salt thereof. NT (Compound 7) or a pharmaceutically acceptable salt thereof. In certain embodiments, the compound used in the present invention is =0 ya NH Jr NNT - (Compound 8) or a pharmaceutically acceptable salt thereof. Oo Co- N= Oe I 4 ically acceptable salt thereof. In certain embodiments, the compound used in the present invention is =0 LA NH J NT - (Compound 9) or a pharmaceutically acceptable salt thereof. oO 0 AL) ~ ) J cally acceptable salt thereof. In certain embodiments, the compound used in the present invention is =0 i J—NH oO AY NT (Compound 10) or a pharmaceutically acceptable salt thereof. 0 w CO NA = ] J Nt cceptable salt thereof. In certain embodiments, the compound used in the present invention is SRE WIRES TRIE MIO MARIA IA MEAs 20 Mae pave o Qa N NH OAT [0] iticallv acceptable salt thereof. 0 To (Compound 11) or a pharmaceutically acceptable salt thereof. In certain embodiments, the compound used in the present invention is =0 oro I g 5 Xi J A (Compound 12) or a pharmaceutically acceptable salt thereof. In certain embodiments, the compound used in the present invention is F 0 J N— =o hk J—NH Oo NT - (Compound 13) or a pharmaceutically acceptable salt thereof, Oo Loan MOOT tically acceptable salt thereof. 111. Embodiments of the Present Invention. 1. In certain embodiments, the invention provides a treatment of an Ikaros or Aiolos mediated disorder comprising administering a low dose treatment regimen in a host in need thereof comprising administering a dose of not more than about 500, 450, 400, 350, 300, 250 200, 150 or even 100 micrograms (ug) once a day (QD) or twice a day (BID) of a compound selected from Compound 1, Compound 2, Compound 3, Compound 4, Compound 5, Compound 6, Compound 7, Compound 8, Compound 9, Compound 10, Compound 11, Compound 12, or Compound 13 or a pharmaceutically acceptable salt thereof. 2. The treatment of embodiment 1 wherein the treatment regimen includes a drug holiday. 3. The treatment of embodiment 2 wherein the drug holiday is accomplished with a regimen of therapy once or twice a day for at least 13, 14 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26 or 27 continuous days, and then a holiday taken until the next 28 day cycle. 4, The treatment of embodiment 3 wherein therapy is given once or twice a day for 21 days followed by a 7 day holiday. 5. The treatment of any one of embodiments 1-4, wherein the dose is less than about 400 pg. 6. The treatment of any one of embodiments 1-4, wherein the dose is less than about 300 pg. 7. The treatment of any one of embodiments 1-4, wherein the dose is less than about 200 pg. 8. The treatment of any one of embodiments 1-4, wherein the dose is less than about 100 pg. 9. The treatment of any one of embodiments 1-4, wherein the dose is less than about 50 or 25 Ug. 10. The treatment of any one of embodiments 1-9, wherein the Ikaros or Aiolos mediated disorder is a diffuse large B-cell lymphoma. 11. The treatment of embodiment 10, wherein the diffuse large B-cell lymphoma is an activated B-cell lymphoma. 12. The treatment of embodiment 10, wherein the diffuse large B-cell lymphoma is a germinal center B-cell lymphoma. 13. The treatment of embodiment 1-9, wherein the Ikaros or Aiolos mediated disorder is a anaplastic large cell lymphoma. 14. The treatment of any one of embodiments 1-9, wherein the Ikaros or Aiolos mediated disorder is a cutaneous T-cell lymphoma. 15. The treatment of any one of embodiments 1-9, wherein the Ikaros or Aiolos mediated disorder is mantle cell lymphoma. 16. The treatment of any one of embodiments 1-9, wherein the Ikaros or Aiolos mediated disorder is a multiple myeloma. 17. The treatment of any one of embodiments 1-16, wherein the disorder is resistant to treatment with first generation IMiD drugs. 18. The treatment of embodiments 17, wherein the disorder is resistant to treatment with thalidomide. 19. The treatment of embodiment 17, wherein the disorder is resistant to treatment with pomalidomide. 20. The treatment of embodiment 17, wherein the disorder is resistant to treatment with lenalidomide. 21. The treatment of embodiment 17, wherein the disorder is resistant to treatment with iberdomide. 22. A treatment of a disorder mediated by Ikaros (IKZF1) and / or Aiolos (IKZF3) wherein a blood or tissue sample is taken from the patient and the concentration of one or more biomarkers, for example IRF-1, caspase-3, IL-2, and / or IFN-y, is determined, wherein if the patient has a statistically lower concentration including but not limited to up to about 5, 10, 15 or 20% lower, of the biomarker than a healthy person then Compound 1 or a pharmaceutically acceptable salt thereof or another compound described herein is administered to the patient. 23. A treatment of a disorder mediated by Ikaros (IKZF1) and / or Aiolos (IKZF3) wherein a blood or tissue sample is taken from the patient and the concentration of one or more biomarkers, for example cyclin D1, E2F1, ZFP91, SALL4, IRF-4, BLIMP1, and / or MYC is determined, wherein if the patient has a statistically higher concentration including but not limited to up to about 5, 10, 15 or 20% higher of biomarker than a healthy person then Compound 1 or a pharmaceutically acceptable salt thereof or another compound described herein is administered to the patient. 24. A treatment of a disorder mediated by Ikaros (IKZF1) and / or Aiolos (IKZF3) wherein the patient is administered Compound 1 or a pharmaceutically acceptable salt thereof or another compound described herein and then a blood or tissue sample is taken from the patient and the concentration of one or more biomarkers, for example IRF-1, caspase-3, IL-2, and / or IFN-y, is determined, wherein if the concentration of the biomarker is not significantly increased, for example by at least about 1.25, 1.5, 1.75, or 2-fold, then the dose of the compound is increased. 25. A treatment of a disorder mediated by Ikaros (IKZF1) and / or Aiolos (IKZF3) wherein the patient is administered Compound 1 or a pharmaceutically acceptable salt thereof or another compound described herein and then a blood or tissue sample is taken from the patient and the concentration of one or more biomarkers, for example cyclin D1, E2F1, ZFP91, SALL4, IRF-4, BLIMP1, and / or MYC is determined, wherein if the concentration of the biomarker is not significantly decreased, for example by at least about 1.25, 1.5, 1.75, or 2-fold, then the dose of the compound is increased. 26. The treatment of any one of embodiments 22-25, wherein the dose is increased if the concentration of biomarker is less than 150%. 27. The treatment of any one of embodiments 22-25, wherein the dose is increased if the concentration of biomarker is less than 160%. 28. The treatment of any one of embodiments 22-25, wherein the dose is increased if the concentration of biomarker is less than 170%. 29. The treatment of any one of embodiments 22-25, wherein the dose is increased if the concentration of biomarker is less than 180%. 30. A treatment of an Ikaros or Aiolos mediated disorder comprising administering an effective amount of a compound selected from Compound 1, Compound 2, Compound 3, Compound 4, Compound 5, Compound 6, Compound 7, Compound 8, Compound 9, Compound 10, Compound 11, Compound 12, and Compound 13 or a pharmaceutically acceptable salt thereof, to a patient in need thereof, wherein the Ikaros or Aiolos mediated disorder is an activated diffuse large B-cell lymphoma or germinal center large B-cell lymphoma. 31. A treatment of a disorder mediated by Ikaros (IKZF1) and / or Aiolos (IKZF3) wherein a compound selected from Compound 1, Compound 2, Compound 3, Compound 4, Compound 5, Compound 6, Compound 7, Compound 8, Compound 9, Compound 10, Compound 11, Compound 12, and Compound 13, or a pharmaceutically acceptable salt thereof, is used in combination with a BTK inhibitor selected from acalabrutinib, spebrutinib, zanubrutinib, 1L.OXO0-3035, evobrutinib, TG-1701, tolebrutinib, BIIB091, DZD-9008, HZ-A-018, orelabrutinib, AC0058TA, SN1011, rilzabrutinib, ARQ 531, DTRMWXHS-12, INJ-64264681, branebrutinib, and fenebrutinib. 32. A treatment of a disorder mediated by Ikaros (IKZF1) and / or Aiolos (IKZF3) wherein a compound selected from Compound 1, Compound 2, Compound 3, Compound 4, Compound 5, Compound 6, Compound 7, Compound 8, Compound 9, Compound 10, Compound 11, Compound 12, and Compound 13 or a pharmaceutically acceptable salt thereof, is used in combination with a CD38 antibody selected from felzartamab, GBR 1342, TAK-573, CID-103, OKT10, STI-6129, SGX301, TAK-079, and mezagitamab. 33. A treatment of a disorder mediated by Ikaros (IKZF1) and / or Aiolos (IKZF3) wherein a compound selected from Compound 1, Compound 2, Compound 3, Compound 4, Compound 5, Compound 6, Compound 7, Compound 8, Compound 9, Compound 10, Compound 11, Compound 12, and Compound 13 or a pharmaceutically acceptable salt thereof, is used in combination with a proteasome inhibitor selected from ixazomib citrate, oprozomib, delanzomib, lactacystin, epoxomicin, MGI32, MG-262, CEP-18770, NEOSHI101, TQB3602, and KZR-616. 34. A treatment of a disorder mediated by Ikaros (IKZF1) and / or Aiolos (IKZF3) wherein a compound selected from Compound 1, Compound 2, Compound 3, Compound 4, Compound 5, Compound 6, Compound 7, Compound 8, Compound 9, Compound 10, Compound 11, Compound 12, and Compound 13 or a pharmaceutically acceptable salt thereof, is used in combination with an IMiD selected from CC-92480, CC-90009, and CC-99282 35. A treatment of a disorder mediated by Ikaros (IKZF1) and / or Aiolos (IKZF3) wherein a compound selected from Compound 1, Compound 2, Compound 3, Compound 4, Compound 5, Compound 6, Compound 7, Compound 8, Compound 9, Compound 10, Compound 11, Compound 12, and Compound 13 or a pharmaceutically acceptable salt thereof, is used in combination with a HDAC inhibitor selected from trapoxin B, sodium phenylbutyrate, tacedinaline, mocetinostat, BRD73954, BG45, domatinostat, cay10603, HPOB, TMP269, nexturastat A, Santacruzamate A, splitomicin, LMK-235, sodium butyrate, pivaloyloxymethyl butyrate, pyroxamide, abexinostat, resminostat, givinostat, quisinostat, Psammaplin A, KD5170, 1-Alaninechlamydocin, depudecin, and CUDC-101. 36. A treatment of a disorder mediated by Ikaros (IKZF1) and / or Aiolos (IKZF3) wherein a compound selected from Compound 1, Compound 2, Compound 3, Compound 4, Compound 5, Compound 6, Compound 7, Compound 8, Compound 9, Compound 10, Compound 11, Compound 12, and Compound 13 or a pharmaceutically acceptable salt thereof, is used in combination with a compound selected from selinexor, oxaphenamide, belantamab mafodotin, denosumab, zoledronic acid, plerixafor, eltrombopag, ipilumumab, palbociclib, ricolinostat, afuresertib, dinaciclib, filanesib, indatuximab ravtansine, masitinib, sonidegib, sotatercept, ulocuplumab, and urelumab. 37. The treatment of any one of embodiments 1-36, wherein the compound is =o Oo Cl = 0 yw I | 0 o_~ tically acceptable salt thereof 3 ; ! ! v 0 SAY (Compound 1) or a pharmaceutically acceptable salt thereof. 38. The treatment of any one of embodiments 1-36, wherein the compound is =o Ha J—NH oO NT (Compound 2) or a pharmaceutically acceptable salt thereof. O wo C= AI 4 ceutically acceptable salt thereof. 39. The treatment of any one of embodiments 1-36, wherein the compound is =0 fi J—NH 0 0 N— F MN 3 rr or ¢ onion runs ks em ler marsovctalo watt tharnmat NF (Compound 3) or a pharmaceutically acceptable salt thereof, 40. The treatment of any one of embodiments 1-36, wherein the compound is =0 i J—NH oO or NC F Qo ora Sy “F NC” ~~ °F (Compound 4) or a pharmaceutically acceptable salt thereof. 41. The treatment of any one of embodiments 1-36, wherein the compound is =o & J—NH Oo ® ; ! ! ov oOo SANS (Compound 5) or a pharmaceutically acceptable salt thereof. o CO- ood 4 tically acceptable salt thereof. 42. The treatment of any one of embodiments 1-36, wherein the compound is =0 A J—NH Oo o x N— Na ) NOY = o Nf v acceptable salt thereof o To (Compound 6) or a pharmaceutically acceptable salt thereof, 43, The treatment of any one of embodiments 1-36, wherein the compound is =o rr A J—NH oO o vw, CO LO XY 4 eutically acceptable salt thereof. NT (Compound 7) or a pharmaceutically acceptable salt thereof. 44. The treatment of any one of embodiments 1-36, wherein the compound is =o £ NH J NNT - (Compound 8) or a pharmaceutically acceptable salt thereof, Oo w C- Oa 4 eutically acceptable salt thereof. 45. The treatment of any one of embodiments 1-36, wherein the compound is =0 & NH J NT - (Compound 9) or a pharmaceutically acceptable salt thereof. oO N Cl N— AOE? eutically acceptable salt thereof. 46. The treatment of any one of embodiments 1-36, wherein the compound is =0 i J—NH Oo AY NT (Compound 10) or a pharmaceutically acceptable salt thereof. Oo AN \ N— OY = & Nd ly acceptable salt thereof. 47. The treatment of any one of embodiments 1-36, wherein the compound is wiih MLA) MR UE RIVA AIA RS BAR, ARATE AAR AAT O <r vo, QO {Orie ° o wceuticallv acceptable salt thereof. oO oo (Compound 11) or a pharmaceutically acceptable salt thereof. 48. The treatment of any one of embodiments 1-36, wherein the compound is =0 ora oO NN (Compound 12) or a pharmaceutically acceptable salt thereof. 49, The treatment of any one of embodiments 1-36, wherein the compound is F UL J N= =o i J—NH Oo NT (Compound 13) or a pharmaceutically acceptable salt thereof. Oo F Cl N= A y N N o iceutically acceptable salt thereof. 50. The treatment of any one of embodiments 1-49, wherein the compound is administered in combination with a Bruton tyrosine kinase inhibitor. 51. The treatment of embodiment 50, wherein the Bruton tyrosine kinase inhibitor is ibrutinib. 52. The treatment of any one of embodiments 1-49, wherein the compound is administered in combination with a corticosteroid. 53. The treatment of embodiment 52, wherein the corticosteroid is dexamethasone. 54. The treatment of any one of embodiments 1-49, wherein the compound is administered in conjunction with CAR T-cell therapy. 55. The treatment of any one of embodiments 1-49, wherein the compound is administered in conjunction with an antibody-drug conjugate. 56. The treatment of any one of embodiments 1-49, wherein the compound is administered in conjunction with BiTE therapy. 57. The treatment of any one of embodiments 1-49, wherein the compound is administered in conjunction with a bispecific antibody. 58. The treatment of any one of embodiments 1-49, wherein the compound is administered in conjunction with a monoclonal antibody. 59. The treatment of any one of embodiments 1-49, wherein the compound is administered in conjunction with a BTK inhibitor selected from acalabrutinib, spebrutinib, zanubrutinib, LOX0-305, evobrutinib, TG-1701, tolebratinib, BIIB091, DZD-9008, HZ-A-018, orelabrutinib, ACO058TA, SN1011, rilzabrutinib, ARQ 531, DTRMWXHS-12, JNJ- 64264681, branebrutinib, ibrutinib, and fenebrutinib. 60. The treatment of any one of embodiments 1-49, wherein the compound is administered in conjunction with a CD38 antibody selected from felzartamab, daratumumab, GBR 1342, TAK-573, CID-103, OKT10, STI-6129, SGX301, TAK-079, and mezagitamab. 61. The treatment of any one of embodiments 1-49, wherein the compound is administered in conjunction with a proteasome inhibitor selected from ixazomib citrate, oprozomib, delanzomib, lactacystin, bortezomib, carfilzomib, VLX1570, epoxomicin, MG132, MG- 262, CEP-18770, NEOSH101, TQB3602, and KZR-616. 62. The treatment of any one of embodiments 1-49, wherein the compound is administered in conjunction with an IMiD selected from pomalidomide, lenalidomide, thalidomide, iberdomide CC-92480, CC-90009, and CC-99282. 63. The treatment of any one of embodiments 1-49, wherein the compound is administered in conjunction with an HDAC inhibitor selected from trapoxin B, sodium phenylbutyrate, tacedinaline, mocetinostat, BRD73954, BG45, domatinostat, cay 10603, HPOB, TMP269, nexturastat A, Santacruzamate A, splitomicin, LMK-235, sodium butyrate, pivaloyloxymethyl butyrate, pyroxamide, abexinostat, resminostat, givinostat, quisinostat, Psammaplin A, KD5170, 1-Alaninechlamydocin, depudecin, and CUDC-101. 64. The treatment of any one of embodiments 1-49, wherein the compound is administered in conjunction with a compound selected from selinexor, oxaphenamide, belantamab mafodotin, denosumab, zoledronic acid, plerixafor, eltrombopag, ipilumumab, palbociclib, ricolinostat, afuresertib, dinaciclib, filanesib, indatuximab ravtansine, masitinib, sonidegib, sotatercept, ulocuplumab, and urelumab. In certain embodiments a treatment is provided as described above wherein the dose of Compound 1 is less than or equal to about 5 ug. In certain embodiments a treatment is provided as described above wherein the dose of Compound 1 is less than or equal to about 10 pg. ‘Additional Embodiments 1. In certain embodiments a method of treating a disorder mediated by Ikaros and / or Aiolos comprising administering a dose of no more than about 500 micrograms (pg) once a day (QD) or twice a day (BID) of a compound selected from =o nN ! bv 0’ SAY (Compound 1) o Ci TA a | 0 oo 0 =0 A J—NH 0 (Compound 2) 0 ww C0 AHS 2) J Noid =0 A NH oO (Compound 3) 0 N— For J rr oOo ’ 0 i »=0 5 NH Jr or NC F 0o J COX NN “F (Compound 4) =0 A J—NH Oo ~ | 0 SAS (Compound 5) oO CO- 20d oo op =o NH a (Compound 6) oO A N— » Na NYA = o rt 0 =u i J—NH Oo (Compound 7) O in "J 0 =0 FI A J—NH oO (Compound 8) 0 x A N— MOBI 4 0 =0 i J—NH Oo (Compound 9) 0 CO AE ) J =0 i J—NH oO (Compound 10) AY (Compound 11) oa =0 (Compound 12) 0 I J 5 5% d NH F LJ N= =O i NH J Nt Md - (Compound 13) or a pharmaceutically acceptable salt thereof, is provided. 0 ry C15 ANH = J J rmaceutically acceptable salt thereof, is | 2. The method of embodiment 1, wherein the compound is administered at a dose between about 500 micrograms and 1 microgram. 3. The method of embodiment 1 or embodiment 2, wherein the compound is administered for multiple days with a drug holiday in between subsequent treatment cycles. 4. The method of embodiment 3, wherein the compound is administered once or twice a day for at least 13, 14 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26 or 27 continuous days, and then the drug holiday is taken until the next 28-day cycle. 5. The method of embodiment 3, wherein the compound is administered once or twice a day for 21 days followed by a 7-day holiday. 6. The method of any one of embodiments 1-5, wherein the dose is less than or equal to about 400 ug. 7. The method of any one of embodiments 1-5, wherein the dose is less than or equal to about 300 ug. 8. The method of any one of embodiments 1-5, wherein the dose is less than or equal to about 200 ug. 9. The method of any one of embodiments 1-5, wherein the dose is less than or equal to about 100 pg. 10. The method of any one of embodiments 1-5, wherein the dose is less than or equal to about 50 pug. 11. The method of any one of embodiments 1-5, wherein the dose is less than or equal to about 25 ug. 12. The method of any one of embodiments 1-5, wherein the dose is less than or equal to about 10 pg. 13. The method of any one of embodiments 1-5, wherein the dose is less than or equal to about 5 ug. 14. The method of any one of embodiments 1-5, wherein the dose is about 50 pg. 15. The method of any one of embodiments 1-5, wherein the dose is about 25 pg. 16. The method of any one of embodiments 1-5, wherein the dose is about 10 pg. 17. The method of any one of embodiments 1-5, wherein the dose is about 5 pg. 18. The method of any one of embodiments 1-17, wherein the disorder is a diffuse large B-cell lymphoma. 19. The method of embodiment 18, wherein the diffuse large B-cell lymphoma is an activated B-cell lymphoma, 20. The method of embodiment 18, wherein the diffuse large B-cell lymphoma is a germinal center B-cell lymphoma. 21. The method of any one of embodiments 1-17, wherein the disorder is an anaplastic large cell lymphoma. 22. The method of any one of embodiments 1-17, wherein the disorder is a cutaneous T-cell lymphoma. 23. The method of any one of embodiments 1-17, wherein the disorder is mantle cell lymphoma. 24. The method of any one of embodiments 1-17, wherein the disorder is multiple myeloma. 25. The method of any one of embodiments 1-24, wherein the disorder is resistant to treatment with first generation IMiD drugs. 26. The method of embodiment 25, wherein the disorder is resistant to treatment with thalidomide. 27. The method of embodiment 25, wherein the disorder is resistant to treatment with pomalidomide. 28. The method of embodiment 25, wherein the disorder is resistant to treatment with lenalidomide. 29. The method of embodiment 25, wherein the disorder is resistant to treatment with iberdomide. 30. In certain embodiments a method of treating a disorder mediated by Ikaros (IKZF1) and / or Aiolos (IKZF3) wherein a blood or tissue sample is taken from a patient and the concentration of one or more biomarkers selected from IRF-1, caspase-3, IL-2, and IFN- v, is determined, wherein if the patient has a statistically lower concentration of the biomarker(s) than a healthy person then a compound selected from Compound 1, Compound 2, Compound 3, Compound 4, Compound 5, Compound 6, Compound 7, Compound 8, Compound 9, Compound 10, Compound 11, Compound 12, and Compound 13, or a pharmaceutically acceptable salt thereof is administered to the patient, is provided. 31. The method of embodiment 30, wherein the statistically lower concentration of the biomarker(s) is 5% lower than an average healthy patient. 32. The method of embodiment 30, wherein the statistically lower concentration of the biomarker(s) is 20% lower than an average healthy patient. 33. A method of treating a disorder mediated by Ikaros (IKZF1) and / or Aiolos (IKZF3) wherein a blood or tissue sample is taken from a patient and the concentration of one or more biomarkers selected from cyclin D1, E2F1, ZFP91, SALL4, IRF-4, BLIMP1, and MYC is determined, wherein if the patient has a statistically higher concentration of the biomarker(s) than a healthy person then a compound selected Compound 1, Compound 2, Compound 3, Compound 4, Compound 5, Compound 6, Compound 7, Compound 8, Compound 9, Compound 10, Compound 11, Compound 12, and Compound 13, or a pharmaceutically acceptable salt thereof is administered to the patient. 34. The method of embodiment 33, wherein the statistically higher concentration of the biomarker(s) is 5% higher than an average healthy patient. 35. The method of embodiment 33, wherein the statistically higher concentration of the biomarker(s) is 20% higher than an average healthy patient. 36. In certain embodiments a method of treating a disorder mediated by Ikaros (IKZF1) and / or Aiolos (IKZF3) wherein a patient is administered a compound selected from Compound 1, Compound 2, Compound 3, Compound 4, Compound 5, Compound 6, Compound 7, Compound 8, Compound 9, Compound 10, Compound 11, Compound 12, and Compound 13, or a pharmaceutically acceptable salt thereof, and then a blood or tissue sample is taken from the patient and the concentration of one or more biomarkers selected from IRF-1, caspase-3, IL-2, and IFN-y, is determined, wherein if the concentration of the biomarker(s) is not significantly increased, then the dose of the compound is increased, is provided. 37. The method of embodiment 36, wherein the dose of the compound is increased if the concentration of the biomarkers(s) is not increased by at least about 25%. 38. The method of embodiment 36, wherein the dose of the compound is increased if the concentration of the biomarkers(s) is not increased by at least about 100%. 39. The method of embodiment 36, wherein the dose of the compound is increased if the concentration of the biomarkers(s) is not increased by at least about 200%. 40. In certain embodiments a method of treating a disorder mediated by Ikaros (IKZF1) and / or Aiolos (IKZF3) wherein a patient is administered a compound selected from Compound 1, Compound 2, Compound 3, Compound 4, Compound 5, Compound 6, Compound 7, Compound 8, Compound 9, Compound 10, Compound 11, Compound 12, and Compound 13, or a pharmaceutically acceptable salt thereof, and then a blood or tissue sample is taken from the patient and the concentration of one or more biomarkers selected from cyclin D1, E2F1, ZFP91, SALL4, IRF-4, BLIMP1, and MYC is determined, wherein if the concentration of the biomarker(s) is not significantly decreased, then the dose of the compound is increased, is provided. 41. The method of embodiment 40, wherein the dose of the compound is increased if the concentration of the biomarkers(s) is not decreased by at least about 10%. 42. The method of embodiment 40, wherein the dose of the compound is increased if the concentration of the biomarkers(s) is not decreased by at least about 25%. 43. The method of embodiment 40, wherein the dose of the compound is increased if the concentration of the biomarkers(s) is not decreased by at least about 50%. 44. In certain embodiments a method of treating a disorder mediated by Ikaros and / or Aiolos comprising administering an effective amount of a compound selected from Compound 1, Compound 2, Compound 3, Compound 4, Compound 5, Compound 6, Compound 7, Compound 8, Compound 9, Compound 10, Compound 11, Compound 12, and Compound 13 or a pharmaceutically acceptable salt thereof, to a patient in need thereof, wherein the Ikaros or Aiolos mediated disorder is an activated diffuse large B-cell lymphoma or germinal center large B-cell lymphoma, is provided. 45. In certain embodiments a method of treating a disorder mediated by Ikaros and / or Aiolos comprising administering an effective amount of a compound selected from Compound 1, Compound 2, Compound 3, Compound 4, Compound 5, Compound 6, Compound 7, Compound 8, Compound 9, Compound 10, Compound 11, Compound 12, and Compound 13, or a pharmaceutically acceptable salt thereof, wherein the patient also receives a BTK inhibitor selected from acalabrutinib, spebrutinib, zanubrutinib, LOX0-303, evobrutinib, TG-1701, tolebrutinib, BIIBO91, DZD-9008, HZ-A-018, orelabrutinib, ACO0058TA, SN1011, rilzabrutinib, ARQ 531, DTRMWXHS-12, INJ-64264681, branebrutinib, and fenebrutinib, is provided. 46. In certain embodiments a method of treating a disorder mediated by Ikaros and / or Aiolos comprising administering an effective amount of a compound selected from Compound 1, Compound 2, Compound 3, Compound 4, Compound 5, Compound 6, Compound 7, Compound 8, Compound 9, Compound 10, Compound 11, Compound 12, and Compound 13 or a pharmaceutically acceptable salt thereof, wherein the patient also receives a CD38 antibody selected from felzartamab, GBR 1342, TAK-573, CID-103, OKT10, STI-6129, SGX301, TAK-079, and mezagitamab, is provided. 47. In certain embodiments a method of treating a disorder mediated by Ikaros and / or Aiolos comprising administering an effective amount of a compound selected from Compound 1, Compound 2, Compound 3, Compound 4, Compound 5, Compound 6, Compound 7, Compound 8, Compound 9, Compound 10, Compound 11, Compound 12, and Compound 13 or a pharmaceutically acceptable salt thereof, wherein the patient also receives a proteasome inhibitor selected from ixazomib citrate, oprozomib, delanzomib, lactacystin, epoxomicin, MG132, MG-262, CEP-18770, NEOSH101, TQB3602, and KZR-616, is provided. 48. In certain embodiments a method of treating a disorder mediated by Ikaros and / or Aiolos comprising administering an effective amount of a compound selected from Compound 1, Compound 2, Compound 3, Compound 4, Compound 5, Compound 6, Compound 7, Compound 8, Compound 9, Compound 10, Compound 11, Compound 12, and Compound 13 or a pharmaceutically acceptable salt thereof, to a patient in need thereof, wherein the patient also receives an IMiD selected from CC-92480, C(C-90009, and CC-99282, is provided. 49. In certain embodiments a method of treating a disorder mediated by Ikaros and / or Aiolos comprising administering an effective amount of a compound selected from Compound 1, Compound 2, Compound 3, Compound 4, Compound 5, Compound 6, Compound 7, Compound 8, Compound 9, Compound 10, Compound 11, Compound 12, and Compound 13 or a pharmaceutically acceptable salt thereof, to a patient in need thereof, wherein the patient also receives a HDAC inhibitor selected from trapoxin B, sodium phenylbutyrate, tacedinaline, mocetinostat, BRD73954, BG45, domatinostat, cay10603, HPOB, TMP269, nexturastat A, Santacruzamate A, splitomicin, LMK-235, sodium butyrate, pivaloyloxymethyl butyrate, pyroxamide, abexinostat, resminostat, givinostat, quisinostat, Psammaplin A, KD5170, 1-Alaninechlamydocin, depudecin, and CUDC-101, is provided. 50. In certain embodiments a method of treating a disorder mediated by Ikaros and / or Aiolos comprising administering an effective amount of a compound selected from Compound 1, Compound 2, Compound 3, Compound 4, Compound 5, Compound 6, Compound 7, Compound 8, Compound 9, Compound 10, Compound 11, Compound 12, and Compound 13 or a pharmaceutically acceptable salt thereof, to a patient in need thereof, wherein the patient also receives a compound selected from selinexor, oxaphenamide, belantamab mafodotin, denosumab, zoledronic acid, plerixafor, eltrombopag, ipilumumab, palbociclib, ricolinostat, afuresertib, dinaciclib, filanesib, indatuximab ravtansine, masitinib, sonidegib, sotatercept, ulocuplumab, and urelumab, is provided. 51. The method of any one of embodiments 1-50, wherein the compound is =0 o C= 0 = Lo J o_ tically acceptable salt thereof No ! J v os SN (Compound 1) or a pharmaceutically acceptable salt thereof. 52. The method of any one of embodiments 1-50, wherein the compound is =o i J—NH oO NT (Compound 2) or a pharmaceutically acceptable salt thereof. Oo ww CO AI 4 ceutically acceptable salt thereof. 53. The method of any one of embodiments 1-50, wherein the compound is =0 i NH oO o N— F Mn a r or : eae aq aa a NF (Compound 3) or a pharmaceutically acceptable salt thereof, 54. The method of any one of embodiments 1-50, wherein the compound is =0 NH Jr NA NC” C _ 0 + OX Ys “F NC” ~~ °F (Compound 4) or a pharmaceutically acceptable salt thereof. 55. The method of any one of embodiments 1-50, wherein the compound is =0 NH J No } ! © oo A Sa (Compound S) or a pharmaceutically acceptable salt thereof, oO (O- TAT 4 tically acceptable salt thereof. 56. The method of any one of embodiments 1-50, wherein the compound is =o A J—NH oO o A N— Ne J NY = o Nd v acceptable salt thereof o To (Compound 6) or a pharmaceutically acceptable salt thereof. 57. The method of any one of embodiments 1-50, wherein the compound is =o A J—NH oO o vw CO LO-a XY 4 eutically acceptable salt thereof. NT (Compound 7) or a pharmaceutically acceptable salt thereof. 58. The method of any one of embodiments 1-50, wherein the compound is =0 i NH J NNT (Compound 8) or a pharmaceutically acceptable salt thereof. 0o (O- ES Oa 4 eutically acceptable salt thereof. 59. The method of any one of embodiments 1-50, wherein the compound is =0 fo J—NH 0 A) NN 7 B (Compound 9) or a pharmaceutically acceptable salt thereof. 60. The method of any one of embodiments 1-50, wherein the compound is ¥=0 NH J AY NN 7 B (Compound 10) or a pharmaceutically acceptable salt thereof. Oo NR NH 2 ig & ly acceptable salt thereof. 61. The method of any one of embodiments 1-50, wherein the compound is iA WA WE Ce LUM EH we LT My EL Mel TL A oO N TT) N. NH OK 2 % | o 0 aceuticallv acceptable salt thereof 0 oo (Compound 11) or a pharmaceutically acceptable salt thereof. 62. The method of any one of embodiments 1-50, wherein the compound is =o A (Compound 12) or a pharmaceutically acceptable salt thereof, 63. The method of any one of embodiments 1-50, wherein the compound is F LJ N— =o ih NH J Xy NT B (Compound 13) or a pharmaceutically acceptable salt thereof, 64. The method of any one of embodiments 1-63, wherein a Bruton tyrosine kinase inhibitor is also administered to the patient. 65. The method of embodiment 64, wherein the Bruton tyrosine kinase inhibitor is ibrutinib. 66. The method of any one of embodiments 1-65, wherein a corticosteroid is also administered to the patient. 67. The method of embodiment 66, wherein the corticosteroid is dexamethasone. 68. The method of any one of embodiments 1-67, wherein CAR T-cell therapy is also administered to the patient. 69. The method of any one of embodiments 1-67, wherein an antibody-drug conjugate is also administered to the patient. 70. The method of any one of embodiments 1-67, wherein BiTE therapy is also administered to the patient. 71. The method of any one of embodiments 1-67, wherein a bispecific antibody is also administered to the patient. 72. The method of any one of embodiments 1-67, wherein a monoclonal antibody is also administered to the patient. 73. The method of any one of embodiments 1-67, wherein a BTK inhibitor selected from acalabrutinib, spebrutinib, zanubrutinib, LOX0-305, evobrutinib, TG-1701, tolebrutinib, BIIB091, DZD-9008, HZ-A-018, orelabrutinib, ACO058TA, SN1011, rilzabrutinib, ARQ 531, DTRMWXHS-12, INJ-64264681, branebrutinib, ibrutinib, and fenebrutinib is also administered to the patient. 74. The method of any one of embodiments 1-67, wherein a CD38 antibody selected from felzartamab, daratumumab, GBR 1342, TAK-573, CID-103, OKT10, STI-6129, SGX301, TAK-079, and mezagitamab is also administered to the patient. 75. The method of any one of embodiments 1-67, wherein a proteasome inhibitor selected from ixazomib citrate, oprozomib, delanzomib, lactacystin, bortezomib, carfilzomib, VL.X1570, epoxomicin, MG132, MG-262, CEP-18770, NEOSH101, TQB3602, and KZR-616 is also administered to the patient. 76. The method of any one of embodiments 1-67, wherein an IMiD selected from pomalidomide, lenalidomide, thalidomide, iberdomide CC-92480, CC-90009, and CC- 99282 is also administered to the patient. 77. The method of any one of embodiments 1-67, wherein an HDAC inhibitor selected from trapoxin B, sodium phenylbutyrate, tacedinaline, mocetinostat, BRD73954, BG45, domatinostat, cay 10603, HPOB, TMP269, nexturastat A, Santacruzamate A, splitomicin, LMK-235, sodium butyrate, pivaloyloxymethyl butyrate, pyroxamide, abexinostat, resminostat, givinostat, quisinostat, Psammaplin A, KD5170, 1-Alaninechlamydocin, depudecin, and CUDC-101 is also administered to the patient. 78. The method of any one of embodiments 1-67, wherein a compound selected from selinexor, oxaphenamide, belantamab mafodotin, denosumab, zoledronic acid, plerixafor, eltrombopag, ipilumumab, palbociclib, ricolinostat, afuresertib, dinaciclib, filanesib, indatuximab ravtansine, masitinib, sonidegib, sotatercept, ulocuplumab, and urelumab is also administered to the patient. 79. The method of any one of embodiments 1-78, wherein the compound selected from Compound 1, Compound 2, Compound 3, Compound 4, Compound 5, Compound 6, Compound 7, Compound 8, Compound 9, Compound 10, Compound 11, Compound 12, and Compound 13, or a pharmaceutically acceptable salt thereof is administered once a day. 80. The method of any one of embodiments 1-78, wherein the compound selected from Compound 1, Compound 2, Compound 3, Compound 4, Compound 5, Compound 6, Compound 7, Compound 8, Compound 9, Compound 10, Compound 11, Compound 12, and Compound 13, or a pharmaceutically acceptable salt thereof is administered twice a day. 81. The method of any one of embodiments 1-80, wherein the disorder is Non-Hodgkin's Lymphoma. 82. The method of any one of embodiments 1-80, wherein the disorder is Multiple Myeloma. 83. The method of any one of embodiments 1-82, wherein the disorder is relapsed. 84. The method of any one of embodiments 1-82, wherein the disorder is refractory. 85. The method of any one of embodiments 1-82, wherein the disorder is relapsed and refractory. IV. Treatment of Disorders Mediated by Ikaros and / or Aiolos Advantageous treatments of disorders mediated by Ikaros and / or Aiolos are provided. In certain embodiments, the treatment includes the administration of a low dosage form once or twice a day, optionally with a drug holiday, that are highly effective treatment modalities. For example, it has been discovered that treatment can be effective for a patient using one of the compounds described herein with a dosage of not more than about 500, 450, 400, 350, 325, 300, 275, 250, 225, 200, 175, 150, 125 or even 100, 75, 50 or 25 micrograms (ug) once a day (QD) or twice a day (BID) optionally with a treatment holiday. In some embodiments the patient is an adult (typically a human of at least 100 pounds or more, and typically 18 years old or more). In an alternative embodiment, the patient is pediatric (and may be less than 100 pounds and typically less than 18 years old). The selected compound, for example Compound 1 may be administered as monotherapy or may be combined with a standard of care therapy for the target tumor or cancer, including but not limited to any of those described in the Background of the Invention, or such as a proteasome inhibitor and / or an anti-CD38 monoclonal antibody (mAbs). In MCL, the selected compound can be used, for example, in combination with a Bruton tyrosine kinase (BTK) inhibitor, or an anti- CD20 monoclonal antibody. In PTCL, in particular ALCL, the selected compound may be administered, for example, in combination with anti-CD30 or anti-CD38 monoclonal antibody. In certain embodiments, Compound 1 is used to treat a disorder mediated by Ikaros or Aiolos according to a treatment regimen described herein. In certain embodiments, Compound 2 is used to treat a disorder mediated by Ikaros or Aiolos according to a treatment regimen described herein. In certain embodiments, Compound 3 is used to treat a disorder mediated by Ikaros or Aiolos according to a treatment regimen described herein. In certain embodiments, Compound 4 is used to treat a disorder mediated by Ikaros or Aiolos according to a treatment regimen described herein. In certain embodiments, Compound 5 is used to treat a disorder mediated by Ikaros or Aiolos according to a treatment regimen described herein. In certain embodiments, Compound 6 is used to treat a disorder mediated by Ikaros or Aiolos according to a treatment regimen described herein. In certain embodiments, Compound 7 is used to treat a disorder mediated by Ikaros or Aiolos according to a treatment regimen described herein. In certain embodiments, Compound 8 is used to treat a disorder mediated by Ikaros or Aiolos according to a treatment regimen described herein. In certain embodiments, Compound 9 is used to treat a disorder mediated by Ikaros or Aiolos according to a treatment regimen described herein. In certain embodiments, Compound 10 is used to treat a disorder mediated by Ikaros or Aiolos according to a treatment regimen described herein. In certain embodiments, Compound 11 is used to treat a disorder mediated by Ikaros or Aiolos according to a treatment regimen described herein. In certain embodiments, Compound 12 is used to treat a disorder mediated by Ikaros or Aiolos according to a treatment regimen described herein. In certain embodiments, Compound 13 is used to treat a disorder mediated by Ikaros or Aiolos according to a treatment regimen described herein. In certain embodiments a compound described herein, for example Compound 1, is used to treat a cancer that has metastasized. In certain embodiments a compound described herein, for example Compound 1, is used to treat a cancer that has metastasized to the brain. Treatment Cycles In certain embodiments, the dosage includes a drug holiday. A drug holiday is a time period during which the patient is not administered the active compound. For example, the patient may be administered the active compound or its pharmaceutically acceptable salt for 21 continuous days and not administered the chemotherapeutic for 7 days during a 28 day cycle, and then optionally the regimen is repeated once, several or mor times. In certain examples, one of the compounds described herein may be administered once or twice a day for at least 18, 19, 20, 21, 22,23, 24, 25, 26 or 27 continuous days, and then a holiday taken until the next 28 day cycle. In some embodiments, the compound is administered once or twice a day for at least 20, 21, 22, 23 or 24 continuous days followed by a drug holiday until the end of the 28 day cycle. In yet another embodiment, the drug is administered every day without a holiday to achieve continuous dosing during the dosing regimen period, which may be 2, 3, or 4 weeks, or even 1, 2, 3, 4, 5 or 6 or more continual months. In another embodiment, the use of a compound described herein eliminates the need for an off-cycle period, drug holiday, or reduction in co-administered anti-neoplastic compound concentration during treatment. In yet another embodiment, the cycle period is greater than 28 days, such as greater than 30 or 35 days. In certain embodiments, the compound of the present invention is administered for 10, 11, 12,13, 14,15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, or 28 days of a 28-day treatment cycle. In certain embodiments, the compound of the present invention is administered for 14 consecutive days followed by a 14-day dosage holiday. In certain embodiments, the compound of the present invention is administered for 21 consecutive days followed by a 7-day dosage holiday. In certain embodiments, the compound of the present invention is administered once a day for 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, or 28 days of a 28-day treatment cycle. In certain embodiments, the compound of the present invention is administered daily for 14 consecutive days followed by a 14-day dosage holiday. In certain embodiments, the compound of the present invention is administered daily for 21 consecutive days followed by a 7- day dosage holiday. In certain embodiments, the compound of the present invention is administered twice a day for 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, or 28 days of a 28-day treatment cycle. In certain embodiments, the compound of the present invention is administered twice a day for 14 consecutive days followed by a 14-day dosage holiday. In certain embodiments, the compound of the present invention is administered twice a day for 21 consecutive days followed by a 7-day dosage holiday. In certain embodiments, Compound 1 is administered orally daily for 21 days followed by a 7-day holiday within each 28-day treatment cycle. Dosing In certain alternative embodiments the compound of the present invention is administered at a dose of about 800 pg. In certain embodiments, the compound of the present invention is administered at a dose of less than about 600 pg. In certain embodiments, the compound of the present invention is administered at a dose of less than about 400 pg. In certain embodiments, the compound of the present invention is administered at a dose of less than about 300 pg. In certain embodiments, the compound of the present invention is administered at a dose of less than about 200 pg. In certain embodiments, the compound of the present invention is administered at a dose of less than about 100 pg. In certain embodiments, the compound of the present invention is administered at a dose of less than about 50 pg. In certain embodiments, the compound of the present invention is administered at a dose of less than about 25 pg. In certain embodiments, the compound of the present invention is administered at a dose of about 50 ug. In certain embodiments, the compound of the present invention is administered at a dose of about 45 ug. In certain embodiments, the compound of the present invention is administered at a dose of about 40 ug. In certain embodiments, the compound of the present invention is administered at a dose of about 35 ug. In certain embodiments, the compound of the present invention is administered at a dose of about 30 pug. In certain embodiments, the compound of the present invention is administered at a dose of about 25 ug. In certain embodiments, the compound of the present invention is administered at a dose of about 20 ug. In certain embodiments, the compound of the present invention is administered at a dose of about 15 ug. In certain embodiments, the compound of the present invention is administered at a dose of about 10 pug. In certain embodiments, the compound of the present invention is administered at a dose of about 5 ug. In certain embodiments, the compound of the present invention is administered at a dose of about 1 ug. In certain embodiments, Compound 1 is given at a dose of less than about 800 pg. In certain embodiments, Compound 1 is given at a dose of less than about 600 pg. In certain embodiments, Compound 1 is given at a dose of less than about 400 ug. In certain embodiments, Compound 1 is given at a dose of less than about 300 pg. In certain embodiments, Compound 1 is given at a dose of less than about 200 pg. In certain embodiments, Compound 1 is given at a dose of less than about 100 pg. In certain embodiments, Compound 1 is given at a dose of about 800 ng. In certain embodiments, Compound 1 is given at a dose of about 600 pig. In certain embodiments, Compound 1 is given at a dose of about 400 pg. In certain embodiments, Compound 1 is given at a dose of about 300 ug. In certain embodiments, Compound 1 is given at a dose of about 200 pg. In certain embodiments, Compound 1 is given at a dose of about 100 ug. In certain embodiments, Compound 1 is administered at a dose of at least about or between 25, 50, 75, 100, 125, 150, 175, 200, 225, 250, 275, 300, 325, 350, 375, 400, 425, 450, 475, 500, 525, 550, 575, 600, 625, 650, 675, 700, 725, 750, 775, 800, 825, 850, 875, 900, 925, 950, 975, or 1,000 pg. In certain embodiments, Compound 1 is administered at a dose of about 25 ug. In certain embodiments, Compound 1 is administered at a dose of about 50 or 75 ng. In certain embodiments, Compound 1 is administered at a dose of about 100 or 150 ug. In certain embodiments, Compound 1 is administered at a dose of about 175 or 200 ug. In certain embodiments, Compound 1 is administered at a dose of about 225 or 250 pg. In certain embodiments, Compound 1 is administered at a dose of about 275, 300, 325 or 350 pg. In certain embodiments, Compound 1 is administered at a dose of about 400 or 450 pg. In certain embodiments, Compound 1 is administered at a dose of about 550 pig. In certain embodiments, Compound 1 is administered at a dose of about 650 pg. In certain embodiments, Compound 1 is administered at a dose of about 725 pg. In certain embodiments, Compound 1 is administered at a dose of about 800 pg. The present invention includes at least the following low-dose features: (a) a low dose treatment regimen for an Ikaros or Aiolos mediated disorder in a host comprising administering a dose of not more than 500, 450, 400, 350, 300, 250 200, 150 or even 100 micrograms (ug) once a day (QD) or twice a day (BID) to a patient in need thereof of a compound selected from Compound 1, Compound 2, Compound 3, Compound 4, Compound 5, Compound 6, Compound 7, Compound 8, Compound 9, Compound 10, Compound 11, Compound 12, and Compound 13; (b) the treatment of (a) wherein the treatment regimen includes a drug holiday; (c) the treatment of (b) wherein the drug holiday is accomplished with a regimen of therapy once or twice a day for at least 13, 14 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26 or 27 continuous days, and then a holiday taken until the next 28 day cycle; (d) the treatment of (c) wherein therapy is given once or twice a day for 21 days followed by a 7 day holiday; (e) the treatment of (a)-(d) wherein a single dose is not more than 400 micrograms; (f) the treatment of (a)-(d) wherein a single dose is not more than 300, 200 or 100 micrograms; (g) the treatment of (a)-(d) wherein a single dose is not more than 25, 50 or 75 micrograms; (h) the treatment of (b), which may be 2, 3, 4, 5 or 6 weeks, or even 1, 2, 3, 4, 5 or 6 or more months, with dispersed holiday periods; (i) the treatment of (a) that does not include a holiday period; (j) the treatment of (a) wherein the cycle period is greater than 28 days, such as greater than 30 or 35 days, and includes a drug holiday; (k) the treatment of (a)-(j) wherein the disorder selected from diffuse large B-cell lymphoma, anaplastic large cell lymphoma, cutaneous T-cell lymphoma, mantle cell lymphoma, and multiple myeloma, comprising administering an effective amount of Compound 1, Compound 2, Compound 3, Compound 4, Compound 5, Compound 6, Compound 7, Compound 8, Compound 9, Compound 10, Compound 11, Compound 12, or Compound 13 to a patient in need thereof; (1) the treatment of (a)-(j) wherein the disorder that is resistant to treatment with other cereblon ligands, comprising administering an effective amount of Compound 1, Compound 2, Compound 3, Compound 4, Compound 5, Compound 6, Compound 7, Compound 8, Compound 9, Compound 10, Compound 11, Compound 12, or Compound 13 to a patient in need thereof: (m)the treatment of (a)-(j) wherein a patient with a cereblon-mediated disorder comprising monitoring the concentration of one or more biomarkers selected from IRF-1 and caspase- 3: (n) the treatment of (a)-(j) wherein a combination treatment of a patient with a cereblon- mediated disorder comprising administering an effective amount of Compound 1, Compound 2, Compound 3, Compound 4, Compound 5, Compound 6, Compound 7, Compound 8, Compound 9, Compound 10, Compound 11, Compound 12, or Compound 13 to a patient in need thereof in combination or alternation with a Bruton tyrosine kinase inhibitor, corticosteroid, CAR T-cell therapy, antibody-drug conjugate, BiTE therapy, bispecific antibody, or monoclonal antibody; (0) a low does pharmaceutical composition of a compound described herein, or a pharmaceutically acceptable salt, isotopic derivative (including a deuterated derivative), or prodrug thereof in a pharmaceutically acceptable carrier; (p) the treatment according to (a)-(j) of any disorder described herein comprising administering an effective amount of Compound 1, Compound 2, Compound 3, Compound 4, Compound 5, Compound 6, Compound 7, Compound 8, Compound 9, Compound 10, Compound 11, Compound 12, or Compound 13 to a patient in need thereof, (q) a compound described herein, or a pharmaceutically acceptable salt, isotopic derivative, or prodrug thereof, for the treatment according to (a)-(j) of a disorder that is mediated by Ikaros or Aiolos; (r) use of a compound described herein, or a pharmaceutically acceptable salt, isotopic derivative, or prodrug thereof, in an effective amount in the treatment according to (a)-(j) of a patient, typically a human, with any one of the disorders described herein, including those mediated by Ikaros or Aiolos; (s) amethod of manufacturing a low dose medicament for the treatment of a disorder described herein in a host characterized in that a compound described herein is used in the manufacture in the low dosage amounts specified herein; (t) use of a compound described herein, or a pharmaceutically acceptable salt, isotopic derivative, or prodrug thereof in the manufacture of a medicament for the treatment according to (a)-(j) of cancer, including any of the cancers described herein; (u) a method of manufacturing a medicament for the treatment according to (a)-(j)of cancer in a host, including any of the cancers described herein, characterized in that a compound described herein is used in the manufacture; (v) a compound described herein, or a pharmaceutically acceptable salt, isotopic derivative, or prodrug thereof, for the treatment according to (a)-(j) of a tumor in a host, including any of the tumors described herein; (w)use of a compound described herein, or a pharmaceutically acceptable salt, isotopic derivative, or prodrug thereof in the manufacture of a medicament for the treatment according to (a)-(j) of a tumor, including any of the tumors described herein; (x) a method of manufacturing a medicament for the treatment according to (a)-(j) of a tumor in a host, including any of the tumors described herein, characterized in that a compound described herein is used in the manufacture; (y) a compound described herein, or a pharmaceutically acceptable salt, isotopic derivative, or prodrug thereof, for the treatment according to (a)-(j) of an immune, autoimmune, or inflammatory disorder in a host; (z) use of a compound described herein, or a pharmaceutically acceptable salt, isotopic derivative, or prodrug thereof in the manufacture of a medicament for the treatment according to (a)-(j) of an immune, autoimmune, or inflammatory disorder; (aa) a method of manufacturing a medicament for the treatment according to (a)-(j) of an immune, autoimmune, or inflammatory disorder in a host characterized in that a compound described herein is used in the manufacture; (bb) a compound described herein, or a pharmaceutically acceptable salt, isotopic derivative, or prodrug thereof, for the treatment according to (a)-(j) of a hematological malignancy such as multiple myeloma, leukemia, lymphoblastic leukemia, chronic lymphocytic leukemia, Hodgkin's lymphoma, or Non-Hodgkin’s Lymphoma; (cc) use of a compound described herein, or a pharmaceutically acceptable salt, isotopic derivative, or prodrug thereof in the manufacture of a medicament for the treatment according to (a)-(j) of a hematological malignancy such as multiple myeloma, leukemia, lymphoblastic leukemia, chronic lymphocytic leukemia, Hodgkin's lymphoma, or Non- Hodgkin's Lymphoma; (dd) a method of manufacturing a medicament for the treatment according to (a)-(j) of a hematological malignancy in a host such as multiple myeloma, leukemia, lymphoblastic leukemia, chronic lymphocytic leukemia, Hodgkin’s lymphoma, or Non-Hodgkin’s Lymphoma, characterized in that a compound described herein is used in the manufacture; (ee) a pharmaceutical composition comprising an effective host-treating amount according to (a)-(j) of a compound described herein or a pharmaceutically acceptable salt, isotopic derivative, or prodrug thereof with a pharmaceutically acceptable carrier or diluent; (ff) the treatment according to (a)-(j) wherein the compound described herein is a mixture of enantiomers or diastereomers (as relevant), including the racemate; (gg) The treatment according to (a)-(j) wherein a compound described herein in enantiomerically or diastereomerically (as relevant) enriched form, including an isolated enantiomer or diastereomer (i.e. greater than 85, 90, 95, 97, or 99% pure); and (hh) a process for the preparation of therapeutic products that contain a low dose effective amount of a compound described herein. In certain alternative embodiments the compound of the present invention is given at a dose of less than about 800 mg. In certain embodiments, the compound of the present invention is given at a dose of less than about 600 mg. In certain embodiments, the compound of the present invention is given at a dose of less than about 400 mg. In certain embodiments, the compound of the present invention is given at a dose of less than about 300 mg. In certain embodiments, the compound of the present invention is given at a dose of less than about 200 mg. In certain embodiments, the compound of the present invention is given at a dose of less than about 100 mg. In certain embodiments, the compound of the present invention is administered at a dose of about 1,000, 950, 900, 850, 800, 750, 700, 650, 600, 550, 500, 475, 450, 425, 400, 375, 350, 325, 300, 275, 250, 225, 200, 175, 150, 125, 100, 90, 80, 75, 70, 65, 60, 55, 50, 45, 40, 35, 30, 25, 20, 15, 10, 5, or 1 mg. In certain embodiments, the compound of the present invention is administered at a dose of about 1,000, 950, 900, 850, 800, 750, 700, 650, 600, 550, 500, 475, 450, 425, 400, 375, 350, 325, 300, 275, 250, 225, 200, 175, 150, 125, 100, 90, 80, 75, 70, 65, 60, 55, 50, 45, 40, 35, 30, 25, 20, 15,10, 5,0r1 pg. In certain embodiments, the compound of the present invention is administered at a dose of at least about 1,000, 950, 900, 850, 800, 750, 700, 650, 600, 550, 500, 475, 450, 425, 400, 375, 350, 325, 300, 275, 250, 225, 200, 175, 150, 125, 100, 90, 80, 75, 70, 65, 60, 55, 50, 45, 40, 35, 30, 25, 20, 15, 10, 5, or 1 pg. In certain embodiments, the compound of the present invention is administered at a dose of less than least about 1,000, 950, 900, 850, 800, 750, 700, 650, 600, 550, 500, 475, 450, 425, 400, 375, 350, 325, 300, 275, 250, 225, 200, 175, 150, 125, 100, 90, 80, 75, 70, 65, 60, 55, 50, 45, 40, 35, 30, 25, 20, 15, 10, 5, or 1 pg. Disorders Mediated by Ikaros and / or Aiolos In one aspect of the present invention a disorder mediated by Ikaros or Aiolos is treated by Compound 1, or a pharmaceutically acceptable salt thereof, or another compound described herein. In certain embodiments, the cancer is a hematopoietic cancer. In some embodiments, the cancer is a lymphoma, leukemia or myeloma. In certain aspects, the cancer is a Non-Hodgkin's Lymphoma or a Hodgkin’s lymphoma. In certain embodiments, the compound of the present invention is administered to a patient in need thereof in an effective amount to treat diffuse large B-cell lymphoma. In certain embodiments, the diffuse large B-cell lymphoma is an activated B-cell lymphoma or a germinal center B-cell lymphoma. In certain embodiments, the diffuse large B-cell lymphoma is a BCL2 / 6 translocation bearing cancer. In certain embodiments, the diffuse large B-cell lymphoma is a double hit bearing cancer. In certain embodiments, the diffuse large B-cell lymphoma is a BCL2 / 6 MYC wild type cancer. In certain embodiments the compound of the present invention increases the concentration of Caspase-3 and / or Caspase-7. In certain embodiments this increased concentration of Caspase-3 and / or caspase-7 drives cancer cell death, for example mediating the treatment of diffuse large B- cell lymphoma. In certain embodiments, the compound of the present invention is administered to a patient in need thereof in an effective amount to treat anaplastic large cell lymphoma. In certain embodiments, the compound of the present invention is administered to a patient in need thereof in an effective amount to treat cutaneous T-cell lymphoma. In certain embodiments, the compound of the present invention is administered to a patient in need thereof in an effective amount to treat mantle cell lymphoma. In certain embodiments, the compound of the present invention is administered to a patient in need thereof in an effective amount to treat multiple myeloma. In certain embodiments, the compound of the present invention is administered to a patient in need thereof in an effective amount to treat a disorder that is resistant to treatment with other cereblon ligands. In certain embodiments, the compound of the present invention is used to treat an IMiD-refractory disorder. In certain embodiments, Compound 1 is administered to a patient in need thereof in an effective amount to treat diffuse large B-cell lymphoma. In certain embodiments, the diffuse large B-cell lymphoma is an activated B-cell lymphoma or a germinal center B-cell lymphoma. In certain embodiments, the diffuse large B-cell lymphoma is a BCL2 / 6 translocation bearing cancer. In certain embodiments, the diffuse large B-cell lymphoma is a double hit bearing cancer. In certain embodiments, the diffuse large B-cell lymphoma is a BCL2 / 6 MYC wild type cancer. In certain embodiments, Compound 1 is administered to a patient in need thereof in an effective amount to treat anaplastic large cell lymphoma. In certain embodiments, Compound 1 is administered to a patient in need thereof in an effective amount to treat cutaneous T-cell lymphoma. In certain embodiments, Compound 1 is administered to a patient in need thereof in an effective amount to treat mantle cell lymphoma. In certain embodiments, Compound 1 is administered to a patient in need thereof in an effective amount to treat multiple myeloma. In certain embodiments, Compound 1 is administered to a patient in need thereof in an effective amount to treat a disorder that is resistant to treatment with other cereblon ligands. In certain embodiments, Compound 1 is administered to a patient in need thereof in an effective amount to treat an IMiD-refractory disorder. In one aspect an effective amount of a compound described herein, or a pharmaceutically acceptable salt thereof, is administered to a patient to treat a CNS involved cancer, for example a lymphoma in the CNS. In certain embodiments, the patient with a CNS involved cancer, for example a lymphoma in the CNS, is also administered one or more additional therapeutic agents, for example ibrutinib or rituximab. In certain embodiments, a compound described herein is used in the treatment of a peripheral central nervous system lymphoma. In certain embodiments, Compound 1 is administered for the treatment of PTCL-NOS (i.e. PTCL that is not otherwise specified). In other embodiments Compound 1 is administered for the treatment of PTCL with a specified subtype for example anaplastic large cell lymphoma (ALCL), angioimmunoblastic T-Cell lymphoma (AITL), enteropathy-type T-cell lymphoma, extranodal natural killer (NK) cell lymphoma, or extranodal T-cell lymphoma. In certain embodiments, the disorder treated by a compound of the present invention is an immunomodulatory disorder. In certain embodiments, the disorder treated by a compound of the present invention is mediated by angiogenesis. In certain embodiments, the disorder treated by a compound of the present invention is related to the lymphatic system. In certain embodiments, a compound of the present invention or pharmaceutical salt thereof, optionally in a pharmaceutical composition as described herein is administered to a patient in need thereof in an effective amount to degrade Ikaros or Aiolos, which is a mediator of the disorder affecting the patient, such as a human. The control of protein level afforded by any of the compounds of the present invention provides treatment of a disease state or condition, which is modulated through Ikaros or Aiolos by lowering the level of that protein in the cell, e.g., cell of a patient, or by lowering the level of downstream proteins in the cell. In certain embodiments, the treatment comprises administering an effective amount of the compound as described herein, optionally including a pharmaceutically acceptable excipient, carrier, adjuvant (i.e, a pharmaceutically acceptable composition), optionally in combination or alternation with another bioactive agent or combination of agents. In certain embodiments, a compound of the present invention is administered to a patient in need thereof in an effective amount to treat a disorder including, but not limited to, benign growth, neoplasm, tumor, cancer, abnormal cellular proliferation, immune disorder, inflammatory disorder, graft-versus-host rejection, viral infection, bacterial infection, an amyloid-based proteinopathy, a proteinopathy, or a fibrotic disorder. The term “disease state” or “condition” when used in connection with any of the compounds is meant to refer to any disease state or condition that is mediated by Ikaros or Aiolos, such as cellular proliferation, or by proteins that are downstream of Ikaros or Aiolos, and where degradation of such protein in a patient may provide beneficial therapy or relief of symptoms to a patient in need thereof. In certain instances, the disease state or condition may be cured. In certain embodiments, a compound or its corresponding pharmaceutically acceptable salt, isotopic derivative, or prodrug as described herein can be administered in an effective amount to treat a host, for example a human, with a lymphoma or lymphocytic or myelocytic proliferation disorder or abnormality. For example, a compound as described herein can be administered to a host suffering from a Hodgkin Lymphoma or a Non-Hodgkin Lymphoma. For example, the host can be suffering from a Non-Hodgkin Lymphoma such as, but not limited to: an AIDS-Related Lymphoma; Anaplastic Large-Cell Lymphoma; Angioimmunoblastic Lymphoma; Blastic NK- Cell Lymphoma; Burkitt’s Lymphoma; Burkitt-like Lymphoma (Small Non-Cleaved Cell Lymphoma); diffuse small-cleaved cell lymphoma (DSCCL), Chronic Lymphocytic Leukemia, Small Lymphocytic Lymphoma; Non-Hodgkin lymphoma NOS, Cutaneous T-Cell Lymphoma; Diffuse Large B-Cell Lymphoma; Enteropathy-Type T-Cell Lymphoma; Follicular Lymphoma; Hepatosplenic Gamma-Delta T-Cell Lymphoma; Lymphoblastic Lymphoma; Mantle Cell Lymphoma; Marginal Zone Lymphoma, Nasal T-Cell Lymphoma; Pediatric Lymphoma; Peripheral Lymphoma, Peripheral T-Cell Lymphomas; Primary Central Nervous System Lymphoma; T-Cell Leukemias, Transformed Lymphomas; Treatment-Related T-Cell Lymphomas; Langerhans cell histiocytosis; or Waldenstrom's Macroglobulinemia. In another embodiment, a compound or its corresponding pharmaceutically acceptable salt, isotopic derivative, or prodrug as described herein can be administered in an effective amount to treat a host, for example a human, with a Hodgkin lymphoma, such as, but not limited to: Nodular Sclerosis Classical Hodgkin’s Lymphoma (CHL); Mixed Cellularity CHL; Lymphocyte-depletion CHL; Lymphocyte-rich CHL; Lymphocyte Predominant Hodgkin Lymphoma; or Nodular Lymphocyte Predominant HL. In another embodiment, a compound or its corresponding pharmaceutically acceptable salt, isotopic derivative, or prodrug as described herein can be administered in an effective amount to treat a host, for example a human, with an immunomodulatory condition. Non-limiting examples of immunomodulatory conditions include: arthritis, lupus, celiac disease, Sjogren’s syndrome, polymyalgia rheumatia, multiple sclerosis, ankylosing spondylitis, type 1 diabetes, alopecia areata, vasculitis, and temporal arteritis. In certain embodiments, the condition treated with a compound of the present invention is a disorder related to abnormal cellular proliferation. Abnormal cellular proliferation, notably hyperproliferation, can occur as a result of a wide variety of factors, including genetic mutation, infection, exposure to toxins, autoimmune disorders, and benign or malignant tumor induction. Abnormal proliferation of B-cells, T-cells, and / or NK cells can result in a wide range of diseases such as cancer, proliferative disorders and inflammatory / immune diseases. A host, for example a human, afflicted with any of these disorders can be treated with an effective amount of a compound as described herein to achieve a decrease in symptoms (palliative agent) or a decrease in the underlying disease (a disease modifying agent). In certain embodiments, a compound or its corresponding pharmaceutically acceptable salt, isotopic derivative, or prodrug as described herein can be administered in an effective amount to treat a host, for example a human, with a specific B-cell lymphoma or proliferative disorder such as, but not limited to: multiple myeloma; Diffuse large B cell lymphoma; Follicular lymphoma; Mucosa-Associated Lymphatic Tissue lymphoma (MALT); Small cell lymphocytic lymphoma, diffuse poorly differentiated lymphocytic lymphoma; Mediastinal large B cell lymphoma; Nodal marginal zone B cell lymphoma (NMZL), Splenic marginal zone lymphoma (SMZL), Intravascular large B-cell lymphoma, Primary effusion lymphoma; or Lymphomatoid granulomatosis; B-cell prolymphocytic leukemia, Hairy cell leukemia; Splenic lymphoma / leukemia, unclassifiable; Splenic diffuse red pulp small B-cell lymphoma; Hairy cell leukemia-variant; Lymphoplasmacytic lymphoma; Heavy chain diseases, for example, Alpha heavy chain disease, Gamma heavy chain disease, Mu heavy chain disease; Plasma cell myeloma; Solitary plasmacytoma of bone; Extraosseous plasmacytoma; Primary cutaneous follicle center lymphoma; T cell / histiocyte rich large B-cell lymphoma; DLBCL associated with chronic inflammation; Epstein-Barr virus (EBV)+ DLBCL of the elderly; Primary mediastinal (thymic) large B-cell lymphoma; Primary cutaneous DLBCL, leg type; ALK+ large B-cell lymphoma; Plasmablastic lymphoma; Large B-cell lymphoma arising in HHV8-associated multicentric; Castleman disease; B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma; or B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma and classical Hodgkin lymphoma. In certain embodiments, a compound or its corresponding pharmaceutically salt, isotopic derivative, or prodrug as described herein can be administered in an effective amount to treat a host, for example a human, with a T-cell or NK-cell lymphoma such as, but not limited to: anaplastic lymphoma kinase (ALK) positive, ALK negative anaplastic large cell lymphoma, or primary cutaneous anaplastic large cell lymphoma; angicimmunoblastic lymphoma; cutaneous T- cell lymphoma, for example mycosis fungoides, Sézary syndrome, primary cutaneous anaplastic large cell lymphoma, primary cutaneous CD30+ T-cell lymphoproliferative disorder; primary cutaneous aggressive epidermotropic CD8+ cytotoxic T-cell lymphoma; primary cutaneous gamma-delta T-cell lymphoma; primary cutaneous small / medium CD4+ T-cell lymphoma, and lymphomatoid papulosis; Adult T-cell Leukemia / Lymphoma (ATLL); Blastic NK-cell Lymphoma; Enteropathy-type T-cell lymphoma; Hematosplenic gamma-delta T-cell Lymphoma; Lymphoblastic Lymphoma; Nasal NK / T-cell Lymphomas; Treatment-related T-cell lymphomas; for example lymphomas that appear after solid organ or bone marrow transplantation; T-cell prolymphocytic leukemia, T-cell large granular lymphocytic leukemia; Chronic lymphoproliferative disorder of NK-cells; Aggressive NK cell leukemia; Systemic EBV+ T-cell lymphoproliferative disease of childhood (associated with chronic active EBV infection); Hydroa vacciniforme-like lymphoma; Adult T-cell leukemia / lymphoma; Enteropathy-associated T-cell lymphoma; Hepatosplenic T-cell lymphoma; or Subcutaneous panniculitis-like T-cell lymphoma. In certain embodiments, a compound or its corresponding pharmaceutically acceptable salt, isotopic derivative, or prodrug as described herein can be administered to treat a host, for example a human, with leukemia. For example, the host may be suffering from an acute or chronic leukemia of a lymphocytic or myelogenous origin, such as, but not limited to: Acute lymphoblastic leukemia (ALL), Acute myelogenous leukemia (AML); Chronic lymphocytic leukemia (CLL); Chronic myelogenous leukemia (CML); juvenile myelomonocytic leukemia (JMML); hairy cell leukemia (HCL); acute promyelocytic leukemia (a subtype of AML); large granular lymphocytic leukemia; or Adult T-cell chronic leukemia. In certain embodiments, the patient suffers from an acute myelogenous leukemia, for example an undifferentiated AML (MO); myeloblastic leukemia (M1; with / without minimal cell maturation); myeloblastic leukemia (M2; with cell maturation); promyelocytic leukemia (M3 or M3 variant [M3 V]); myelomonocytic leukemia (M4 or M4 variant with eosinophilia [M4E]); monocytic leukemia (M5); erythroleukemia (M6); or megakaryoblastic leukemia (M7). There are a number of skin disorders associated with cellular hyperproliferation. Psoriasis, for example, is a benign disease of human skin generally characterized by plaques covered by thickened scales. The disease is caused by increased proliferation of epidermal cells of unknown cause. Chronic eczema is also associated with significant hyperproliferation of the epidermis. Other diseases caused by hyperproliferation of skin cells include atopic dermatitis, lichen planus, warts, pemphigus vulgaris, actinic keratosis, basal cell carcinoma and squamous cell carcinoma. Other hyperproliferative cell disorders include blood vessel proliferation disorders, fibrotic disorders, autoimmune disorders, graft-versus-host rejection, tumors and cancers. Blood vessel proliferative disorders include angiogenic and vasculogenic disorders. Proliferation of smooth muscle cells in the course of development of plaques in vascular tissue cause, for example, restenosis, retinopathies and atherosclerosis. Both cell migration and cell proliferation play a role in the formation of atherosclerotic lesions. Fibrotic disorders are often due to the abnormal formation of an extracellular matrix. Examples of fibrotic disorders include hepatic cirrhosis and mesangial proliferative cell disorders. Hepatic cirrhosis is characterized by the increase in extracellular matrix constituents resulting in the formation of a hepatic scar. Hepatic cirrhosis can cause diseases such as cirrhosis of the liver. An increased extracellular matrix resulting in a hepatic scar can also be caused by viral infection such as hepatitis. Lipocytes appear to play a major role in hepatic cirrhosis. Mesangial disorders are brought about by abnormal proliferation of mesangial cells. Mesangial hyperproliferative cell disorders include various human renal diseases, such as glomerulonephritis, diabetic nephropathy, malignant nephrosclerosis, thrombotic micro- angiopathy syndromes, transplant rejection, and glomerulopathies. Another disease with a proliferative component is rheumatoid arthritis. Rheumatoid arthritis is generally considered an autoimmune disease that is thought to be associated with activity of autoreactive T cells, and to be caused by autoantibodies produced against collagen and IgE. Other disorders that can include an abnormal cellular proliferative component include Bechet’s syndrome, acute respiratory distress syndrome (ARDS), ischemic heart disease, post- dialysis syndrome, leukemia, acquired immune deficiency syndrome, vasculitis, lipid histiocytosis, septic shock and inflammation in general. A compound or its pharmaceutically acceptable salt, isotopic analog, or prodrug as described herein can be administered in an effective amount to treat a host, for example a human, with a proliferative condition such as myeloproliferative disorder (MPD), polycythemia vera (PV), essential thrombocythemia (ET), myeloid metaplasia with myelofibrosis (MMM), chronic myelomonocytic leukemia (CMML), hypereosinophilic syndrome (HES), system mast cell disease (SMCD), and the like. In another embodiment, a compound provided herein is useful for the treatment of primary myelofibrosis, post-polycythemia vera myelofibrosis, post-essential thrombocythemia myelofibrosis, and secondary acute myelogenous leukemia. In certain embodiments, a compound or its pharmaceutically acceptable salt, isotopic analog, or prodrug as described herein can be administered in an effective amount to treat a host, for example a human, with a myelodysplastic syndrome (MDS) such as, but not limited to: refractory cytopenia with unilineage dysplasia, refractory anemia with ring sideroblasts (RARS), refractory anemia with ring sideroblasts — thrombocytosis (RARS-t), refractory cytopenia with multilineage dysplasia (RCMD) including RCMD with multilineage dysplasia and ring sideroblasts (RCMD-RS), Refractory amenias with excess blasts I (RAEB-I) and II (RAEB-II), 5q- syndrome, refractory cytopenia of childhood, and the like. In certain embodiments, a compound of the present invention can provide a therapeutic effect by direct degradation of Ikaros or Aiolos which may change the transcriptional regulation of a protein downstream of Ikaros or Aiolos. The term “neoplasia” or “cancer” is used to refer to the pathological process that results in the formation and growth of a cancerous or malignant neoplasm, i.e., abnormal tissue that grows by cellular proliferation, often more rapidly than normal and continues to grow after the stimuli that initiated the new growth cease. Malignant neoplasms show partial or complete lack of structural organization and functional coordination with the normal tissue and most invade surrounding tissues, metastasize to several sites, and are likely to recur after attempted removal and to cause the death of the patient unless adequately treated. As used herein, the term neoplasia is used to describe all cancerous disease states and embraces or encompasses the pathological process associated with malignant hematogenous, ascitic and solid tumors. Exemplary cancers which may be treated by the present compounds either alone or in combination with at least one additional anti-cancer agent include squamous-cell carcinoma, basal cell carcinoma, adenocarcinoma, hepatocellular carcinomas, and renal cell carcinomas, cancer of the bladder, bowel, breast, cervix, colon, esophagus, head, kidney, liver, lung, neck, ovary, pancreas, prostate, and stomach; leukemias; benign and malignant lymphomas, particularly Burkitt's lymphoma and Non-Hodgkin's Lymphoma; benign and malignant melanomas; myeloproliferative diseases; sarcomas, including Ewing's sarcoma, hemangiosarcoma, Kaposi's sarcoma, liposarcoma, myosarcomas, peripheral neuroepithelioma, synovial sarcoma, gliomas, astrocytomas, oligodendrogliomas, ependymomas, gliobastomas, neuroblastomas, ganglioneuromas, gangliogliomas, medulloblastomas, pineal cell tumors, meningiomas, meningeal sarcomas, neurofibromas, and Schwannomas; bowel cancer, breast cancer, prostate cancer, cervical cancer, uterine cancer, lung cancer, ovarian cancer, testicular cancer, thyroid cancer, astrocytoma, esophageal cancer, pancreatic cancer, stomach cancer, liver cancer, colon cancer, melanoma; carcinosarcoma, Hodgkin's disease, Wilms' tumor and teratocarcinomas. Additional cancers which may be treated using compounds according to the present invention include, for example, T- lineage Acute lymphoblastic Leukemia (T-ALL), T-lineage lymphoblastic Lymphoma (T-LL), Peripheral T-cell lymphoma, Adult T-cell Leukemia, Pre-B ALL, Pre-B Lymphomas, Large B- cell Lymphoma, Burkitts Lymphoma, B-cell ALL, Philadelphia chromosome positive ALL and Philadelphia chromosome positive CML. Additional cancers which may be treated using the disclosed compounds according to the present invention include, for example, acute granulocytic leukemia, acute lymphocytic leukemia (ALL), acute myelogenous leukemia (AML), adenocarcinoma, adenosarcoma, adrenal cancer, adrenocortical carcinoma, anal cancer, anaplastic astrocytoma, angiosarcoma, appendix cancer, astrocytoma, Basal cell carcinoma, B-Cell lymphoma, bile duct cancer, bladder cancer, bone cancer, bone marrow cancer, bowel cancer, brain cancer, brain stem glioma, breast cancer, triple (estrogen, progesterone and HER-2) negative breast cancer, double negative breast cancer (two of estrogen, progesterone and HER-2 are negative), single negative (one of estrogen, progesterone and HER-2 is negative), estrogen-receptor positive, HER2-negative breast cancer, estrogen receptor-negative breast cancer, estrogen receptor positive breast cancer, metastatic breast cancer, luminal A breast cancer, luminal B breast cancer, Her2-negative breast cancer, HER2-positive or negative breast cancer, progesterone receptor-negative breast cancer, progesterone receptor- positive breast cancer, recurrent breast cancer, carcinoid tumors, cervical cancer, cholangiocarcinoma, chondrosarcoma, chronic lymphocytic leukemia (CLL), chronic myelogenous leukemia (CML), colon cancer, colorectal cancer, craniopharyngioma, cutaneous lymphoma, cutaneous melanoma, diffuse astrocytoma, ductal carcinoma in situ (DCIS), endometrial cancer, ependymoma, epithelioid sarcoma, esophageal cancer, ewing sarcoma, extrahepatic bile duct cancer, eye cancer, fallopian tube cancer, fibrosarcoma, gallbladder cancer, gastric cancer, gastrointestinal cancer, gastrointestinal carcinoid cancer, gastrointestinal stromal tumors (GIST), germ cell tumor glioblastoma multiforme (GBM), glioma, hairy cell leukemia, head and neck cancer, hemangioendothelioma, Hodgkin lymphoma, hypopharyngeal cancer, infiltrating ductal carcinoma (IDC), infiltrating lobular carcinoma (ILC), inflammatory breast cancer (IBC), intestinal Cancer, intrahepatic bile duct cancer, invasive / infiltrating breast cancer, Islet cell cancer, jaw cancer, Kaposi sarcoma, kidney cancer, laryngeal cancer, leiomyosarcoma, leptomeningeal metastases, leukemia, lip cancer, liposarcoma, liver cancer, lobular carcinoma in situ, low-grade astrocytoma, lung cancer, lymph node cancer, lymphoma, male breast cancer, medullary carcinoma, medulloblastoma, melanoma, meningioma, Merkel cell carcinoma, mesenchymal chondrosarcoma, mesenchymous, mesothelioma metastatic breast cancer, metastatic melanoma metastatic squamous neck cancer, mixed gliomas, monodermal teratoma, mouth cancer mucinous carcinoma, mucosal melanoma, multiple myeloma, Mycosis Fungoides, myelodysplastic syndrome, nasal cavity cancer, nasopharyngeal cancer, neck cancer, neuroblastoma, neuroendocrine tumors (NETs), Non-Hodgkin's Lymphoma, non-small cell lung cancer (NSCLC), oat cell cancer, ocular cancer, ocular melanoma, oligodendroglioma, oral cancer, oral cavity cancer, oropharyngeal cancer, osteogenic sarcoma, osteosarcoma, ovarian cancer, ovarian epithelial cancer ovarian germ cell tumor, ovarian primary peritoneal carcinoma, ovarian sex cord stromal tumor, Paget's disease, pancreatic cancer, papillary carcinoma, paranasal sinus cancer, parathyroid cancer, pelvic cancer, penile cancer, peripheral nerve cancer, peritoneal cancer, pharyngeal cancer, pheochromocytoma, pilocytic astrocytoma, pineal region tumor, pineoblastoma, pituitary gland cancer, primary central nervous system (CNS) lymphoma, prostate cancer, rectal cancer, renal cell carcinoma, renal pelvis cancer, rhabdomyosarcoma, salivary gland cancer, soft tissue sarcoma, bone sarcoma, sarcoma, sinus cancer, skin cancer, small cell lung cancer (SCLC), small intestine cancer, spinal cancer, spinal column cancer, spinal cord cancer, squamous cell carcinoma, stomach cancer, synovial sarcoma, T-cell lymphoma, testicular cancer, throat cancer, thymoma / thymic carcinoma, thyroid cancer, tongue cancer, tonsil cancer, transitional cell cancer, tubal cancer, tubular carcinoma, undiagnosed cancer, ureteral cancer, urethral cancer, uterine adenocarcinoma, uterine cancer, uterine sarcoma, vaginal cancer, vulvar cancer, T-cell lineage acute lymphoblastic leukemia (T-ALL), T-cell lineage lymphoblastic lymphoma (T-LL), peripheral T-cell lymphoma, Adult T-cell leukemia, Pre-B ALL, Pre-B lymphomas, large B-cell lymphoma, Burkitts lymphoma, B-cell ALL, Philadelphia chromosome positive ALL, Philadelphia chromosome positive CML, juvenile myelomonocytic leukemia (JMML), acute promyelocytic leukemia (a subtype of AML), large granular lymphocytic leukemia, Adult T-cell chronic leukemia, diffuse large B cell lymphoma, follicular lymphoma; Mucosa-Associated Lymphatic Tissue lymphoma (MALT), small cell lymphocytic lymphoma, mediastinal large B cell lymphoma, nodal marginal zone B cell lymphoma (NMZL), splenic marginal zone lymphoma (SMZL), intravascular large B-cell lymphoma; primary effusion lymphoma; or lymphomatoid granulomatosis; B-cell prolymphocytic leukemia; splenic lymphoma / leukemia, unclassifiable, splenic diffuse red pulp small B-cell lymphoma; lymphoplasmacytic lymphoma; heavy chain diseases, for example, Alpha heavy chain disease, Gamma heavy chain disease, Mu heavy chain disease, plasma cell myeloma, solitary plasmacytoma of bone; extraosseous plasmacytoma; primary cutaneous follicle center lymphoma, T cell / histocyte rich large B-cell lymphoma, DLBCL associated with chronic inflammation; Epstein-Barr virus (EBV)+ DLBCL of the elderly; primary mediastinal (thymic) large B-cell lymphoma, primary cutaneous DLBCL, leg type, ALK+ large B-cell lymphoma, plasmablastic lymphoma; large B-cell lymphoma arising in HHV8-associated multicentric, Castleman disease; B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma, or B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma and classical Hodgkin lymphoma. In certain embodiments, the disorder is adenoid cystic carcinoma. In certain embodiments, the disorder is NUT midline carcinoma. In another embodiment, a compound or its pharmaceutically acceptable salt, isotopic derivative or prodrug as described herein can be used in an effective amount to treat a host, for example a human, with an autoimmune disorder, Examples include, but are not limited to: Acute disseminated encephalomyelitis (ADEM); Addison's disease; Agammaglobulinemia; Alopecia areata, Amyotrophic lateral sclerosis (Also Lou Gehrig's disease; Motor Neuron Disease); Ankylosing Spondylitis; Antiphospholipid syndrome; Antisynthetase syndrome; Atopic allergy; Atopic dermatitis; Autoimmune aplastic anemia; Autoimmune arthritis; Autoimmune cardiomyopathy; Autoimmune enteropathy; Autoimmune granulocytopenia; Autoimmune hemolytic anemia; Autoimmune hepatitis; Autoimmune hypoparathyroidism; Autoimmune inner ear disease; Autoimmune lymphoproliferative syndrome; Autoimmune myocarditis; Autoimmune pancreatitis; Autoimmune peripheral neuropathy; Autoimmune ovarian failure; Autoimmune polyendocrine syndrome; Autoimmune progesterone dermatitis; Autoimmune thrombocytopenic purpura; Autoimmune thyroid disorders; Autoimmune urticarial, Autoimmune uveitis; Autoimmune vasculitis; Balo disease / Balo concentric sclerosis; Behget's disease; Berger's disease; Bickerstaff's encephalitis, Blau syndrome; Bullous pemphigoid; Cancer; Castleman's disease; Celiac disease; Chagas disease; Chronic inflammatory demyelinating polyneuropathy; Chronic inflammatory demyelinating polyneuropathy; Chronic obstructive pulmonary disease; Chronic recurrent multifocal osteomyelitis; Churg-Strauss syndrome; Cicatricial pemphigoid, Cogan syndrome; Cold agglutinin disease; Complement component 2 deficiency; Contact dermatitis; Cranial arteritis; CREST syndrome; Crohn's disease; Cushing's Syndrome; Cutaneous leukocytoclastic angiitis; Dego's disease; Dercum's disease; Dermatitis herpetiformis; Dermatomyositis; Diabetes mellitus type 1; Diffuse cutaneous systemic sclerosis; Discoid lupus erythematosus; Dressler's syndrome; Drug-induced lupus; Eczema; Endometriosis; Enthesitis- related arthritis; Eosinophilic fasciitis; Eosinophilic gastroenteritis; Eosinophilic pneumonia; Epidermolysis bullosa acquisita; Erythema nodosum; Erythroblastosis fetalis; Essential mixed cryoglobulinemia; Evan's syndrome; Extrinsic and intrinsic reactive airways disease (asthma); Fibrodysplasia ossificans progressive; Fibrosing alveolitis (or Idiopathic pulmonary fibrosis); Gastritis; Gastrointestinal pemphigoid, Glomerulonephritis; Goodpasture's syndrome; Graves' disease; Guillain-Barré syndrome (GBS); Hashimoto's encephalopathy; Hashimoto's thyroiditis; Hemolytic anemia; Henoch-Schonlein purpura; Herpes gestationis (Gestational Pemphigoid); Hidradenitis suppurativa; Hughes-Stovin syndrome; Hypogammaglobulinemia, Idiopathic inflammatory ~~ demyelinating diseases; Idiopathic pulmonary fibrosis; Idiopathic thrombocytopenic purpura; IgA nephropathy; Immune glomerulonephritis; Immune nephritis; Immune pneumonitis; Inclusion body myositis; inflammatory bowel disease; Interstitial cystitis; Juvenile idiopathic arthritis aka Juvenile rheumatoid arthritis; Kawasaki's disease; Lambert-Eaton myasthenic syndrome; Leukocytoclastic vasculitis; Lichen planus; Lichen sclerosus; Linear IgA disease (LAD); Lupoid hepatitis aka Autoimmune hepatitis; Lupus erythematosus; Majeed syndrome; microscopic polyangiitis; Miller-Fisher syndrome; mixed connective tissue disease; Morphea; Mucha-Habermann disease aka Pityriasis lichenoides et varioliformis acuta; Multiple sclerosis; Myasthenia gravis; Myositis; Méniére's disease; Narcolepsy, Neuromyelitis optica (also Devic's disease); Neuromyotonia; Occular cicatricial pemphigoid; Opsoclonus myoclonus syndrome; Ord's thyroiditis; Palindromic rheumatism; PANDAS (pediatric autoimmune neuropsychiatric disorders associated with streptococcus); Paraneoplastic cerebellar degeneration; Paroxysmal nocturnal hemoglobinuria (PNH); Parry Romberg syndrome; Pars planitis; Parsonage- Tumer syndrome; Pemphigus vulgaris; Perivenous encephalomyelitis; Pernicious anaemia; POEMS syndrome; Polyarteritis nodosa; Polymyalgia rheumatic, Polymyositis; Primary biliary cirrhosis; Primary sclerosing cholangitis; Progressive inflammatory neuropathy; Psoriasis; Psoriatic arthritis, pure red cell aplasia; Pyoderma gangrenosum; Rasmussen's encephalitis; Raynaud phenomenon; Reiter's syndrome; relapsing polychondritis, restless leg syndrome; retroperitoneal fibrosis; rheumatic fever, rheumatoid arthritis; Sarcoidosis; Schizophrenia; Schmidt syndrome; Schnitzler syndrome; Scleritis; Scleroderma; Sclerosing cholangitis; serum sickness; Sjogren's syndrome; Spondyloarthropathy; Stiff person syndrome; Still's disease; Subacute bacterial endocarditis (SBE); Susac's syndrome; Sweet's syndrome; Sydenham chorea; sympathetic ophthalmia; systemic lupus erythematosus; Takayasu's arteritis; temporal arteritis (also known as "giant cell arteritis"); thrombocytopenia, Tolosa-Hunt syndrome; transverse myelitis; ulcerative colitis; undifferentiated connective tissue disease; undifferentiated spondyloarthropathy; urticarial vasculitis; vasculitis; vitiligo; viral diseases such as Epstein Barr Virus (EBV), Hepatitis B, Hepatitis C, HIV, HTLV 1, Varicella-Zoster Virus (VZV) and Human Papilloma Virus (HPV); or Wegener's granulomatosis. In some embodiments, the autoimmune disease is an allergic condition, including those from asthma, food allergies, atopic dermatitis, chronic pain, and rhinitis. Cutaneous contact hypersensitivity and asthma are just two examples of immune responses that can be associated with significant morbidity. Others include atopic dermatitis, eczema, Sjogren's Syndrome, including keratoconjunctivitis sicca secondary to Sjogren's Syndrome, alopecia areata, allergic responses due to arthropod bite reactions, Crohn's disease, aphthous ulcer, iritis, conjunctivitis, keratoconjunctivitis, ulcerative colitis, cutaneous lupus erythematosus, scleroderma, vaginitis, proctitis, and drug eruptions. These conditions may result in any one or more of the following symptoms or signs: itching, swelling, redness, blisters, crusting, ulceration, pain, scaling, cracking, hair loss, scarring, or oozing of fluid involving the skin, eye, or mucosal membranes. In atopic dermatitis, and eczema in general, immunologically mediated leukocyte infiltration (particularly infiltration of mononuclear cells, lymphocytes, neutrophils, and eosinophils) into the skin importantly contributes to the pathogenesis of these diseases. Chronic eczema also is associated with significant hyperproliferation of the epidermis. Immunologically mediated leukocyte infiltration also occurs at sites other than the skin, such as in the airways in asthma and in the tear producing gland of the eye in keratoconjunctivitis sicca. A compound or its pharmaceutically acceptable salt, isotopic variant, or prodrug as described herein can be administered in an effective amount to treat a host, for example a human, with a skin disorder such as psoriasis (for example, psoriasis vulgaris), atopic dermatitis, skin rash, skin irritation, skin sensitization (e.g., contact dermatitis or allergic contact dermatitis). For example, certain substances including some pharmaceuticals when topically applied can cause skin sensitization. In some embodiments, the skin disorder is treated by topical administration of compounds known in the art in combination with the compounds disclosed herein. In one non- limiting embodiment compounds of the present invention are used as topical agents in treating contact dermatitis, atopic dermatitis, eczematous dermatitis, psoriasis, Sjogren's Syndrome, including keratoconjunctivitis sicca secondary to Sjogren's Syndrome, alopecia areata, allergic responses due to arthropod bite reactions, Crohn's disease, aphthous ulcer, iritis, conjunctivitis, keratoconjunctivitis, ulcerative colitis, asthma, allergic asthma, cutaneous lupus erythematosus, scleroderma, vaginitis, proctitis, and drug eruptions. Disease states of conditions which may be treated using compounds according to the present invention include, for example, asthma, autoimmune diseases such as multiple sclerosis, various cancers, ciliopathies, cleft palate, diabetes, heart disease, hypertension, inflammatory bowel disease, mental retardation, mood disorder, obesity, refractive error, infertility, Angelman syndrome, Canavan disease, Coeliac disease, Charcot-Marie-Tooth disease, Cystic fibrosis, Duchenne muscular dystrophy, Haemochromatosis, Haemophilia, Klinefelter's syndrome, Neurofibromatosis, Phenylketonuria, Polycystic kidney disease 1 (PKD1) or 2 (PKD2) Prader- ‘Willi syndrome, Sickle-cell disease, Tay-Sachs disease, Turner syndrome. Further disease states or conditions which may be treated by compounds according to the present invention include Alzheimer's disease, Amyotrophic lateral sclerosis (Lou Gehrig's disease), Anorexia nervosa, Anxiety disorder, Atherosclerosis, Attention deficit hyperactivity disorder, Autism, Bipolar disorder, Chronic fatigue syndrome, Chronic obstructive pulmonary disease, Crohn's disease, Coronary heart disease, Dementia, Depression, Diabetes mellitus type 1, Diabetes mellitus type 2, Epilepsy, Guillain-Barré syndrome, Irritable bowel syndrome, Lupus, Metabolic syndrome, Multiple sclerosis, Myocardial infarction, Obesity, Obsessive-compulsive disorder, Panic disorder, Parkinson's disease, Psoriasis, Rheumatoid arthritis, Sarcoidosis, Schizophrenia, Stroke, Thromboangiitis obliterans, Tourette syndrome, Vasculitis. Still additional disease states or conditions which can be treated by compounds according to the present invention include aceruloplasminemia, Achondrogenesis type II, achondroplasia, Acrocephaly, Gaucher disease type 2, acute intermittent porphyria, Canavan disease, Adenomatous Polyposis Coli, ALA dehydratase deficiency, adenylosuccinate lyase deficiency, Adrenogenital syndrome, Adrenoleukodystrophy, ALA-D porphyria, ALA dehydratase deficiency, Alkaptonuria, Alexander disease, Alkaptonuric ochronosis, alpha 1-antitrypsin deficiency, alpha- 1 proteinase inhibitor, emphysema, amyotrophic lateral sclerosis Alstrém syndrome, Alexander disease, Amelogenesis imperfecta, ALA dehydratase deficiency, Anderson-Fabry disease, androgen insensitivity syndrome, Anemia Angiokeratoma Corporis Diffusum, Angiomatosis retinae (von Hippel-Lindau disease) Apert syndrome, Arachnodactyly (Marfan syndrome), Stickler syndrome, Arthrochalasis multiplex congenital (Ehlers-Danlos syndrome#arthrochalasia type) ataxia telangiectasia, Rett syndrome, primary pulmonary hypertension, Sandhoff disease, neurofibromatosis type II, Beare-Stevenson cutis gyrata syndrome, Mediterranean fever, familial, Benjamin syndrome, beta-thalassemia, Bilateral Acoustic Neurofibromatosis (neurofibromatosis type II), factor V Leiden thrombophilia, Bloch-Sulzberger syndrome (incontinentia pigmenti), Bloom syndrome, X-linked sideroblastic anemia, Bonnevie-Ullrich syndrome (Turner syndrome), Bourneville disease (tuberous sclerosis), prion disease, Birt-Hogg-Dubé syndrome, Brittle bone disease (osteogenesis imperfecta), Broad Thumb-Hallux syndrome (Rubinstein-Taybi syndrome), Bronze Diabetes / Bronzed Cirrhosis (hemochromatosis), Bulbospinal muscular atrophy (Kennedy's disease), Burger-Grutz syndrome (lipoprotein lipase deficiency), CGD Chronic granulomatous disorder, Campomelic dysplasia, biotinidase deficiency, Cardiomyopathy (Noonan syndrome), Cri du chat, CAVD (congenital absence of the vas deferens), Caylor cardiofacial syndrome (CBAVD), CEP (congenital erythropoietic porphyria), cystic fibrosis, congenital hypothyroidism, Chondrodystrophy syndrome (achondroplasia), otospondylomegaepiphyseal dysplasia, Lesch-Nyhan syndrome, galactosemia, Ehlers-Danlos syndrome, Thanatophoric dysplasia, Coffin-Lowry syndrome, Cockayne syndrome, (familial adenomatous polyposis), Congenital erythropoietic porphyria, Congenital heart disease, Methemoglobinemia / Congenital methaemoglobinaemia, achondroplasia, X-linked sideroblastic anemia, Connective tissue disease, Conotruncal anomaly face syndrome, Cooley's Anemia (beta-thalassemia), Copper storage disease (Wilson's disease), Copper transport disease (Menkes disease), hereditary coproporphyria, Cowden syndrome, Craniofacial dysarthrosis (Crouzon syndrome), Creutzfeldt-Jakob disease (prion disease), Cockayne syndrome, Cowden syndrome, Curschmann-Batten-Steinert syndrome (myotonic dystrophy), Beare-Stevenson cutis gyrata syndrome, primary hyperoxaluria, spondyloepimetaphyseal dysplasia (Strudwick type), muscular dystrophy, Duchenne and Becker types (DBMD), Usher syndrome, Degenerative nerve diseases including de Grouchy syndrome and Dejerine-Sottas syndrome, developmental disabilities, distal spinal muscular atrophy, type V, androgen insensitivity syndrome, Diffuse Globoid Body Sclerosis (Krabbe disease), Di George's syndrome, Dihydrotestosterone receptor deficiency, androgen insensitivity syndrome, Down syndrome, Dwarfism, erythropoietic protoporphyria Erythroid 5-aminolevulinate synthetase deficiency, Erythropoetic porphyria, erythropoietic protoporphyria, erythropoietic uroporphyria, Friedreich's ataxia-familial paroxysmal polyserositis, porphyria cutanea tarda, familial pressure sensitive neuropathy, primary pulmonary hypertension (PPH), Fibrocystic disease of the pancreas, fragile X syndrome, galactosemia, genetic brain disorders, Giant cell hepatitis (Neonatal hemochromatosis), Gronblad-Strandberg syndrome (pseudoxanthoma elasticum), Gunther disease (congenital erythropoietic porphyria), haemochromatosis, Hallgren syndrome, sickle cell anemia, hemophilia, hepatoerythropoietic porphyria (HEP), Hippel-Lindau disease (von Hippel-Lindau disease), Huntington's disease, Hutchinson-Gilford progeria syndrome (progeria), Hyperandrogenism, Hypochondroplasia, Hypochromic anemia, Immune system disorders, including X-linked severe combined immunodeficiency, Insley-Astley syndrome, Jackson-Weiss syndrome, Joubert syndrome, Lesch-Nyhan syndrome, Jackson-Weiss syndrome, Kidney diseases, including hyperoxaluria, Klinefelter's syndrome, Kniest dysplasia, Lacunar dementia, Langer- Saldino achondrogenesis, ataxia telangiectasia, Lynch syndrome, Lysyl-hydroxylase deficiency, Machado-Joseph disease, Metabolic disorders, including Kniest dysplasia, Marfan syndrome, Movement disorders, Mowat-Wilson syndrome, cystic fibrosis, Muenke syndrome, Multiple neurofibromatosis, Nance-Insley syndrome, Nance-Sweeney chondrodysplasia, Niemann-Pick disease, Noack syndrome (Pfeiffer syndrome), Osler-Weber-Rendu disease, Peutz-Jeghers syndrome, Polycystic kidney disease, polyostotic fibrous dysplasia (McCune-Albright syndrome), Peutz-Jeghers syndrome, Prader-Labhart-Willi syndrome, hemochromatosis, primary hyperuricemia syndrome (Lesch-Nyhan syndrome), primary pulmonary hypertension, primary senile degenerative dementia, prion disease, progeria (Hutchinson Gilford Progeria Syndrome), progressive chorea, chronic hereditary (Huntington) (Huntington's disease), progressive muscular atrophy, spinal muscular atrophy, propionic acidemia, protoporphyria, proximal myotonic dystrophy, pulmonary arterial hypertension, PXE (pseudoxanthoma elasticum), Rb (retinoblastoma), Recklinghausen disease (neurofibromatosis type I), Recurrent polyserositis, Retinal disorders, Retinoblastoma, Rett syndrome, RFALS type 3, Ricker syndrome, Riley-Day syndrome, Roussy-Levy syndrome, severe achondroplasia with developmental delay and acanthosis nigricans (SADDAN), Li-Fraumeni syndrome, sarcoma, breast, leukemia, and adrenal gland (SBLA) syndrome, sclerosis tuberose (tuberous sclerosis), SDAT, SED congenital (spondyloepiphyseal dysplasia congenita), SED Strudwick (spondyloepimetaphyseal dysplasia, Strudwick type), SEDc (spondyloepiphyseal dysplasia congenita) SEMD, Strudwick type (spondyloepimetaphyseal dysplasia, Strudwick type), Shprintzen syndrome, Skin pigmentation disorders, Smith-Lemli-Opitz syndrome, South-African genetic porphyria (variegate porphyria), infantile-onset ascending hereditary spastic paralysis, Speech and communication disorders, sphingolipidosis, Tay-Sachs disease, spinocerebellar ataxia, Stickler syndrome, stroke, androgen insensitivity syndrome, tetrahydrobiopterin deficiency, beta-thalassemia, Thyroid disease, Tomaculous neuropathy (hereditary neuropathy with liability to pressure palsies), Treacher Collins syndrome, Triplo X syndrome (triple X syndrome), Trisomy 21 (Down syndrome), Trisomy X, VHL syndrome (von Hippel-Lindau disease), Vision impairment and blindness (Alstrom syndrome), Vrolik disease, Waardenburg syndrome, Warburg Sjo Fledelius Syndrome, Wolf- Hirschhorn syndrome, Wolff Periodic disease, Weissenbacher-Zweymiiller syndrome and Xeroderma pigmentosum, among others, In certain embodiments, a treatment is provided for treating multiple myeloma comprising administering to a patient an effective amount of a compound described herein, or a pharmaceutically acceptable salt, isotopic analog, or prodrug thereof, optionally in a pharmaceutically acceptable carrier to form a composition. In another embodiment, a compound described herein, or a pharmaceutically acceptable salt, isotopic analog, or prodrug thereof, optionally in a pharmaceutically acceptable carrier to form a composition, for use in a treatment of multiple myeloma, wherein the treatment comprises administering the compound to a patient. In certain embodiments, a treatment is provided for managing the progression of multiple myeloma comprising administering to a patient an effective amount of a compound described herein, or a pharmaceutically acceptable salt, isotopic analog, or prodrug thereof, optionally in a pharmaceutically acceptable carrier to form a composition. In another embodiment, a compound described herein, or a pharmaceutically acceptable salt, isotopic analog, or prodrug thereof, optionally in a pharmaceutically acceptable carrier to form a composition, for use in a treatment for managing the progression of multiple myeloma, wherein the treatment comprises administering the compound to a patient. Treatments are also provided for patients who have been previously treated for multiple myeloma but are non-responsive to standard therapies in addition to those who have not been previously treated. Additional treatments are provided for patients who have undergone surgery in an attempt to treat multiple myeloma in addition to those who have not undergone surgery. Treatments are also provided for patients who have previously undergone transplant therapy in addition to those who have not. In certain embodiments, the disorder treated by the present invention is a wild-type cancer, wherein the term “wild-type” refers to a cancer that has not developed resistance to a previously effective treatment (i.e. a relapsed cancer) and does not have any resistance imparting mutations (i.e. a refractory cancer). In certain embodiments, the disorder treated by the present invention is a relapsed cancer. In certain embodiments, the disorder treated by the present invention is a refractory cancer. In certain embodiments, the disorder treated by the present invention is a relapsed and refractory cancer. A compound described herein, for example, Compound 1 or a pharmaceutically acceptable salt thereof, can be administered in the treatment or management of multiple myeloma or Non- Hodgkin’s Lymphoma that is relapsed, refractory, or resistant. In some embodiments, the disorder is primary, secondary, tertiary, quadruply or quintuply relapsed. In certain embodiments, the compounds described herein may be used to reduce, maintain, or eliminate minimal residual disease (MRD). The types of multiple myeloma that may be treated with the compounds described herein include, but are not limited to: monoclonal gammopathy of undetermined significance (MGUS); low risk, intermediate risk, or high risk multiple myeloma; newly diagnosed multiple myeloma, including low risk, intermediate risk, or high risk newly diagnosed multiple myeloma); transplant eligible and transplant ineligible multiple myeloma; smoldering (indolent) multiple myeloma (including low risk, intermediate risk, or high risk smoldering multiple myeloma); active multiple myeloma; solitary plasmocytoma; plasma cell leukemia; central nervous system multiple myeloma; light chain myeloma; non-secretory myeloma; Immunoglobulin D myeloma; and Immunoglobulin E myeloma. In certain embodiments, a treatment is provided for managing multiple myeloma comprising administering to a patient an effective amount of a compound described herein, or a pharmaceutically acceptable salt, isotopic analog, or prodrug thereof, optionally in a pharmaceutically acceptable carrier to form a composition, as induction therapy. In certain embodiments, a treatment is provided for treating or managing multiple myeloma comprising administering to a patient an effective amount of a compound described herein, or a pharmaceutically acceptable salt, isotopic analog, or prodrug thereof, optionally in a pharmaceutically acceptable carrier to form a composition, as consolidation therapy. In certain embodiments, a method is provided for treating or managing multiple myeloma comprising administering to a patient an effective amount of a compound described herein, or a pharmaceutically acceptable salt, isotopic analog, or prodrug thereof, optionally in a pharmaceutically acceptable carrier to form a composition, as maintenance therapy. In certain embodiments, the multiple myeloma is plasma cell leukemia. In certain embodiments, the multiple myeloma is high risk multiple myeloma. In some embodiments, the high-risk multiple myeloma is relapsed or refractory. In certain embodiments, the high-risk multiple myeloma has relapsed within 12 months of the first treatment. In another embodiment, the high-risk multiple myeloma is characterized by genetic abnormalities, for example, one or more of del(17 / 17p) and t(14;16)(q32;q32). In some embodiments, the high risk multiple myeloma is relapsed or refractory to one, two or three previous treatments. In some embodiments, the multiple myeloma is transplant eligible newly diagnosed multiple myeloma. In other embodiments, the multiple myeloma is transplant ineligible newly diagnosed multiple myeloma. In some embodiments, the multiple myeloma shows early progression (for example less than 12 months) following initial treatment. In other embodiments, the multiple myeloma shows early progression (for example less than 12 months) following autologous stem cell transplant. In another embodiment, the multiple myeloma is refractory to lenalidomide. In another embodiment, the multiple myeloma is refractory to pomalidomide. In some such embodiments, the multiple myeloma is predicted to be refractory to pomalidomide (for example, by molecular characterization). In another embodiment, the multiple myeloma is relapsed or refractory to 3 or more treatments and was exposed to a proteasome inhibitor (for example, bortezomib, carfilzomib, ixazomib, oprozomib, or marizomib) and an immunomodulatory compound (for example thalidomide, lenalidomide, pomalidomide, iberdomide, or avadomide), or double refractory to a proteasome inhibitor and an immunomodulatory compound. In still other embodiments, the multiple myeloma is relapsed or refractory to 3 or more prior therapies, including for example, a CD38 monoclonal antibody (CD38 mAb, for example, daratumumab or isatuximab), a proteasome inhibitor (for example, bortezomib, carfilzomib, ixazomib, or marizomib), and an immunomodulatory compound (for example thalidomide, lenalidomide, pomalidomide, iberdomide, or avadomide) or double refractory to a proteasome inhibitor or immunomodulatory compound and a CD38 mAb. In still other embodiments, the multiple myeloma is triple refractory, for example, the multiple myeloma is refractory to a proteasome inhibitor (for example, bortezomib, carfilzomib, ixazomib, oprozomib or marizomib), an immunomodulatory compound (for example thalidomide, lenalidomide, pomalidomide, iberdomide, or avadomide), and one other active agent, as described herein. In certain embodiments, a treatment is provided for managing relapsed or refractory multiple myeloma in patients with impaired renal function or a symptom thereof comprising administering to a patient an effective amount of a compound described herein, or a pharmaceutically acceptable salt, isotopic analog, or prodrug thereof, optionally in a pharmaceutically acceptable carrier to form a composition. In another embodiment, a treatment is provided for managing relapsed or refractory multiple myeloma in frail patients comprising administering to a patient an effective amount of a compound described herein, or a pharmaceutically acceptable salt, isotopic analog, or prodrug thereof, optionally in a pharmaceutically acceptable carrier to form a composition, wherein the frail patient is characterized by ineligibility for induction therapy or intolerance to dexamethasone treatment. In other embodiments, the frail patient is elderly, for example, older than 65 years old. In another embodiment, a treatment is provided for managing fourth line relapsed or refractory multiple myeloma comprising administering to a patient an effective amount of a compound described herein, or a pharmaceutically acceptable salt, isotopic analog, or prodrug thereof, optionally in a pharmaceutically acceptable carrier to form a composition. In another embodiment, a treatment is provided for managing newly diagnosed, transplant- ineligible multiple myeloma comprising administering to a patient an effective amount of a compound described herein, or a pharmaceutically acceptable salt, isotopic analog, or prodrug thereof, optionally in a pharmaceutically acceptable carrier to form a composition. In another embodiment, a treatment is provided for managing newly diagnosed, transplant- ineligible multiple myeloma comprising administering to a patient an effective amount of a compound described herein, or a pharmaceutically acceptable salt, isotopic analog, or prodrug thereof, optionally in a pharmaceutically acceptable carrier to form a composition, as maintenance therapy after another therapy or transplant. In another embodiment, a treatment is provided for managing high risk multiple myeloma that is relapsed or refractory to one, two, or three previous treatments comprising administering to a patient an effective amount of a compound described herein, or a pharmaceutically acceptable salt, isotopic analog, or prodrug thereof, optionally in a pharmaceutically acceptable carrier to form a composition. In certain embodiments, the disorder treated by the present invention is a relapsed and / or refractory Non-Hodgkin’s Lymphoma. In certain embodiments, the disorder treated by the present invention is a relapsed Non-Hodgkin's Lymphoma. In certain embodiments, the disorder treated by the present invention is a refractory Non-Hodgkin's Lymphoma. In certain embodiments, the disorder treated by the present invention is a relapsed and refractory Non-Hodgkin's Lymphoma. In certain embodiments, the disorder treated by the present invention is a relapsed and / or refractory multiple myeloma. In certain embodiments, the disorder treated by the present invention is a relapsed multiple myeloma. In certain embodiments, the disorder treated by the present invention is a refractory multiple myeloma. In certain embodiments, the disorder treated by the present invention is a relapsed and refractory multiple myeloma. In certain embodiments, the disorder treated by the present invention is a relapsed and / or refractory peripheral T-cell lymphoma. In certain embodiments, the disorder treated by the present invention is a relapsed peripheral T-cell lymphoma. In certain embodiments, the disorder treated by the present invention is a refractory peripheral T-cell lymphoma. In certain embodiments, the disorder treated by the present invention is a relapsed and refractory peripheral T-cell lymphoma. In certain embodiments, Compound 1 is administered for the treatment of PTCL-NOS (i.e. PTCL that is not otherwise specified). In other embodiments Compound 1 is administered for the treatment of PTCL with a specified subtype for example anaplastic large cell lymphoma (ALCL), angioimmunoblastic T-Cell lymphoma (AITL), enteropathy-type T-cell lymphoma, or extranodal natural killer (NK) cell / T-cell lymphoma. In certain embodiments, the disorder treated by the present invention is a relapsed and / or refractory systemic anaplastic large cell lymphoma (ALK"). In certain embodiments, the disorder treated by the present invention is a relapsed systemic anaplastic large cell lymphoma (ALK). In certain embodiments, the disorder treated by the present invention is a refractory systemic anaplastic large cell lymphoma (ALK). In certain embodiments, the disorder treated by the present invention is a relapsed and refractory systemic anaplastic large cell lymphoma (ALK™). In certain embodiments, the disorder treated by the present invention is a relapsed and / or refractory systemic anaplastic large cell lymphoma (ALK"). In certain embodiments, the disorder treated by the present invention is a relapsed systemic anaplastic large cell lymphoma (ALK"). In certain embodiments, the disorder treated by the present invention is a refractory systemic anaplastic large cell lymphoma (ALK"). In certain embodiments, the disorder treated by the present invention is a relapsed and refractory systemic anaplastic large cell lymphoma (ALK"). In certain embodiments, the disorder treated by the present invention is a relapsed and / or refractory angioimmunoblastic T-cell lymphoma. In certain embodiments, the disorder treated by the present invention is a relapsed angioimmunoblastic T-cell lymphoma. In certain embodiments, the disorder treated by the present invention is a refractory angioimmunoblastic T-cell lymphoma. In certain embodiments, the disorder treated by the present invention is a relapsed and refractory angioimmunoblastic T-cell lymphoma. In certain embodiments, the disorder treated by the present invention is a relapsed and / or refractory anaplastic large cell lymphoma. In certain embodiments, the disorder treated by the present invention is a relapsed anaplastic large cell lymphoma. In certain embodiments, the disorder treated by the present invention is a refractory anaplastic large cell lymphoma. In certain embodiments, the disorder treated by the present invention is a relapsed and refractory anaplastic large cell lymphoma. In certain embodiments, the disorder treated by the present invention is a relapsed and / or refractory mantle cell lymphoma. In certain embodiments, the disorder treated by the present invention is a relapsed mantle cell lymphoma. In certain embodiments, the disorder treated by the present invention is a refractory mantle cell lymphoma. In certain embodiments, the disorder treated by the present invention is a relapsed and refractory mantle cell lymphoma. In certain embodiments, the disorder treated by the present invention is a relapsed and / or refractory follicular lymphoma. In certain embodiments, the disorder treated by the present invention is a relapsed follicular lymphoma. In certain embodiments, the disorder treated by the present invention is a refractory follicular lymphoma. In certain embodiments, the disorder treated by the present invention is a relapsed and refractory follicular lymphoma. In certain embodiments, the disorder treated by the present invention is a relapsed and / or refractory follicular T-cell lymphoma. In certain embodiments, the disorder treated by the present invention is a relapsed follicular T-cell lymphoma. In certain embodiments, the disorder treated by the present invention is a refractory follicular T-cell lymphoma. In certain embodiments, the disorder treated by the present invention is a relapsed and refractory follicular T-cell lymphoma. In certain embodiments, the disorder treated by the present invention is a relapsed and / or refractory peripheral T-cell lymphoma, In certain embodiments, the disorder treated by the present invention is a relapsed peripheral T-cell lymphoma. In certain embodiments, the disorder treated by the present invention is a refractory peripheral T-cell lymphoma. In certain embodiments, the disorder treated by the present invention is a relapsed and refractory peripheral T-cell lymphoma. In certain embodiments, the disorder treated by the present invention is a relapsed and / or refractory diffuse large B-cell lymphoma. In certain embodiments, the disorder treated by the present invention is a relapsed diffuse large B-cell lymphoma. In certain embodiments, the disorder treated by the present invention is a refractory diffuse large B-cell lymphoma. In certain embodiments, the disorder treated by the present invention is a relapsed and refractory diffuse large B-cell lymphoma. In certain embodiments, Compound 1 is administered to a patient in need thereof in an effective amount to treat follicular T-cell lymphoma. In certain embodiments, Compound 1 is administered to a patient in need thereof in an effective amount to treat angioimmunoblastic T-cell lymphoma. In certain embodiments, Compound 1 is administered to a patient in need thereof in an effective amount to treat systemic anaplastic large cell lymphoma (ALK"). In certain embodiments, Compound 1 is administered to a patient in need thereof in an effective amount to treat systemic anaplastic large cell lymphoma (ALK"). Additional examples of Non-Hodgkin’s Lymphomas that can be treated with a compound described herein include Double hit lymphoma, triple hit lymphoma, extranodal marginal zone B- cell lymphoma of MALT, extranodal NK / T-cell lymphoma, and myeloid-lineage lymphoma. Pharmacodynamic Dose Modification and Biomarkers In certain embodiments, the compound of the present invention is administered in an effective amount to treat a patient with a cereblon-mediated disorder comprising administering to the patient an effective amount of the compound and monitoring the concentration of a biomarker selected from IRF-1, caspase-1, caspase-3, caspase-7, cyclin D1, E2F1, ZFP91, SALL4, IRF-4, BLIMPI1, MYC, IL-2, T-cell activation and / or proliferation, BCMA, M-protein, PARP, BIM, survivin, IKZF1, IKZF3, ZFP91, WIZ, and / or IFN- vy or a combination thereof. In certain embodiments, the concentration of IRF-1 and / or caspase 3 increases upon treating a patient with a compound described herein. The size of the increase can be used to determine whether or not the dose of the compound described herein should be increased, decreased, or kept the same. For example, if the concentration of IRF-1 and / or caspase 3 increases by less than 1.25, 1.5, 1.75, or 2-fold then the physician may increase the dose of Compound 1 administered to a patient being treated for a lymphoma. In certain embodiments, the concentration of cyclin D and / or E2F 1 decreases upon treating a patient with a compound described herein. The size of the decrease can be used to determine whether or not the dose of the compound described herein should be increased, decreased, or kept the same. For example, if the concentration of cyclin D and E2F 1 decreases by less than 1.25, 1.5, 1.75, or 2-fold then the physician may increase the dose of Compound 1 administered to a patient being treated for a lymphoma. In certain embodiments, the concentration of cyclin D, E2F1, ZFP91, SALL4, IRF-4, BLIMPI, and / or MYC decreases upon treating a patient with a compound described herein. In certain embodiments, the patient has a lymphoma. The size of the decrease can be used to determine whether or not the dose of the compound described herein should be increased, decreased, or kept the same. In certain embodiments, the concentration of IL-2 and / or IFN- y increases upon treating a patient with a compound described herein. In certain embodiments, the patient has a myeloma. The size of the increase can be used to determine whether or not the dose of the compound described herein should be increased, decreased, or kept the same. In certain embodiments the concentration of the biomarker increases by about 3, 4, 5, 6, 7, or 8 fold upon delivery of an effective dose of a compound described herein, for example Compound 1. For example, as shown in Figure 51 the activity level of caspase-3 and caspase-7 is increased by more than 800% upon treatment of Compound 1. In certain embodiments the level of caspase 3 / 7 activity is assayed and if less than about 2, 3, 4, 5, 6, 7, or 8-fold then the dose of Compound 1 is increased. In certain embodiments the biomarker is STAT3. In certain embodiments the biomarker is Ki67. In certain embodiments the concentration of the biomarker decreases by about 3, 4, 5, 6, 7, or 8-fold upon delivery of an effective dose of a compound described herein, for example Compound 1. In certain embodiments, the patient treated with a compound selected from Compound 1, Compound 2, Compound 3, Compound 4, Compound 5, Compound 6, Compound 7, Compound 8, Compound 9, Compound 10, Compound 11, Compound 12, and Compound 13, is selected based on the concentration of a biomarker. For example, the patient treated with Compound 1 may be selected based on the concentration of a biomarker. In certain embodiments, the biomarker is selected from IKZF1, IKZF3, MYC, il2, INFy, TNFa, sFLC, and sSBCMA. In certain embodiments, the biomarker is selected from IRF-1, caspase-3, cyclin D1, E2F1, ZFP91, SALL4, IRF-4, BLIMP1, MYC, IL-2, and / or IFN-y. In certain embodiments the biomarker is a tumor immunity marker (e.g., a cytokine, tumor infiltrating lymphocyte, T-cell activation and / or proliferation, and B-cell markers such as BCMA or M-protein, or a combination thereof). In certain embodiments the biomarker is an apoptotic marker (e.g., total and / or cleaved caspase-1, caspase-3, caspase-7, PARP, BIM, or survivin, or a combination thereof). In certain embodiments the biomarker is a zinc finger protein (e.g., IKZF1, IKZF3, ZFP91, WIZ, or SALL4, or a combination thereof). Treatment Advantages In one aspect of the present invention a treatment described herein has one or more advantages over presently approved treatments of cancer, for example treatments of multiple myeloma or Non-Hodgkin’s Lymphoma. For example, Compound 1 or a pharmaceutically acceptable salt thereof as administered using the treatments described herein has a better outcome in one or more of the measures described below than currently approved treatments, for example thalidomide, pomalidomide or lenalidomide (see Examples 9 12 13 15-19, 26-31, and 35 demonstrating the superior efficacy of Compound 1 in multiple myeloma and Non-Hodgkin’s Lymphoma models). In certain embodiments the advantage provided by Compound 1 over currently known treatments is a decreased propensity to develop resistance. For example, mice that had developed resistance to treatment with pomalidomide still responded rapidly to treatment with Compound 1 (see Figure 40). Additionally, when treatment was withdrawn from mice for a long enough period for their tumors to regrow and rechallenged with Compound 1 the tumors still rapidly decreased in size (see Figure 33). In other embodiments the advantage over currently approved therapies is the ability to treat refractory tumors. For example, in mice doses of Compound 1 as low as 30 ng / kg were effective in the treatment of NCI-H929 tumors that were nonresponsive to 3,000 ng / kg dosing (see Figure 33). Additionally, across a panel of cell lines Compound 1 was consistently 2-3 magnitudes more potent than pomalidomide and even demonstrated efficacy against cells that were refractory to pomalidomide (see Figure 32). This effect is also demonstrated by tracking biomarkers concentration such as caspase 3 (see Figure 31). In other embodiments the advantage over currently approved therapies is a more rapid degradation of IKZF1 and IKZF3 and thus a more rapid treatment of cancer. For example, Compound 1 degrades more IKZF1 in one hour than pomalidomide degrades in two hours when dosed at the same concentration (see Figure 29). In certain embodiments, a treatment is provided for inducing a therapeutic response as assessed by the International Uniform Response Criteria (IURC) for Multiple Myeloma (described in Durie B. G. M; et al. “International uniform response criteria for multiple myeloma. Leukemia 2006, 10(10):1-7) in a patient having multiple myeloma comprising administering to the patient an effective amount of a compound described herein, or a pharmaceutically acceptable salt, isotopic analog, or prodrug thereof, optionally in a pharmaceutically acceptable carrier to form a composition. In another embodiment, a treatment is provided to achieve a stringent complete response, complete response, or very good partial response, as assessed by the IURC for Multiple Myeloma in a patient having multiple myeloma comprising administering to the patient an effective amount of a compound described herein, or a pharmaceutically acceptable salt, isotopic analog, or prodrug thereof, optionally in a pharmaceutically acceptable carrier to form a composition. In another embodiment, a treatment is provided to achieve an increase in overall survival, progression-free survival, event-free survival, time to process, or disease-free survival in a patient having multiple myeloma comprising administering to the patient an effective amount of a compound described herein, or a pharmaceutically acceptable salt, isotopic analog, or prodrug thereof, optionally in a pharmaceutically acceptable carrier to form a composition (see Examples 21 and 22 which demonstrate a dose dependent increase in overall survival in animal models). The advantages of Compound 1 can be further enhanced by administering an additional bioactive agent in combination therapy. For example, in mouse studies when Compound 1 was administered in a treatment regimen that included weekly dexamethasone it was far more efficacious than the same dose of Compound 1 or dexamethasone alone (see Figure 41). Treatment of IKZF1 / IKZF3 Mediated Cancers with Prominent Mutations In certain embodiments, a compound described herein is administered in an effective amount to treat a cancer that is mediated by a protein with one or more mutations, for example a multiple myeloma mediated by a protein with one or more mutations. In some embodiments, the compounds described herein may be administered in an effective amount in the treatment or management of multiple myeloma characterized by a genetic abnormality, for example but not limited to: Cyclin D translocations (for example, t(11;14)(q13;q32); 1(6;14)(p21;32); 1(12;14)(p13;q32); or t(6;20);); MMSET translocations (for example t(4;14)(p16,q32); MAF translocations (for example t(14;16)(q32;a32);, (20,22); 1(16;22)(q11;q13); or t(14;20)(q32;q11); or other chromosome factor (for example deletion of 17p13 or chromosome 13; del(17 / 17p), nonhyperdiploidy, and gain (1q)). In certain embodiments, the multiple myeloma has a p53 mutation. In certain embodiments, the p53 mutation is a Q331 mutation. In certain embodiments, the p53 mutation is a R273H mutation. In certain embodiments, the p53 mutation is a K132 mutation. In certain embodiments, the p53 mutation is a K132N mutation. In certain embodiments, the p53 mutation is a R337 mutation. In certain embodiments, the p53 mutation is a R337L mutation. In certain embodiments, the p53 mutation is a W146 mutation. In certain embodiments, the p53 mutation is a $261 mutation. In certain embodiments, the p53 mutation is a S261T mutation. In certain embodiments, the p53 mutation is a E286 mutation. In certain embodiments, the p53 mutation is a E286K mutation. In certain embodiments, the p53 mutation is a R175 mutation. In certain embodiments, the p53 mutation is a R175H mutation. In certain embodiments, the p53 mutation is a E258 mutation. In certain embodiments, the p53 mutation is a E258K mutation. In certain embodiments, the p53 mutation is a A161 mutation. In certain embodiments, the p53 mutation is a A161T mutation. In certain embodiments, the multiple myeloma has a homozygous deletion of p53. In certain embodiments, the multiple myeloma has a homozygous deletion of wild-type p53. In certain embodiments, the multiple myeloma has wild-type p53. In certain embodiments, the multiple myeloma shows activation of one or more oncogenic drivers. In certain embodiments, the one or more oncogenic drivers are selected from the group consisting of C-MAF, MAFB, FGFR3, MMset, Cyclin D1, and Cyclin D. In certain embodiments, the multiple myeloma shows activation of C-MAF. In certain embodiments, the multiple myeloma shows activation of MAFB. In certain embodiments, the multiple myeloma shows activation of FGFR3 and MMset. In certain embodiments, the multiple myeloma shows activation of C-MAF, FGFR3, and MMset. In certain embodiments, the multiple myeloma shows activation of Cyclin D1. In certain embodiments, the multiple myeloma shows activation of MAFB and Cyclin D1. In certain embodiments, the multiple myeloma shows activation of Cyclin D. In certain embodiments, the multiple myeloma has one or more chromosomal translocations. In certain embodiments, the chromosomal translocation is t(14;16). In certain embodiments, the chromosomal translocation is t(14;20). In certain embodiments, the chromosomal translocation is t(4; 14). In certain embodiments, the chromosomal translocations are t(4;14) and (14,16). In certain embodiments, the chromosomal translocation is t(11;14). In certain embodiments, the chromosomal translocation is 1(6;20). In certain embodiments, the chromosomal translocation is (20,22). In certain embodiments, the chromosomal translocations are 1(6;20) and t(20;22). In certain embodiments, the chromosomal translocation is t(16;22). In certain embodiments, the chromosomal translocations are t(14;16) and t(16;22). In certain embodiments, the chromosomal translocations are t(14:20) and t(11;14). In certain embodiments, the multiple myeloma has a Q331 p53 mutation, activation of C- MAF, and a chromosomal translocation at t(14; 16). In certain embodiments, the multiple myeloma has homozygous deletion of p33, activation of C-MAF, and a chromosomal translocation at t(14; 16). In certain embodiments, the multiple myeloma has a K132N p53 mutation, activation of MAFB, and a chromosomal translocation at t(14;20). In certain embodiments, the multiple myeloma has wild type p53, activation of FGFR3 and MMset, and a chromosomal translocation at t(4; 14). In certain embodiments, the multiple myeloma has wild type p53, activation of C-MAF, and a chromosomal translocation at t(14;16). In certain embodiments, the multiple myeloma has homozygous deletion of p53, activation of FGFR3, MMset, and C-MAF, and chromosomal translocations at t(4;14) and t(14;16). In certain embodiments, the multiple myeloma has homozygous deletion of p53, activation of Cyclin D1, and a chromosomal translocation at t(11;14). In certain embodiments, the multiple myeloma has a R337L p53 mutation, activation of Cyclin D1, and a chromosomal translocation at t(11;14). In certain embodiments, the multiple myeloma has a W146 p53 mutation, activation of FGFR3 and MMset, and a chromosomal translocation at t(4; 14). In certain embodiments, the multiple myeloma has a $261T p53 mutation, activation of MAFB, and chromosomal translocations at 1(6;20) and t(20;22). In certain embodiments, the multiple myeloma has a E286K p53 mutation, by activation of FGFR3 and MMset, and a chromosomal translocation at t(4; 14). In certain embodiments, the multiple myeloma has a R175H p53 mutation, activation of FGFR3 and MMset, and a chromosomal translocation at t(4; 14). In certain embodiments, the multiple myeloma has a E258K p53 mutation, activation of C-MAF, and chromosomal translocations at t(14;16) and t(16;22). In certain embodiments, the multiple myeloma has wild type p53, activation of MAFB and Cyclin D1, and chromosomal translocations at t(14,20) and t(11;14). In certain embodiments, the multiple myeloma has a A161T p53 mutation, activation of Cyclin D, and a chromosomal translocation at t(11;14). Patient Selection In certain embodiments, the patient treated with a compound described herein has received a prior treatment with an IMiD, for example thalidomide, lenalidomide, or pomalidomide. In certain embodiments, the patient treated with a compound described herein has received a prior treatment with an CD20 antibody for example rituximab, ocrelizumab, obinutuzumab, ofatumumab, ibritumomab, tositumomab, or ublituximab. In certain embodiments, the patient treated with a compound described herein has received a prior treatment with an CD38 antibody for example daratumumab or isatuximab. In certain embodiments, the patient treated with a compound described herein has received a prior treatment with an CD30 antibody for example brentuximab. In certain embodiments, the patient treated with a compound described herein has received a prior treatment with a BTK inhibitor for example ibrutinib, acalabrutinib, or zanubrutinib. In certain embodiments, the patient treated with a compound described herein has received a prior treatment with an alkylator for example cyclophosphomide, melphan, melphalan flufenamide, or bendamustine. In certain embodiments, the patient treated with a compound described herein has received a prior treatment with a proteasome inhibitor for example bortezomib, carfilzomib, or ixazomib. In certain embodiments, the patient treated with a compound described herein has received a prior treatment with a glucocorticoid, for example dexamethasone, predinisone, or methylprednisolone. In certain embodiments, the patient treated with a compound described herein has received a prior treatment with a bone-modifying agent, for example denosumab, zoledronic acid, or pamidronate. In certain embodiments, the patient treated with a compound described herein has received a prior treatment with a HDAC inhibitor, for example panobinostat, In certain embodiments, the patient treated with a compound described herein has received a prior treatment with a nuclear export inhibitor, for example selinexor. In certain embodiments, the patient treated for multiple myeloma has received at least 1, 2, 3, or 4 prior anti-myeloma or lymphoma regimens, for example lenalidomide, pomalidomide, a proteasome inhibitor, a glucocorticoid, or an anti-CD38 antibody. For example, a patient that has received at least 3 prior anti-myeloma regimens including at least two consecutive cycles of lenalidomide, pomalidomide, a proteasome inhibitor, a glucocorticoid, or an anti-CD38 antibody. In certain embodiments, the patient treated for multiple myeloma has a M-protein level of > about .5g / dL by serum protein electophoresis (sSPEP), >200mg / 24-hour urine collection by Urine Protein Electrophoresis (uPEP), Serum Free Light Chain (FLC) levels >100 mg / L involved light chain and an abnormal kappa / lambda (k / }) ratio in subjects without measurable serum or urine M- protein, and / or a serum IgA level > 0.50g / dL. In certain embodiments, the patient treated has peripheral t-cell lymphoma and has had at least one prior alkylator-based chemotherapy treatment. In certain embodiments, the patient treated has anaplastic large cell lymphoma (ALCL) and has had at least one prior alkylator-based chemotherapy treatment and also has received CD30 antibody therapy. In certain embodiments, the patient treated has mantle cell lymphoma and has had at least two prior lines of therapy, including a CD20 antibody and alkylator chemotherapy line, and a Bruton’s tyrosine kinase inhibitor. In certain embodiments, the patient treated has follicular lymphoma and has had at least two prior lines of therapy, including a CD20 antibody and alkylator chemotherapy line. In certain embodiments, the patient treated has diffuse large B-cell lymphoma and has had at least two prior lines of therapy, including a CD20 antibody therapy and has received a prior autologous bone marrow transplant (or is ineligible for bone marrow transplant). In certain embodiments, the patient treated for Non-Hodgkin’s Lymphoma has a lesion that can be measured in at least two dimensions with PET-CT, for example a lesion with a minimum measurement of at least about 15 mm in the longest diameter. In some embodiments, the patient to be treated by one of the compounds described herein has not be treated with multiple myeloma therapy prior to administration. In some embodiments, the patient to be treated by one of the compounds described herein has been treated by multiple myeloma therapy prior to administration. In some embodiments, the patient to be treated by one of the compounds described herein has developed drug resistant to the multiple myeloma therapy. In some embodiments, the patient to be treated by one of the compounds described herein has developed resistance to one, two, or three multiple myeloma therapies, wherein the therapies are selected from a CD38 antibody (CD38 mAB, for example, daratumumab or isatuximab), a proteasome inhibitor (for example, bortezomib, carfilzomib, ixazomib, or marizomib), and an immunomodulatory compound (for example thalidomide, lenalidomide, pomalidomide, iberdomide, or avadomide). The compounds described herein can be administered in an effective amount to treat a patient regardless of patient's age. In some embodiments, the patient is 18 years or older. In other embodiments, the patient is more than 18, 25, 35, 40, 45, 50, 55, 60, 65, or 70 years old. In other embodiments, the patient is less than 65 years old. In other embodiments, the patient is more than 65 years old. In certain embodiments, the patient is an elderly multiple myeloma patient, such as a patient older than 65 years old. In certain embodiments, the patient is an elderly multiple myeloma patient, such as a patient older than 75 years old. V. Combination Therapy Any of the compounds described herein can be administered in an effective amount alone or in combination to treat a host such as a human with a disorder as described herein. In certain embodiments, a compound described herein is administered with an additional bioactive agent. The term “bioactive agent” is used to describe an agent, other than the compound according to the present invention, which can be administered in combination or alternation with a compound of the present invention to achieve a desired result of therapy. In certain embodiments, the compound of the present invention and the bioactive agent are administered in a manner that they are active in vivo during overlapping time periods, for example, have time-period overlapping Cmax, Tmax, AUC or another pharmacokinetic parameter. In another embodiment, the compound of the present invention and the bioactive agent are administered to a host in need thereof that do not have overlapping pharmacokinetic parameter, however, one has a therapeutic impact on the therapeutic efficacy of the other. As used herein when a compound is administered in combination with another this combination can be as one dosage form or multiple dosage forms at the same time or different times. Additionally, the compounds administered in combination can be administered with different dosing schedules. For example the combination of Compound 1 with dexamethasone includes a treatment regimen where Compound 1 is administered once a day for 21 consecutive days in a 28 day treatment cycle and dexamethasone is administered once a week during the treatment cycle. In certain embodiments, Compound 1 is administered to a patient in need thereof in an effective amount in combination with one or more additional therapeutic agents described herein. In certain embodiments, Compound 2 is administered to a patient in need thereof in an effective amount in combination with one or more additional therapeutic agents described herein. In certain embodiments, Compound 3 is administered to a patient in need thereof in an effective amount in combination with one or more additional therapeutic agents described herein. In certain embodiments, Compound 4 is administered to a patient in need thereof in an effective amount in combination with one or more additional therapeutic agents described herein. In certain embodiments, Compound 5 is administered to a patient in need thereof in an effective amount in combination with one or more additional therapeutic agents described herein. In certain embodiments, Compound 6 is administered to a patient in need thereof in an effective amount in combination with one or more additional therapeutic agents described herein. In certain embodiments, Compound 7 is administered to a patient in need thereof in an effective amount in combination with one or more additional therapeutic agents described herein. In certain embodiments, Compound 8 is administered to a patient in need thereof in an effective amount in combination with one or more additional therapeutic agents described herein. In certain embodiments, Compound 9 is administered to a patient in need thereof in an effective amount in combination with one or more additional therapeutic agents described herein. In certain embodiments, Compound 10 is administered to a patient in need thereof in an effective amount in combination with one or more additional therapeutic agents described herein. In certain embodiments, Compound 11 is administered to a patient in need thereof in an effective amount in combination with one or more additional therapeutic agents described herein. In certain embodiments, Compound 12 is administered to a patient in need thereof in an effective amount in combination with one or more additional therapeutic agents described herein. In certain embodiments, Compound 13 is administered to a patient in need thereof in an effective amount in combination with one or more additional therapeutic agents described herein. Corticosteroids In certain embodiments, the compound of the present invention is administered in combination with a corticosteroid. In certain embodiments, the corticosteroid is dexamethasone. In certain embodiments, Compound 1 is administered with a corticosteroid. In certain embodiments, Compound 1 is administered with dexamethasone, for example in the dosage regimen shown below: Study Dosage en Route of Ao Soy alin Dose Frequenc; Administration Drug(s) Formulation Le quency Level(s) Compound 1 Capsule Table A QD 21 / 7 Oral Once / week < 75 years old (QW) on days Dexamethasone Tablet 40 mg Fe - oT = Oral 1,8, 15, Once / week > 75 vears old (QW) on days Dexamethasone Tablet 20 mg 13,15 Oral and 22 In certain aspects Compound 1 is dosed QD on a dosing 21 / 7 schedule for each 28-day cycle in combination with another bioactive agent, for example once a week dosing of dexamethasone. In certain embodiments, the dexamethasone dose for an adult < 75 years old is 40 mg QW on days 1, 8, 15, and 22 of a 28-day cycle. In certain embodiments, the dexamethasone dose for an adult > 75 years old is 20 mg QW on days 1, 8, 15, and 22 of a 28- day cycle. In certain embodiments, a compound described herein is administered in combination with a corticosteroid. Non-limiting examples of corticosteroids include dexamethasone, prednisone, fludrocortisone, hydrocortisone, cortisone, betamethasone, methylprednisolone. In certain embodiments, Compound 1 is administered in combination with a corticosteroid. In certain embodiments, Compound 2 is administered in combination with a corticosteroid. In certain embodiments, Compound 3 is administered in combination with a corticosteroid. In certain embodiments, Compound 4 is administered in combination with a corticosteroid. In certain embodiments, Compound 5 is administered in combination with a corticosteroid. In certain embodiments, Compound 6 is administered in combination with a corticosteroid. In certain embodiments, Compound 7 is administered in combination with a corticosteroid. In certain embodiments, Compound 8 is administered in combination with a corticosteroid. In certain embodiments, Compound 9 is administered in combination with a corticosteroid. In certain embodiments, Compound 10 is administered in combination with a corticosteroid. In certain embodiments, Compound 11 is administered in combination with a corticosteroid. In certain embodiments, Compound 12 is administered in combination with a corticosteroid. In certain embodiments, Compound 13 is administered in combination with a corticosteroid. In certain embodiments, the corticosteroid is dexamethasone. Additional non-limiting examples of corticosteroids include corticosterone, aldosterone, prednisolone, triamcinolone, budesonide, deflazacort, flugestone, fluorometholone, medrysone, prebediolone acetate, chloroprednisone, cloprednol, difluprednate, fluocinolone, fluperolone, fluperolone acetate, fluprednisolone, loteprednol, prednicarbate, tixocortol, alclometasone, alclometasone dipropionate, Dbeclometasone, clobetasol, clobetasone, clocortolone, desoximetasone, ditlorasone, diflorasone diacetate, difluocortolone, difluocortolone valerate, fluprednidene, fluprednidene acetate, fluticasone, fluticasone furoate, halometasone, meprednisone, mometasone, mometasone furoate, paramethasone, prednylidene, rimexolone, ulobetasol, amcinonide, ciclesonide, desonide, formocortal, fluclorolone, fluclorolone acetonide, fludroxycortide, flunisolide, fluocinolone, fluocinolone acetonide, fluocinonide, halcinonide, triamcinolone, triamcinolone acetonide, cortivazol, RU-28362, dexamethasone acefurate, dexamethasone acetate, dexamethasone cipecilate, dexamethasone diethylaminoacetate, dexamethasone dipropionate, dexamethasone isonicotinate, dexamethasone linoleate, dexamethasone metasulphobenzoate, dexamethasone palmitate, dexamethasone phosphate, dexamethasone pivalate, dexamethasone succinate, dexamethasone sulfate, dexamethasone tebutate, dexamethasone troxundate, and dexamethasone valerate. Kinase Inhibitors In certain embodiments, the bioactive agent is a kinase inhibitor, for example a Bruton’s tyrosine kinase (BTK) inhibitor. In certain embodiments, the kinase inhibitor is selected from a phosphoinositide 3-kinase (PI3K) inhibitor, a Bruton’s tyrosine kinase (BTK) inhibitor, or a spleen tyrosine kinase (Syk) inhibitor, or a combination thereof. In certain embodiments, the compound of the present invention is administered in combination with a BTK inhibitor. In certain embodiments, the BTK inhibitor is Ibrutinib. In certain embodiments, the embodiments the BTK inhibitor is Acalabrutinib. In certain embodiments, Compound 1 is administered in combination with a BTK inhibitor. In certain embodiments, Compound 1 is administered in combination BTK inhibitor is Zanubrutinib. In certain with Ibrutinib. In certain embodiments, Compound 1 is administered in combination with Zanubrutinib. In certain embodiments, Compound 1 is administered in combination with Acalabrutinib. In certain embodiments, Compound 2 is administered in combination with a BTK inhibitor. In certain embodiments, Compound 3 is administered in combination with a BTK inhibitor. In certain embodiments, Compound 4 is administered in combination with a BTK inhibitor. In certain embodiments, Compound 5 is administered in combination with a BTK inhibitor. In certain embodiments, Compound 6 is administered in combination with a BTK inhibitor. In certain embodiments, Compound 7 is administered in combination with a BTK inhibitor. In certain embodiments, Compound 8 is administered in combination with a BTK inhibitor. In certain embodiments, Compound 9 is administered in combination with a BTK inhibitor. In certain embodiments, Compound 10 is administered in combination with a BTK inhibitor. In certain embodiments, Compound 11 is administered in combination with a BTK inhibitor. In certain embodiments, Compound 12 is administered in combination with a BTK inhibitor. In certain embodiments, Compound 13 is administered in combination with a BTK inhibitor. In certain embodiments, the BTK inhibitor is selected from Ibrutinib, Zanubrutinib, and Acalabrutinib. \ Examples of BTK inhibitors include ibrutinib (also known as PCI-32765)(Imbruvica™)(1- [(3R)-3-[4-amino-3-(4-phenoxy-phenyl)pyrazolo[3,4-d]pyrimidin-1-yl]piperidin-1-yl]prop-2-en- 1-one), dianilinopyrimidine-based inhibitors such as AVL-101 and AVL-291 / 292 (N-(3-((5- fluoro-2-((4-(2-methoxyethoxy)phenyl)amino)pyrimidin-4-yl)amino)phenyl)acrylamide) (Avila Therapeutics) (see US Patent Publication No 2011 / 0117073, incorporated herein in its entirety), Dasatinib ([N-(2-chloro-6-methylphenyl)-2-(6-(4-(2-hydroxyethyl)piperazin-1-yl)-2- methylpyrimidin-4-ylamino)thiazole-5-carboxamide], LFM-A13 (alpha-cyano-beta-hydroxy- beta-methyl-N-(2,5-ibromophenyl) propenamide), GDC-0834 ([R-N-(3-(6-(4-(1,4-dimethyl-3- oxopiperazin-2-yl)phenylamino)-4-methyl-5-ox0-4,5-dihydropyrazin-2-yl)-2-methylphenyl)- 4,5,6,7-tetrahydrobenzo[b]thiophene-2-carboxamide], CGI-560 4-(tert-butyl)-N-(3-(8- (phenylamino)imidazo[1,2-a]pyrazin-6-yl)phenyl)benzamide, CGI-1746 (4-(tert-butyl)-N-(2- methyl-3-(4-methyl-6-((4-(morpholine-4-carbonyl)phenyl)amino)-5-oxo-4,5-dihydropyrazin-2- yl)phenyl)benzamide), CNX-774 (4-(4-((4-((3-acrylamidophenyl)amino)-5-fluoropyrimidin-2- yl)amino)phenoxy)-N-methylpicolinamide), CTA056 (7-benzyl-1-(3-(piperidin-1-yl)propyl)-2- (4-(pyridin-4-yl)phenyl)-1H-imidazo[4,5-g]quinoxalin-6(5H)-one), GDC-0834 ((R)-N-(3-(6-((4- (1,4-dimethyl-3-oxopiperazin-2-yl)phenyl)amino)-4-methyl-5-oxo-4,5-dihydropyrazin-2-yl)-2- methylphenyl)-4,5,6,7-tetrahydrobenzo[b]thiophene-2-carboxamide), GDC-0837 ((R)-N-(3-(6- ((4-(1,4-dimethyl-3-oxopiperazin-2-yl)phenyl)amino)-4-methyl-5-oxo0-4,5-dihydropyrazin-2-yl)- 2-methylphenyl)-4,5,6,7-tetrahydrobenzo[b]thiophene-2-carboxamide), HM-71224, ACP-196, ONO-4059 (Ono Pharmaceuticals), PRT062607 (4-((3-(2H-1,2,3-triazol-2-yl)phenyl)amino)-2- (((1R,28)-2-aminocyclohexyl)amino)pyrimidine-5-carboxamide hydrochloride), QL-47 (1-(1- acryloylindolin-6-y1)-9-(1-methyl- 1H-pyrazol-4-yl)benzo[h][ 1,6 naphthyridin-2(1H)-one), and RN486 (6-cyclopropyl-8-fluoro-2-(2-hydroxymethyl-3-{ 1-methyl-5-[5-(4-methyl-piperazin-1- yl)-pyridin-2-ylamino]-6-oxo-1,6-dihydro-pyridin-3-yl}-phenyl)-2H-isoquinolin-1-one), and other molecules capable of inhibiting BTK activity, for example those BTK inhibitors disclosed in Akinleye et ah, Journal of Hematology & Oncology, 2013, 6:59, the entirety of which is incorporated herein by reference. In certain embodiments, the BTK inhibitor is selected from acalabrutinib, spebrutinib, zanubrutinib, LOX0-305, evobrutinib, TG-1701, tolebrutinib, BIIB091, DZD-9008, HZ-A-018, orelabrutinib, ACO058TA, SN1011, rilzabrutinib, ARQ 531, DTRMWXHS-12, INJ-64264681, branebrutinib, and fenebrutinib. In certain embodiments, Compound 1 is administered in combination with an BTK inhibitor selected from acalabrutinib, spebrutinib, zanubrutinib, LOXO- 305, evobrutinib, TG-1701, tolebrutinib, BIIB091, DZD-9008, HZ-A-018, orelabrutinib, ACO058TA, SN1011, rilzabrutinib, ARQ 531, DTRMWXHS-12, JNJ-64264681, branebrutinib, and fenebrutinib. Examples of PI3 kinase inhibitors include but are not limited to Wortmannin, demethoxyviridin, perifosine, idelalisib, Pictilisib, Palomid 529, ZSTK474, PWT33597, CUDC- 907, and AEZS-136, duvelisib, GS-9820, BKM120, GDC-0032 (Taselisib) (2-[4-[2-(2-Isopropyl- 5-methyl-1,2,4-triazol-3-y1)-5,6-dihydroimidazo[ 1,2-d][1,4]benzoxazepin-9-yl]pyrazol-1-yl]-2- methylpropanamide), MLN-1117 ((2R)-1-Phenoxy-2-butanyl hydrogen (S)-methylphosphonate; or Methyl(oxo) {[(2R)-1-phenoxy-2-butanyl]oxy }phosphonium)), BYL-719 ((2S)-N1-[4-Methyl- 5-[2-(2,2,2-trifluoro-1,1-dimethylethyl)-4-pyridinyl]-2-thiazolyl]-1,2-pyrrolidinedicarboxamide), GSK2126458 (2,4-Difluoro-N-{2-(methyloxy)-5-[4-(4-pyridazinyl)-6-quinolinyl]-3- pyridinyl }benzenesulfonamide) (omipalisib), TGX-221 (()-7-Methyl-2-(morpholin-4-y1)-9-(1- phenylaminoethyl)-pyrido[l,2-a]-pyrimidin-4-one), GSK2636771 (2-Methyl-1-(2-methyl-3- (trifluoromethyl)benzyl)-6-morpholino-1H-benzo[d]imidazole-4-carboxylic acid dihydrochloride), KIN-193 ((R)-2~((1-(7-methyl-2-morpholino-4-oxo-4H-pyrido[ 1,2-a]pyrimidin-9- yl)ethyl)amino)benzoic acid), TGR-1202 / RP5264, GS-9820 ((S)- 1-(4-((2-(2-aminopyrimidin-5- yl)-7-methyl-4-mohydroxypropan- 1 -one), GS-1101 (5-fluoro-3-phenyl-2-([S)]-1-[9H-purin-6- ylamino]-propyl)-3H-quinazolin-4-one), AMG-319, GSK-2269557, SAR245409 (N-(4-(N-(3- ((3,5-dimethoxyphenyl)amino)quinoxalin-2-yl)sulfamoyl)phenyl)-3-methoxy-4 methylbenzamide), =~ BAY80-6946 (2-amino-N-(7-methoxy-8-(3-morpholinopropoxy)-2,3- dihydroimidazo[l,2-cJquinaz), AS 252424 (5-[1-[5-(4-Fluoro-2-hydroxy-phenyl)-furan-2-yl]- meth-(Z)-ylidene]-thiazolidine-2,4-dione), CZ 24832 (5-(2-amino-8-fluoro-[1,2,4]triazolo[l,5- a]pyridin-6-yl)-N-tert-butylpyridine-3-sulfonamide), Buparlisib (5-[2,6-Di(4-morpholinyl)-4- pyrimidinyl]-4-(trifluoromethyl)-2-pyridinamine), GDC-0941 (2-(IH-Indazol-4-yl)-6-[[4- (methylsulfonyl)-1-piperazinyl]methyl]-4-(4-morpholinyl)thieno[3,2-d]pyrimidine), GDC-0980 ((S)-1-(4-((2-(2-aminopyrimidin-5-yl)-7-methyl-4-morpholinothieno[3,2-d]pyrimidin-6 yl)methyl)piperazin-l-yl)-2-hydroxypropan-l-one (also known as RG7422)), SF1126 ((8S,148,178)-14-(carboxymethyl)-8-(3-guanidinopropyl)-17-(hydroxymethyl)-3,6,9,12,15- pentaoxo-1-(4-(4-oxo-8-phenyl-4H-chromen-2-yl)morpholino-4-ium)-2-oxa-7,10,13,16- tetraazaoctadecan-18-oate), PF-05212384 (N-[4-[[4-(Dimethylamino)-1- piperidinyl]carbonyl]phenyl]-N'-[4-(4,6-di-4-morpholinyl-l,3,5-triazin-2-yl)phenyl Jurea) (gedatolisib), LY3023414, BEZ235 (2-Methyl-2-{4-[3-methyl-2-0x0-8-(quinolin-3-yl)-2,3- dihydro-1H-imidazo[4,5-c]quinolin-1-yl]phenyl } propanenitrile) (dactolisib), XL-765 (N-(3-(N-(3- (3,5-dimethoxyphenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-3-methoxy-4-methylbenzamide), and GSK1059615 (5-[[4-(4-Pyridinyl)-6-quinolinyl]methylene]-2,4-thiazolidenedione), PX886 ([(3aR,6E,98,9aR,10R, 11a8)-6-[[bis(prop-2-enyl)amino]methylidene]-5-hydroxy-9- (methoxymethyl)-9a,11a-dimethyl-1,4,7-trioxo-2,3,3a,9,10,11-hexahydroindeno[4,5h]isochromen- 10-y1] acetate (also known as sonolisib)), LY294002, AZD8186, PF-4989216, pilaralisib, GNE- 317, PI-3065, PI-103, NU7441 (KU-57788), HS 173, VS-5584 (SB2343), CZC24832, TG100- 115, A66, YM201636, CAY10505, PIK-75, PIK-93, AS-605240, BGT226 (NVP-BGT226), AZD6482, voxtalisib, alpelisib, IC-87114, TGI100713, CH5132799, PKI-402, copanlisib (BAY 80-6946), XL 147, PIK-90, PIK-293, PIK-294, 3-MA (3-methyladenine), AS-252424, AS-604850, apitolisib (GDC-0980; RG7422), and the structure described in W02014 / 071109. Syk inhibitors include, for example, Cerdulatinib (4-(cyclopropylamino)-2-((4-(4- (ethylsulfonyl)piperazin-1-yl)phenyl)amino)pyrimidine-5-carboxamide), entospletinib (6-(1H- indazol-6-yl)-N-(4-morpholinophenyl)imidazo[1,2-a]pyrazin-8-amine), fostamatinib ([6-({5- Fluoro-2-[(3,4,5-trimethoxyphenyl)amino]-4-pyrimidinyl }amino)-2,2-dimethyl-3-o0xo0-2,3- dihydro-4H-pyrido[3,2-b][1,4]oxazin-4-ylJmethyl dihydrogen phosphate), fostamatinib disodium salt (sodium (6-((5-fluoro-2-((3,4,5-trimethoxyphenyl Jamino)pyrimidin-4-yl)amino)-2,2- dimethyl-3-oxo0-2H-pyrido[3,2-b][1,4]oxazin-4(3H)-yl)methyl phosphate), BAY 61-3606 (2-(7- (3,4-Dimethoxyphenyl)-imidazo[1,2-c]pyrimidin-5-ylamino)-nicotinamide HCI), R09021 (6- [(IR,2S)-2-Amino-cyclohexylamino]-4-(5,6-dimethyl-pyridin-2-ylamino)-pyridazine-3- carboxylic acid amide), imatinib (Gleevac; 4-[(4-methylpiperazin-1-yl)methyl]-N-(4-methyl-3- {[4-(pyridin-3-yl)pyrimidin-2-ylJamino}phenyl)benzamide), staurosporine, GSK143 (2- (((3R,4R)-3-aminotetrahydro-2H-pyran-4-yl)amino)-4-(p-tolylamino)pyrimidine-5- carboxamide), PP2 (1-(tert-butyl)-3-(4-chlorophenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine), PRT-060318 (2-(((1R,28)-2-aminocyclohexyl Jamino)-4-(m-tolylamino)pyrimidine-5- carboxamide), PRT-062607 (4-((3-(2H-1,2,3-triazol-2-yl)phenyl)amino)-2-(((1R,2S)-2- aminocyclohexyl)amino)pyrimidine-5-carboxamide hydrochloride), R112 (3.3'-((5- fluoropyrimidine-2,4-diyl)bis(azanediyl))diphenol), R348 (3-Ethyl-4-methylpyridine), R406 (6- ((5-fluoro-2-((3,4,5-trimethoxyphenyl)amino)pyrimidin-4-ylJamino)-2,2-dimethyl-2H- pyrido[3,2-b][1,4]oxazin-3(4H)-one), piceatannol (3-Hydroxyresveratol), YM193306(see Singh et al. Discovery and Development of Spleen Tyrosine Kinase (SYK) Inhibitors, J. Med. Chem. 2012, 55, 3614-3643), 7-azaindole, piceatannol, ER-27319 (see Singh et al. Discovery and Development of Spleen Tyrosine Kinase (SYK) Inhibitors, J. Med. Chem. 2012, 55, 3614-3643 incorporated in its entirety herein), Compound D (see Singh et al. Discovery and Development of Spleen Tyrosine Kinase (SYK) Inhibitors, J. Med. Chem. 2012, 55, 3614-3643 incorporated in its entirety herein), PRT060318 (see Singh et al. Discovery and Development of Spleen Tyrosine Kinase (SYK) Inhibitors, J. Med. Chem. 2012, 55, 3614-3643 incorporated in its entirety herein), luteolin (see Singh et al. Discovery and Development of Spleen Tyrosine Kinase (SYK) Inhibitors, J. Med. Chem. 2012, 55, 3614-3643 incorporated in its entirety herein), apigenin (see Singh et al. Discovery and Development of Spleen Tyrosine Kinase (SYK) Inhibitors, J. Med. Chem. 2012, 55, 3614-3643 incorporated in its entirety herein), quercetin (see Singh et al. Discovery and Development of Spleen Tyrosine Kinase (SYK) Inhibitors, J. Med. Chem. 2012, 55, 3614-3643 incorporated in its entirety herein), fisetin (see Singh et al. Discovery and Development of Spleen Tyrosine Kinase (SYK) Inhibitors, J. Med. Chem. 2012, 55, 3614-3643 incorporated in its entirety herein), myricetin (see Singh et al. Discovery and Development of Spleen Tyrosine Kinase (SYK) Inhibitors, J. Med. Chem. 2012, 55, 3614-3643 incorporated in its entirety herein), morin (see Singh et al. Discovery and Development of Spleen Tyrosine Kinase (SYK) Inhibitors, J. Med. Chem. 2012, 55, 3614-3643 incorporated in its entirety herein). Proteasome Inhibitors In certain embodiments, the compound of the present invention is administered in combination with a proteasome inhibitor. In certain embodiments, the proteasome inhibitor is Bortezomib. In certain embodiments, the proteasome inhibitor is Ixazomib. In certain embodiments, the proteasome inhibitor is Carfilzomib. In certain embodiments, Compound 1 is administered in combination with a proteasome inhibitor. In certain embodiments, Compound 1 is administered in combination with Bortezomib. In certain embodiments, Compound 1 is administered in combination with Ixazomib. In certain embodiments, Compound 1 is administered in combination with Carfilzomib. In certain embodiments, Compound 1 is administered in combination with carfilzomib and daratumumab. In certain embodiments, Compound 2 is administered in combination with a proteasome inhibitor. In certain embodiments, Compound 3 is administered in combination with a proteasome inhibitor. In certain embodiments, Compound 4 is administered in combination with a proteasome inhibitor. In certain embodiments, Compound § is administered in combination with a proteasome inhibitor. In certain embodiments, Compound 6 is administered in combination with a proteasome inhibitor. In certain embodiments, Compound 7 is administered in combination with a proteasome inhibitor. In certain embodiments, Compound 8 is administered in combination with a proteasome inhibitor. In certain embodiments, Compound 9 is administered in combination with a proteasome inhibitor. In certain embodiments, Compound 10 is administered in combination with a proteasome inhibitor. In certain embodiments, Compound 11 is administered in combination with a proteasome inhibitor. In certain embodiments, Compound 12 is administered in combination with a proteasome inhibitor. In certain embodiments, Compound 13 is administered in combination with a proteasome inhibitor. In certain embodiments, the proteasome inhibitor is selected from Bortezomib, Ixazomib, VI.X1570, and Carfilzomib. Additional examples of proteasome inhibitors include ixazomib citrate, oprozomib, delanzomib, lactacystin, epoxomicin, MG132, MG-262, CEP-18770, NEOSH101, TQB3602, and KZR-616. In certain embodiments, Compound 1 is administered in combination with a proteasome inhibitor selected from ixazomib citrate, oprozomib, delanzomib, lactacystin, epoxomicin, MG132, MG-262, CEP-18770, NEOSH101, TOB3602, VI.X1570, and KZR-616. HDAC Inhibitors In certain embodiments, the compound of the present invention is administered in combination with an HDAC inhibitor, In certain embodiments, the HDAC inhibitor is Vorinostat. In certain embodiments, the HDAC inhibitor is Romidepsin. In certain embodiments, the HDAC inhibitor is Panobinostat. In certain embodiments, the HDAC inhibitor is Belinostat. In certain embodiments, Compound 1 is administered in combination with an HDAC inhibitor. In certain embodiments, Compound 1 is administered in combination with Vorinostat. In certain embodiments, Compound 1 is administered in combination with Romidepsin. In certain embodiments, Compound 1 is administered in combination with Panobinostat. In certain embodiments, Compound 1 is administered in combination with Belinostat. In certain embodiments, Compound 2 is administered in combination with a HDAC inhibitor. In certain embodiments, Compound 3 is administered in combination with a HDAC inhibitor. In certain embodiments, Compound 4 is administered in combination with a HDAC inhibitor. In certain embodiments, Compound 5 is administered in combination with a HDAC inhibitor. In certain embodiments, Compound 6 is administered in combination with a HDAC inhibitor. In certain embodiments, Compound 7 is administered in combination with a HDAC inhibitor. In certain embodiments, Compound 8 is administered in combination with a HDAC inhibitor. In certain embodiments, Compound 9 is administered in combination with a HDAC inhibitor. In certain embodiments, Compound 10 is administered in combination with a HDAC inhibitor. In certain embodiments, Compound 11 is administered in combination with a HDAC inhibitor. In certain embodiments, Compound 12 is administered in combination with a HDAC inhibitor. In certain embodiments, Compound 13 is administered in combination with a HDAC inhibitor. In certain embodiments, the HDAC inhibitor is selected from Vorinostat, Romidepsin, Panobinostat, and Belinostat. In certain embodiments, the HDAC inhibitor is selected from trapoxin B, sodium phenylbutyrate, tacedinaline, mocetinostat, BRD73954, BG45, domatinostat, cay10603, HPOB, TMP269, nexturastat A, Santacruzamate A, splitomicin, LMK-235, sodium butyrate, pivaloyloxymethyl butyrate, pyroxamide, abexinostat, resminostat, givinostat, quisinostat, Psammaplin A, KDS5170, 1-Alaninechlamydocin, depudecin, and CUDC-101. In certain embodiments, Compound 1 is administered in combination with an HDAC inhibitor selected from trapoxin B, sodium phenylbutyrate, tacedinaline, mocetinostat, BRD73954, BG45, domatinostat, cay10603, HPOB, TMP269, nexturastat A, Santacruzamate A, splitomicin, LMK-235, sodium butyrate, pivaloyloxymethyl butyrate, pyroxamide, abexinostat, resminostat, givinostat, quisinostat, Psammaplin A, KD5170, 1-Alaninechlamydocin, depudecin, and CUDC-101. IMiDs In certain embodiments, the compound of the present invention is administered in combination with an IMiD. In certain embodiments, the IMiD is thalidomide. In certain embodiments, the IMiD is lenalidomide. In certain embodiments, the IMiD is pomalidomide. In certain embodiments, Compound 1 is administered in combination with thalidomide. In certain embodiments, Compound 1 is administered in combination with lenalidomide. In certain embodiments, Compound 1 is administered in combination with pomalidomide. In certain embodiments, Compound 2 is administered in combination with an IMiD. In certain embodiments, Compound 3 is administered in combination with an IMiD. In certain embodiments, Compound 4 is administered in combination with an IMiD. In certain embodiments, Compound § is administered in combination with an IMiD. In certain embodiments, Compound 6 is administered in combination with an IMiD. In certain embodiments, Compound 7 is administered in combination with an IMiD. In certain embodiments, Compound 8 is administered in combination with an IMiD. In certain embodiments, Compound 9 is administered in combination with an IMiD. In certain embodiments, Compound 10 is administered in combination with an IMiD. In certain embodiments, Compound 11 is administered in combination with an IMD. In certain embodiments, Compound 12 is administered in combination with an IMiD. In certain embodiments, Compound 13 is administered in combination with an IMiD. In certain embodiments, the IMiD is selected from pomalidomide, thalidomide, and lenalidomide. In certain embodiments, the IMiD is CC-90009. In certain embodiments, the IMiD is CC-99282. In certain embodiments, the IMiD is CC-92480. In certain embodiments, Compound I is administered in combination with CC-90009. In certain embodiments, Compound 1 is administered in combination with CC-99282. In certain embodiments, Compound 1 is administered in combination with CC-92480. In certain embodiments, Compound 2, Compound 3, Compound 4, Compound 5, Compound 6, Compound 7, Compound 8, Compound 9, Compound 10, Compound 11, Compound 12, or Compound 13 is administered in combination with an IMiD. In certain embodiments, the IMiD is selected from CC-90009, CC-99282, and CC-92480. Antibodies In certain embodiments, the compound of the present invention is administered in combination with an antibody targeting CD20, CD30, or CD38. In certain embodiments, the targeted antibody is Rituximab. In certain embodiments, the targeted antibody is Daratumumab. In certain embodiments, the targeted antibody is Elotuzumab. In certain embodiments, the targeted antibody is Isatuximab. In certain embodiments, Compound 1 is administered in combination with an antibody targeting CD20, CD30, or CD38. In certain embodiments, Compound 1 is administered in combination with Rituximab. In certain embodiments, Compound 1 is administered in combination with Daratumumab. In certain embodiments, Compound 1 is administered in combination with Elotuzumab. In certain embodiments, Compound 1 is administered in combination with Isatuximab. In certain embodiments, Compound 2 is administered in combination with an antibody targeting CD20, CD30, or CD38. In certain embodiments, Compound 3 is administered in combination with an antibody targeting CD20, CD30, or CD38. In certain embodiments, Compound 4 is administered in combination with an antibody targeting CD20, CD30, or CD38. In certain embodiments, Compound 5 is administered in combination with an antibody targeting CD20, CD30, or CD38. In certain embodiments, Compound 6 is administered in combination with an antibody targeting CD20, CD30, or CD38. In certain embodiments, Compound 7 is administered in combination with an antibody targeting CD20, CD30, or CD38. In certain embodiments, Compound 8 is administered in combination with an antibody targeting CD20, CD30, or CD38. In certain embodiments, Compound 9 is administered in combination with an antibody targeting CD20, CD30, or CD38. In certain embodiments, Compound 10 is administered in combination with an antibody targeting CD20, CD30, or CD38. In certain embodiments, Compound 11 is administered in combination with an antibody targeting CD20, CD30, or CD38. In certain embodiments, Compound 12 is administered in combination with an antibody targeting CD20, CD30, or CD38. In certain embodiments, Compound 13 is administered in combination with an antibody targeting CD20, CD30, or CD38. In certain embodiments, the targeted antibody is selected from Rituximab, Daratumumab, Elotuzumab, and Isatuximab. In certain embodiments, the compound of the present invention is administered in combination with an antibody-drug conjugate. In certain embodiments, the antibody-drug conjugate is Brentuximab vedotin. In certain embodiments, the antibody-drug conjugate is Ibritumomab tiuxetan. In certain embodiments, the antibody-drug conjugate is Mogamulizumab. In certain embodiments, the antibody-drug conjugate is Obinutuzumab. In certain embodiments, the antibody-drug conjugate is Polatuzumab vedotin. In certain embodiments, the antibody-drug conjugate is Belantamab mafodotin (GSK2857916). In certain embodiments, the antibody-drug conjugate is MEDI2228. In certain embodiments, the antibody-drug conjugate is CC-99712. In certain embodiments, Compound 1 is administered in combination with an antibody-drug conjugate. In certain embodiments, Compound 1 is administered in combination with Brentuximab vedotin. In certain embodiments, Compound 1 is administered in combination with Ibritumomab tiuxetan. In certain embodiments, Compound 1 is administered in combination with Mogamulizumab. In certain embodiments, Compound 1 is administered in combination with Obinutuzumab. In certain embodiments, Compound 1 is administered in combination with Polatuzumab vedotin. In certain embodiments, Compound 1 is administered in combination with Belantamab mafodotin (GSK2857916). In certain embodiments, Compound 1 is administered in combination with MEDI2228. In certain embodiments, Compound 1 is administered in combination with CC-99712. In certain embodiments, Compound 1 is administered in combination with tafasitamab. In certain embodiments, Compound 2 is administered in combination with an antibody- drug conjugate. In certain embodiments, Compound 3 is administered in combination with an antibody-drug conjugate. In certain embodiments, Compound 4 is administered in combination with an antibody-drug conjugate. In certain embodiments, Compound 5 is administered in combination with an antibody-drug conjugate. In certain embodiments, Compound 6 is administered in combination with an antibody-drug conjugate. In certain embodiments, Compound 7 is administered in combination with an antibody-drug conjugate. In certain embodiments, Compound 8 is administered in combination with an antibody-drug conjugate. In certain embodiments, Compound 9 is administered in combination with an antibody-drug conjugate. In certain embodiments, Compound 10 is administered in combination with an antibody-drug conjugate. In certain embodiments, Compound 11 is administered in combination with an antibody-drug conjugate. In certain embodiments, Compound 12 is administered in combination with an antibody-drug conjugate. In certain embodiments, Compound 13 is administered in combination with an antibody-drug conjugate. In certain embodiments, the antibody-drug conjugate is selected from Brentuximab vedotin, Ibritumomab tiuxetan, Mogamulizumab, Obinutuzumab, Polatuzumab vedotin, Belantamab mafodotin (GSK2857916), MEDI2228, and CCO9712. In certain embodiments, the compound of the present invention is administered in combination with a bispecific antibody. In certain embodiments, the bispecific antibody is PF- 06863135. In certain embodiments, the bispecific antibody is TNB-383B. In certain embodiments, the bispecific antibody is REGN5458. In certain embodiments, the bispecific antibody is JNJ- 64007957. In certain embodiments, Compound 1 is administered in combination with a bispecific antibody. In certain embodiments, Compound 1 is administered in combination with PF-06863135. In certain embodiments, Compound 1 is administered in combination with TNB-383B. In certain embodiments, Compound 1 is administered in combination with REGN5458. In certain embodiments, Compound 1 is administered in combination with JNJ-64007957. In certain embodiments, Compound 2 is administered in combination with a bispecific antibody. In certain embodiments, Compound 3 is administered in combination with a bispecific antibody. In certain embodiments, Compound 4 is administered in combination with a bispecific antibody. In certain embodiments, Compound 5 is administered in combination with a bispecific antibody. In certain embodiments, Compound 6 is administered in combination with a bispecific antibody. In certain embodiments, Compound 7 is administered in combination with a bispecific antibody. In certain embodiments, Compound 8 is administered in combination with a bispecific antibody. In certain embodiments, Compound 9 is administered in combination with a bispecific antibody. In certain embodiments, Compound 10 is administered in combination with a bispecific antibody. In certain embodiments, Compound 11 is administered in combination with a bispecific antibody. In certain embodiments, Compound 12 is administered in combination with a bispecific antibody. In certain embodiments, Compound 13 is administered in combination with a bispecific antibody. In certain embodiments, the bispecific antibody is selected from PF-06863135, TNB- 383B, REGNS5458, and JNJ-64007957. In certain embodiments, the compound of the present invention is administered in combination with a naked monoclonal antibody (mAb). In certain embodiments, the naked mAb is SEA-BCMA. In certain embodiments, Compound 1 is administered in combination with a naked mAb. In certain embodiments, Compound 1 is administered in combination with SEA-BCMA. In certain embodiments, Compound 2 is administered in combination with a naked mAb. In certain embodiments, Compound 3 is administered in combination with a naked mAb. In certain embodiments, Compound 4 is administered in combination with a naked mAb. In certain embodiments, Compound 5 is administered in combination with a naked mAb. In certain embodiments, Compound 6 is administered in combination with a naked mAb. In certain embodiments, Compound 7 is administered in combination with a naked mAb. In certain embodiments, Compound 8 is administered in combination with a naked mAb. In certain embodiments, Compound 9 is administered in combination with a naked mAb. In certain embodiments, Compound 10 is administered in combination with a naked mAb. In certain embodiments, Compound 11 is administered in combination with a naked mAb. In certain embodiments, Compound 12 is administered in combination with a naked mAb. In certain embodiments, Compound 13 is administered in combination with a naked mAb. In certain embodiments, the naked mAb is SEA-BCMA. Additional non-limiting examples of CD38 antibodies include felzartamab, GBR 1342, TAK-573, CID-103, OKT10, STI-6129, SGX301, and mezagitamab. In certain embodiments, Compound 1 is administered in combination with a CD38 antibody selected from felzartamab, GBR 1342, TAK-573, CID-103, OKT10, STI-6129, SGX301, TAK-079, and mezagitamab. CAR T-cell therapy In certain embodiments, the compound of the present invention is administered in combination with a CAR T-cell therapy. In certain embodiments, the CAR T-cell therapy is Axicabtagene ciloleucel. In certain embodiments, the CAR T-cell therapy is Tisagenlecleucel. In certain embodiments, the CAR T-cell therapy is Idecabtagene vicleucel (ide-cel; bb2121). In certain embodiments, the CAR T-cell therapy is LCAR-B38M (JNJ-4528; JNJ-68284528). In certain embodiments, the CAR T-cell therapy is P-BCMA-101. In certain embodiments, the CAR T-cell therapy is PBCAR269A. In certain embodiments, the CAR T-cell therapy is bb21217. In certain embodiments, the CAR T-cell therapy is JCARK 125 (orva-cel; orvacabtagene autoleucel). In certain embodiments, the CAR T-cell therapy is ALLO-715. In certain embodiments, the CAR T-cell therapy is Descartes-08. In certain embodiments, the CAR T-cell therapy is FCARH143. In certain embodiments, the CAR T-cell therapy is CT053. In certain embodiments, Compound 1 is administered in combination with a CAR T-cell therapy. In certain embodiments, Compound 1 is administered in combination with Axicabtagene ciloleucel. In certain embodiments, Compound 1 is administered in combination with Tisagenlecleucel. In certain embodiments, Compound 1 is administered in combination with Idecabtagene vicleucel (ide-cel; bb2121). In certain embodiments, Compound 1 is administered in combination with LCAR-B38M (JNJ-4528; JNJ-68284528). In certain embodiments, Compound 1 is administered in combination with P-BCMA-101. In certain embodiments, Compound 1 is administered in combination with PBCAR269A. In certain embodiments, Compound 1 is administered in combination with bb21217. In certain embodiments, Compound 1 is administered in combination with JCARK125 (orva-cel; orvacabtagene autoleucel). In certain embodiments, Compound 1 is administered in combination with ALLO-715. In certain embodiments, Compound 1 is administered in combination with Descartes-08. In certain embodiments, Compound 1 is administered in combination with FCARHI143. In certain embodiments, Compound 1 is administered in combination with CT053. In certain embodiments, Compound 2 is administered in combination with CAR T-cell therapy. In certain embodiments, Compound 3 is administered in combination with CAR T-cell therapy. In certain embodiments, Compound 4 is administered in combination with CAR T-cell therapy. In certain embodiments, Compound 5 is administered in combination with CAR T-cell therapy. In certain embodiments, Compound 6 is administered in combination with CAR T-cell therapy. In certain embodiments, Compound 7 is administered in combination with CAR T-cell therapy. In certain embodiments, Compound 8 is administered in combination with CAR T-cell therapy. In certain embodiments, Compound 9 is administered in combination with CAR T-cell therapy. In certain embodiments, Compound 10 is administered in combination with CAR T-cell therapy. In certain embodiments, Compound 11 is administered in combination with CAR T-cell therapy. In certain embodiments, Compound 12 is administered in combination with CAR T-cell therapy. In certain embodiments, Compound 13 is administered in combination with CAR T-cell therapy. In certain embodiments, the CAR T-cell therapy is selected from Axicabtagene ciloleucel, Tisagenlecleucel, Idecabtagene vicleucel (ide-cel; bb2121), LCAR-B38M (JNJ-4528; JNJ- 68284528), and P-BCMA-101. In certain embodiments, the CAR T-cell therapy is selected from PBCAR269A, bb21217, JCARK 125 (orva-cel; orvacabtagene autoleucel), ALLO-715, Descartes- 08, FCARH143, and CT053. In certain embodiments the CAR T-cell Therapy is selected from ALLO-715, bb21217, BCMA CAR-T, CD138 CAR-T, CD19 CAR-T, ciltacabtagene autoleucel, CS1 (SLAMF7) CAR- T, CTO053, Descartes-11, idecabtagene vicleucel, NKG2D CAR-T, orvacabtagene autoleucel, P- BCMA-101, and UCARTCS1. Cellular Therapy In certain embodiments, the compound of the present invention is administered in combination with a cellular therapy. In certain embodiments Compound 1 is used in combination with a cellular therapy. Non-limiting examples of cellular therapy include allo-HSCT, allo-NKT, auto-HSCT, and auto-NKT. T-cell Engagers In certain embodiments, the compound of the present invention is administered in combination with a bi-specific T-cell engagers (BiTEs). In certain embodiments, the BiTE is Blinatumomab. In certain embodiments, the BiTE is CC-93268. In certain embodiments, the BiTE is AMG 420. In certain embodiments, the BiTE is AMG 701. In certain embodiments, Compound . is administered in combination with a bi-specific T-cell engagers (BiTEs). In certain embodiments, Compound 1 is administered in combination with Blinatumomab. In certain embodiments, Compound 1 is administered in combination with AMG 420. In certain embodiments, Compound 1 is administered in combination with CC-93269. In certain embodiments, Compound 1 is administered in combination with AMG 701. In certain embodiments, Compound 2 is administered in combination with a BiTE. In certain embodiments, Compound 3 is administered in combination with a BiTE. In certain embodiments, Compound 4 is administered in combination with a BiTE. In certain embodiments, Compound 5 is administered in combination with a BiTE. In certain embodiments, Compound 6 is administered in combination with a BiTE. In certain embodiments, Compound 7 is administered in combination with a BiTE. In certain embodiments, Compound 8 is administered in combination with a BiTE. In certain embodiments, Compound 9 is administered in combination with a BiTE. In certain embodiments, Compound 10 is administered in combination with a BiTE. In certain embodiments, Compound 11 is administered in combination with a BITE. In certain embodiments, Compound 12 is administered in combination with a BiTE. In certain embodiments, Compound 13 is administered in combination with a BiTE. In certain embodiments, the BiTE is selected from Blinatumomab, AMG 420, CC-93269, and AMG 4701. In certain embodiments Compound 1 is used in combination with a bispecific antibody selected from AMG 420, AMG 701, BFCR4350A, blinatumomab, CC-93269, elranatamab, EM801, REGN5458, talquetamab, teclistamab, and TNB-383B. Immune Modulators Checkpoint Inhibitors In certain embodiments, the compound of the present invention is administered in combination with a checkpoint inhibitor. In certain embodiments, the compound of the present invention is administered in combination with a PD-1 checkpoint inhibitor. In certain embodiments, the compound of the present invention is administered in combination with a PD-L1 checkpoint inhibitor. In certain embodiments, the compound of the present invention is administered in combination with an IFNAR checkpoint inhibitor. In certain embodiments, the checkpoint inhibitor is Nivolumab. In certain embodiments, the checkpoint inhibitor is Pembrolizumab. In certain embodiments, the checkpoint inhibitor is Interferon alfa-2b. In certain embodiments, Compound 1 is administered in combination with a checkpoint inhibitor, In certain embodiments, Compound 1 is administered in combination with a PD-1 checkpoint inhibitor. In certain embodiments, Compound 1 is administered in combination with a PD-L1 checkpoint inhibitor. In certain embodiments, Compound 1 is administered in combination with an IFNAR checkpoint inhibitor. In certain embodiments, Compound 1 is administered in combination with Nivolumab. In certain embodiments, Compound 1 is administered in combination with Pembrolizumab. In certain embodiments, Compound 1 is administered in combination with Interferon alfa-2b. In certain embodiments, Compound 2 is administered in combination with a checkpoint inhibitor. In certain embodiments, Compound 3 is administered in combination with a checkpoint inhibitor. In certain embodiments, Compound 4 is administered in combination with a checkpoint inhibitor. In certain embodiments, Compound 5 is administered in combination with a checkpoint inhibitor. In certain embodiments, Compound 6 is administered in combination with a checkpoint inhibitor. In certain embodiments, Compound 7 is administered in combination with a checkpoint inhibitor. In certain embodiments, Compound 8 is administered in combination with a checkpoint inhibitor. In certain embodiments, Compound 9 is administered in combination with a checkpoint inhibitor. In certain embodiments, Compound 10 is administered in combination with a checkpoint inhibitor. In certain embodiments, Compound 11 is administered in combination with a checkpoint inhibitor. In certain embodiments, Compound 12 is administered in combination with a checkpoint inhibitor. In certain embodiments, Compound 13 is administered in combination with a checkpoint inhibitor. In certain embodiments, the checkpoint inhibitor is a PD-1 checkpoint inhibitor. In certain embodiments, the checkpoint inhibitor is a PD-L1 checkpoint inhibitor. In certain embodiments, the checkpoint inhibitor is an IFNAR checkpoint inhibitor. In certain embodiments, the checkpoint inhibitor is selected from Nivolumab, Pembrolizumab, and Interferon alfa-2b. PD-1 inhibitors that blocks the interaction of PD-1 and PD-L1 by binding to the PD-1 receptor, and in turn inhibit immune suppression include, for example, nivolumab (Opdivo), pembrolizumab (Keytruda), pidilizumab, AMP-224 (AstraZeneca and MedImmune), PF- 06801591 (Pfizer), MEDIO680 (AstraZeneca), PDR001 (Novartis), REGN2810 (Regeneron), SHR-12-1 (Jiangsu Hengrui Medicine Company and Incyte Corporation), TSR-042 (Tesaro), and the PD-L1 / VISTA inhibitor CA-170 (Curis Inc.). PD-L1 inhibitors that block the interaction of PD-1 and PD-L1 by binding to the PD-L1 receptor, and in turn inhibits immune suppression, include for example, atezolizumab (Tecentriq), durvalumab (AstraZeneca and MedImmune), KNO035 (Alphamab), and BMS-936559 (Bristol-Myers Squibb). CTLA-4 checkpoint inhibitors that bind to CTLA-4 and inhibits immune suppression include, but are not limited to, ipilimumab, tremelimumab (AstraZeneca and MedImmune), AGEN1884 and AGEN2041 (Agenus). LAG-3 checkpoint inhibitors, include, but are not limited to, BMS-986016 (Bristol-Myers Squibb), GSK2831781 (GlaxoSmithKline), IMP321 (Prima BioMed), LAG525 (Novartis), and the dual PD-1 and LAG-3 inhibitor MGDO13 (MacroGenics). An example of a TIM-3 inhibitor is TSR- 022 (Tesaro). In certain embodiments, the checkpoint inhibitor is selected from nivolumab / OPDIVO®; pembrolizumab / KEYTRUDA®; and pidilizumab / CT-011, MPDL3280A / RG7446; MEDI4736; MSB0010718C; BMS 936559, a PDL2 / g fusion protein such as AMP 224 or an inhibitor of B7- H3 (e.g., MGA271 ), B7-H4, BTLA, HVEM, TIM3, GAL9, LAG 3, VISTA, KIR, 2B4, CD160, CGEN-15049, CHK 1, CHK2, A2aR, B-7 family ligands, or a combination thereof. In certain embodiments, the PD-1 inhibitor is BGB-A317. In certain embodiments, the PD-L1 inhibitor is MED14736. In certain embodiments, the PD-L2 inhibitor is rHIgM12B7A. In certain embodiments, the checkpoint inhibitor is a B7 inhibitor, for example a B7-H3 inhibitor or a B7-H4 inhibitor. In certain embodiments, the B7-H3 inhibitor is MGA271. In certain embodiments, the checkpoint inhibitor is an OX40 agonist. In certain embodiments, the checkpoint inhibitor is an anti-OX40 antibody, for example anti-OX-40 or MEDI6469. In certain embodiments, the checkpoint inhibitor is a GITR agonist. In certain embodiments, the GITR agonist is an anti-GITR antibody, for example TRX518. In certain embodiments, the checkpoint inhibitor is a CD137 agonist. In certain embodiments, the CD137 agonist is an anti-CD137 antibody, for example PF-05082566. In certain embodiments, the checkpoint inhibitor is a CD40 agonist. In certain embodiments, the CD40 agonist is an anti-CD40 antibody, for example CF-870,893. In certain embodiments, the checkpoint inhibitor is an IDO inhibitor, for example INCB24360 or indoximod. In certain embodiments the checkpoint inhibitor is selected from atezolizumab, avelumab, durvalumab, nivolumab, and pembrolizumab. Additional Bioactive Agents In another embodiment, an active compounds described herein can be administered in an effective amount for the treatment of abnormal tissue of the male reproductive system such as prostate or testicular cancer, in combination or alternation with an effective amount of an androgen (such as testosterone) inhibitor including but not limited to a selective androgen receptor modulator, a selective androgen receptor degrader, a complete androgen receptor degrader, or another form of partial or complete androgen antagonist. In certain embodiments, the prostate or testicular cancer is androgen-resistant. Non-limiting examples of anti-androgen compounds are provided in WO 2011 / 156518 and US Patent Nos. 8,455,534 and 8,299,112. Additional non-limiting examples of anti-androgen compounds include: enzalutamide, apalutamide, cyproterone acetate, chlormadinone acetate, spironolactone, canrenone, drospirenone, ketoconazole, topilutamide, abiraterone acetate, and cimetidine. In certain embodiments, the bioactive agent is an ALK inhibitor. Examples of ALK inhibitors include but are not limited to Crizotinib, Alectinib, ceritinib, TAE684 (NVP-TAE684), GSK 1838705A, AZD3463, ASP3026, PF-06463922, entrectinib (RXDX-101), and AP26113. In certain embodiments, the bioactive agent is an EGFR inhibitor. Examples of EGFR inhibitors include erlotinib (Tarceva), gefitinib (Iressa), afatinib (Gilotrif), rociletinib (CO-1686), osimertinib (Tagrisso), olmutinib (Olita), naquotinib (ASP8273), nazartinib (EGF816), PF- 06747775 (Pfizer), icotinib (BPI-2009), neratinib (HKI-272; PB272); avitinib (AC0010), EAI045, tarloxotinib (TH-4000; PR-610), PF-06459988 (Pfizer), tesevatinib (XL647; EXEL-7647;, KD- 019), transtinib, WZ-3146, WZ8040, CNX-2006, and dacomitinib (PF-00299804; Pfizer). In certain embodiments, the bioactive agent is an HER-2 inhibitor. Examples of HER-2 inhibitors include trastuzumab, lapatinib, ado-trastuzumab emtansine, and pertuzumab. In certain embodiments, the bioactive agent is a CD20 inhibitor. Examples of CD20 inhibitors include obinutuzumab, rituximab, fatumumab, ibritumomab, tositumomab, and ocrelizumab. In certain embodiments, the bioactive agent is a JAK3 inhibitor. Examples of JAK3 inhibitors include tasocitinib. In certain embodiments the bioactive agent is a JAK inhibitor, for example ruxolitinib. In certain embodiments, the bioactive agent is a BCL-2 inhibitor. Examples of BCL-2 inhibitors include venetoclax, ABT-199 (4-[4-[[2-(4-Chlorophenyl)-4,4-dimethylcyclohex-1-en- 1-yl]methyl]piperazin-l-yl]-N-[[3-nitro-4-[[(tetrahydro-2H-pyran-4- yl)methyl]amino]phenyl]sulfonyl]-2-[(IH- pyrrolo[2,3-b]pyridin-5-yl)oxy]benzamide), ABT-737 (4-[4-[[2-(4-chlorophenyl)phenylJmethyl]piperazin-1-yl]-N-[4- [[(2R)-4-(dimethylamino)-1- phenylsulfanylbutan-2-yl] amino]-3- nitrophenyl]sulfonylbenzamide) (navitoclax), ABT-263 ((R)-4-(4-((4'-chloro-4,4-dimethyl-3,4,5,6-tetrahydro-[1, I'-biphenyl]-2-yl)methyl)piperazin-1-yl)- N-((4-((4-morpholino-1-(phenylthio)butan-2-yl)amino)- 3((trifluoromethyl)sulfonyl)phenyl)sulfonyl)benzamide), GX15-070 (obatoclax mesylate, (2Z)-2- [(5Z)-5-[(3,5- dimethyl-IH-pyrrol-2-yl)methylidene]-4-methoxypyrrol-2-ylidene]indole; methanesulfonic ~~ acid))), 2-methoxy-antimycin ~~ A3, YCI137 (4-(4,9-dioxo-4,9- dihydronaphtho[2,3-d]thiazol-2-ylamino)-phenyl ester), pogosin, ethyl 2-amino-6-bromo-4-(1- cyano-2-ethoxy-2-oxoethyl)-4H-chromene-3-carboxylate, Nilotinib-d3, TW-37 (N-[4-[[2-(1,1- Dimethylethyl)phenyl]sulfonyl]phenyl]-2,3,4-trihydroxy-5-[[2-(1- methylethyl)phenyl]methyl]benzamide), Apogossypolone (ApoG2), HA14-1, AT101, sabutoclax, gambogic acid, or G3139 (Oblimersen). In certain embodiments the bioactive agent is venetoclax. In certain embodiments, the bioactive agent is a MEK inhibitor. MEK inhibitors are well known, and include, for example, trametinib / GSK1120212 (N-(3-{3-Cyclopropyl-5-[(2-fluoro-4- iodophenyl)amino]-6,8-dimethyl-2,4,7-trioxo-3,4,6,7-tetrahydropyrido[4,3-d]pyrimidin-1(2H- yl}phenyl)acetamide), selumetinib (6-(4-bromo-2-chloroanilino)-7-fluoro-N-(2-hydroxyethoxy)- 3-methylbenzimidazole-5-carboxamide), pimasertib / AS703026 / MSC 1935369 ((S)-N-(2,3- dihydroxypropyl)-3-((2-fluoro-4- iodophenyl)amino)isonicotinamide), XL-518 / GDC-0973 (1- ({3,4-difluoro-2-[(2-fluoro-4- iodophenyl)amino]phenyl}carbonyl)-3-[(2S)-piperidin-2- yl]azetidin-3-ol), refametinib / BAY869766 / RDEAI 19 (N-(3,4-difluoro-2-(2-fluoro-4- iodophenylamino)-6-methoxyphenyl)-1-(2,3-dihydroxypropyl)cyclopropane-1-sulfonamide), PD-0325901 (N-[(2R)-2,3-Dihydroxypropoxy]-3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]- benzamide), TAK733 ((R)-3-(2,3-Dihydroxypropyl)-6-fluoro-5-(2-fluoro-4-iodophenylamino)-8- methylpyrido[2,3-d]pyrimidine-4,7(3H,8H)-dione), MEK162 / ARRY438162 (5-[(4-Bromo-2- fluorophenyl)amino]-4-fluoro-N-(2- hydroxyethoxy)-1-methyl-1H-benzimidazole-6- carboxamide), RO05126766 (3-[[3-Fluoro-2- (methylsulfamoylamino)-4-pyridyl]methyl]-4- methyl-7-pyrimidin-2-yloxychromen-2-one), WX-554, R04987655 / CH4987655 (3,4-difluoro-2- ((2-fluoro-4-iodophenyl)amino)-N-(2-hydroxyethoxy)-5-((3-ox0-1,2-oxazinan- 2yl)methyl)benzamide), or AZD8330 (2-((2-fluoro-4-iodophenyl)amino)-N-(2 hydroxyethoxy)- 1,5-dimethyl-6-oxo-1,6-dihydropyridine-3-carboxamide), U0126-EtOH, PD184352 (CI-1040), GDC-0623, BI-847325, cobimetinib, PD98059, BIX 02189, BIX 02188, binimetinib, SL-327, TAK-733, PD318088. In certain embodiments, the bioactive agent is a Raf inhibitor. Raf inhibitors are known and include, for example, Vemurafinib (N-[3-[[5-(4-Chlorophenyl)-1H-pyrrolo[2,3-b]pyridin-3- yl]carbonyl]-2,4-difluorophenyl]-1-propanesulfonamide), sorafenib tosylate (4-[4-[[4-chloro-3- (trifluoromethyl)phenyl]carbamoylamino]phenoxy]-N-methylpyridine-2-carboxamide;4- methylbenzenesulfonate), AZ628 (3-(2-cyanopropan-2-yl)-N-(4-methyl-3-(3-methyl-4-oxo-3,4- dihydroquinazolin-6-ylamino)phenyl)benzamide), NVP-BHG712 (4-methyl-3-(1-methyl-6- (pyridin-3-yl)-1H-pyrazolo[3,4-d]pyrimidin-4-ylamino)-N-(3- (trifluoromethyl)phenyl)benzamide), RAF-265 (1-methyl-5-[2-[5-(trifluoromethyl)-1H-imidazol- 2-yl]pyridin-4-yl]oxy-N-[4-(trifluoromethyl)phenyl]benzimidazol-2-amine), 2-Bromoaldisine (2-Bromo-6,7-dihydro-1H,5H-pyrrolo[2,3-c]azepine-4,8-dione), Raf Kinase Inhibitor IV (2- chloro-5-(2-phenyl-5-(pyridin-4-yl)-1H-imidazol-4-yl)phenol), Sorafenib N-Oxide (4-[4-[[[[4- Chloro-3(trifluoroMethyl)phenyl]aMino]carbonyl JaMino]phenoxy]-N-Methyl- 2pyridinecarboxaMide 1-Oxide), PLX-4720, dabrafenib (GSK2118436), GDC-0879, RAF265, AZ 628, SB590885, ZM336372, GW5074, TAK-632, CEP-32496, LY3009120, and GX818 (Encorafenib). In certain embodiments, the bioactive agent is an AKT inhibitor, including but not limited to, MK-2206, GSK690693, Perifosine, (KRX-0401), GDC-0068, Triciribine, AZD5363, Honokiol, PF-04691502, and Miltefosine, a FLT-3 inhibitor, including but not limited to, P406, Dovitinib, Quizartinib (AC220), Amuvatinib (MP-470), Tandutinib (MLN518), ENMD-2076, and KW-2449, or a combination thereof. In certain embodiments, the bioactive agent is an mTOR inhibitor. Examples of mTOR inhibitors include but are not limited to rapamycin and its analogs, everolimus (Afinitor), temsirolimus, ridaforolimus, sirolimus, and deforolimus. Examples of MEK inhibitors include but are not limited to tametinib / GSKI120212 (N-(3-{3-Cyclopropyl-5-[(2-fluoro-4- iodophenyl)amino]-6,8-dimethyl-2,4,7-trioxo-3,4,6,7-tetrahydropyrido[4,3-d]pyrimidin-1(2H- yl}phenyl)acetamide), selumetinob (6-(4-bromo-2-chloroanilino)-7-fluoro-N-(2-hydroxyethoxy)- 3-methylbenzimidazole-5-carboxamide), pimasertib / AS703026 / MSC1935369 ((S)-N-(2,3- dihydroxypropyl)-3-((2-fluoro-4-iodophenyl)amino)isonicotinamide), XL-518 / GDC-0973 (1- ({3,4-difluoro-2-[(2-fluoro-4- iodophenyl)amino]phenyl} carbonyl)-3-[(2S)-piperidin-2- yl]azetidin-3-ol) (cobimetinib), refametinib / BAY869766 / RDEAL19 (N-(3,4-difluoro-2-(2-fluoro- 4-iodophenylamino)-6-methoxyphenyl)-1-(2,3-dihydroxypropyl)cyclopropane-1-sulfonamide), PD-0325901 (N-[(2R)-2,3-Dihydroxypropoxy]-3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]- benzamide), TAK733 ((R)-3-(2,3-Dihydroxypropyl)-6-fluoro-5-(2-fluoro-4-iodophenylamino)-8- methylpyrido[2,3d]pyrimidine-4,7(3H,8H)-dione), MEK162 / ARRY438162 (5-[(4-Bromo-2- fluorophenyl)amino]-4-fluoro-N-(2-hydroxyethoxy)-1-methyl-1H-benzimidazole-6 carboxamide), R05126766 (3-[[3-Fluoro-2-(methylsulfamoylamino)-4-pyridylJmethyl]-4- methyl-7-pyrimidin-2-yloxychromen-2-one), WX-554, R04987655 / CH4987655 (3,4-difluoro-2- ((2-fluoro-4-iodophenyl)amino)-N-(2-hydroxyethoxy)-5-((3-oxo-1,2-0xazinan-2 yl)methyl)benzamide), or AZD8330 (2-((2-fluoro-4-iodophenyl)amino)-N-(2-hydroxyethoxy)- 1,5-dimethyl-6-oxo-1,6-dihydropyridine-3-carboxamide). In certain embodiments, the bioactive agent is a RAS inhibitor. Examples of RAS inhibitors include but are not limited to Reolysin and siG12D LODER. In certain embodiments, the bioactive agent is a HSP inhibitor. HSP inhibitors include but are not limited to Geldanamycin or 17-N-Allylamino-17-demethoxygeldanamycin (17AAG), and Radicicol In certain embodiments the bioactive agent is a biphosphonate. Examples of biphosphonates include but are not limited to clodronate, pamidronate, and zoledronic acid. Additional bioactive compounds include, for example, everolimus, trabectedin, abraxane, TLK 286, AV-299, DN-101, pazopanib, GSK690693, RTA 744, ON 0910.Na, AZD 6244 (ARRY- 142886), AMN-107, TKI-258, GSK461364, AZD 1152, enzastaurin, vandetanib, ARQ-197, MK- 0457, MLN8054, PHA-739358, R-763, AT-9263, a FLT-3 inhibitor, a VEGFR inhibitor, an aurora kinase inhibitor, a PIK-1 modulator, an HDAC inhbitor, a ¢-MET inhibitor, a PARP inhibitor, a Cdk inhibitor, an IGFR-TK inhibitor, an anti-HGF antibody, a focal adhesion kinase inhibitor, a Map kinase (mek) inhibitor, a VEGF trap antibody, pemetrexed, panitumumab, amrubicin, oregovomab, Lep-etu, nolatrexed, azd2171, batabulin, ofatumumab, zanolimumab, edotecarin, tetrandrine, rubitecan, tesmilifene, oblimersen, ticilimumab, ipilimumab, gossypol, Bio 111, 131- I-TM-601, ALT-110, BIO 140, CC 8490, cilengitide, gimatecan, IL13-PE38QQR, INO 1001, IPdR1 KRX-0402, lucanthone, LY317615, neuradiab, vitespan, Rta 744, Sdx 102, talampanel, atrasentan, Xr 311, romidepsin, ADS-100380, sunitinib, S-fluorouracil, vorinostat, etoposide, gemcitabine, doxorubicin, liposomal doxorubicin, 5'-deoxy-5-fluorouridine, vincristine, temozolomide, ZK-304709, seliciclib; PD0325901, AZD-6244, capecitabine, L-Glutamic acid, N- [4-[2-(2-amino-4,7-dihydro-4-oxo-1H-pyrrolo[2,3-d]pyrimidin-5-yl)ethyl]benzoyl]-, disodium salt, heptahydrate, camptothecin, PEG-labeled irinotecan, tamoxifen, toremifene citrate, anastrazole, exemestane, letrozole, DES(diethylstilbestrol), estradiol, estrogen, conjugated estrogen, bevacizumab, IMC-1C11, CHIR-258); 3-[5-(methylsulfonylpiperadinemethyl)-indolyl- quinolone, vatalanib, AG-013736, AVE-0005, goserelin acetate, leuprolide acetate, triptorelin pamoate, medroxyprogesterone acetate, hydroxyprogesterone caproate, megestrol acetate, raloxifene, bicalutamide, flutamide, nilutamide, megestrol acetate, CP-724714; TAK-165, HKI- 272, erlotinib, lapatanib, canertinib, ABX-EGF antibody, erbitux, EKB-569, PKI-166, GW- 572016, Ionafarnib, BMS-214662, tipifarnib, amifostine, NVP-LAQ824, suberoyl analide hydroxamic acid, valproic acid, trichostatin A, FK-228, SU11248, sorafenib, KRN951, aminoglutethimide, arnsacrine, anagrelide, L-asparaginase, Bacillus Calmette-Guerin (BCG) vaccine, adriamycin, bleomycin, buserelin, busulfan, carboplatin, carmustine, chlorambucil, cisplatin, cladribine, clodronate, cyproterone, cytarabine, dacarbazine, dactinomycin, daunorubicin, diethylstilbestrol, epirubicin, fludarabine, fludrocortisone, fluoxymesterone, flutamide, gleevec, gemcitabine, hydroxyurea, idarubicin, ifosfamide, imatinib, leuprolide, levamisole, lomustine, mechlorethamine, melphalan, 6-mercaptopurine, mesna, methotrexate, mitomycin, mitotane, mitoxantrone, nilutamide, octreotide, oxaliplatin, pamidronate, pentostatin, plicamycin, porfimer, procarbazine, raltitrexed, rituximab, streptozocin, teniposide, testosterone, thalidomide, thioguanine, thiotepa, tretinoin, vindesine, 13-cis-retinoic acid, phenylalanine mustard, uracil mustard, estramustine, altretamine, floxuridine, S5-deooxyuridine, cytosine arabinoside, 6-mecaptopurine, deoxycoformycin, calcitriol, valrubicin, mithramycin, vinblastine, vinorelbine, topotecan, razoxin, marimastat, COL-3, neovastat, BMS-275291, squalamine, endostatin, SU5416, SU6668, EMDI121974, interleukin-12, IM862, angiostatin, vitaxin, droloxifene, idoxyfene, spironolactone, finasteride, cimitidine, trastuzumab, denileukin diftitox, gefitinib, bortezomib, paclitaxel, cremophor-free paclitaxel, docetaxel, epithilone B, BMS-247550, BMS-310705, droloxifene, 4-hydroxytamoxifen, pipendoxifene, ERA-923, arzoxifene, fulvestrant, acolbifene, lasofoxifene, idoxifene, TSE-424, HMR-3339, ZK186619, topotecan, PTK787 / ZK 222584, VX-745, PD 184352, rapamycin, 40-O-(2-hydroxyethyl)-rapamycin, temsirolimus, AP- 23573, RAD001, ABT-578, BC-210, LY294002, LY292223, LY292696, LY293684, LY293646, wortmannin, ZM336372, L-779,450, PEG-filgrastim, darbepoetin, erythropoietin, granulocyte colony-stimulating factor, zolendronate, prednisone, cetuximab, granulocyte macrophage colony- stimulating factor, histrelin, pegylated interferon alfa-2a, interferon alfa-2a, pegylated interferon alfa-2b, interferon alfa-2b, azacitidine, PEG-L-asparaginase, lenalidomide, gemtuzumab, hydrocortisone, interleukin-11, dexrazoxane, alemtuzumab, all-transretinoic acid, ketoconazole, interleukin-2, megestrol, immune globulin, nitrogen mustard, methylprednisolone, ibritgumomab tiuxetan, androgens, decitabine, hexamethylmelamine, bexarotene, tositumomab, arsenic trioxide, cortisone, editronate, mitotane, cyclosporine, liposomal daunorubicin, Edwina-asparaginase, strontium 89, casopitant, netupitant, an NK-1 receptor antagonist, palonosetron, aprepitant, diphenhydramine, hydroxyzine, metoclopramide, lorazepam, alprazolam, haloperidol, droperidol, dronabinol, dexamethasone, methylprednisolone, prochlorperazine, granisetron, ondansetron, dolasetron, tropisetron, pegfilgrastim, erythropoietin, epoetin alfa, darbepoetin alfa and mixtures thereof. In certain embodiments, the bioactive agent is selected from, but are not limited to, Imatinib mesylate (Gleevac®), Dasatinib (Sprycel®), Nilotinib (Tasigna®), Bosutinib (Bosulif®), Trastuzumab (Herceptin®), trastuzumab-DMI1, Pertuzumab (PerjetaTM), Lapatinib (Tykerb®), Gefitinib (Iressa®), Erlotinib (Tarceva®), Cetuximab (Erbitux®), Panitumumab (Vectibix®), Vandetanib (Caprelsa®), Vemurafenib (Zelboraf®), Vorinostat (Zolinza®), Romidepsin (Istodax®), Bexarotene (Tagretin®), Alitretinoin (Panretin®), Tretinoin (Vesanoid®), Carfilizomib (KyprolisTM), Pralatrexate (Folotyn®), Bevacizumab (Avastin®), Ziv-aflibercept (Zaltrap®), Sorafenib (Nexavar®), Sunitinib (Sutent®), Pazopanib (Votrient®), Regorafenib (Stivarga®), and Cabozantinib (CometrigTM). In certain aspects, the bioactive agent is an anti-inflammatory agent, a chemotherapeutic agent, a radiotherapeutic, an additional therapeutic agent, or an immunosuppressive agent. Suitable chemotherapeutic bioactive agents include, but are not limited to, a radioactive molecule, a toxin, also referred to as cytotoxin or cytotoxic agent, which includes any agent that is detrimental to the viability of cells, and liposomes or other vesicles containing chemotherapeutic compounds. General anti-cancer pharmaceutical agents include: Vincristine (Oncovin®) or liposomal vincristine (Marqibo®), Daunorubicin (daunomycin or Cerubidine®) or doxorubicin (Adriamycin®), Cytarabine (cytosine arabinoside, ara-C, or Cytosar®), L-asparaginase (Elspar®) or PEG-L-asparaginase (pegaspargase or Oncaspar®), Etoposide (VP-16), Teniposide (Vumon®), 6-mercaptopurine (6-MP or Purinethol®), Methotrexate, Cyclophosphamide (Cytoxan®), Prednisone, Dexamethasone (Decadron), imatinib (Gleevec®), dasatinib (Sprycel®), nilotinib (Tasigna®), bosutinib (Bosulif®), and ponatinib (Iclusig™). Examples of additional suitable chemotherapeutic agents include but are not limited to 1-dehydrotestosterone, 5-fluorouracil decarbazine, 6-mercaptopurine, 6-thioguanine, actinomycin D, adriamycin, aldesleukin, an alkylating agent, allopurinol sodium, altretamine, amifostine, anastrozole, anthramycin (AMC)), an anti-mitotic agent, cis-dichlorodiamine platinum (II) (DDP) cisplatin), diamino dichloro platinum, anthracycline, an antibiotic, an antimetabolite, asparaginase, BCG live (intravesical), betamethasone sodium phosphate and betamethasone acetate, bicalutamide, bleomycin sulfate, busulfan, calcium leucouorin, calicheamicin, capecitabine, carboplatin, lomustine (CCNU), carmustine (BSNU), Chlorambucil, Cisplatin, Cladribine, Colchicin, conjugated estrogens, Cyclophosphamide, Cyclothosphamide, Cytarabine, Cytarabine, cytochalasin B, Cytoxan, Dacarbazine, Dactinomycin, dactinomycin (formerly actinomycin), daunirubicin HCL, daunorucbicin citrate, denileukin diftitox, Dexrazoxane, Dibromomannitol, dihydroxy anthracin dione, Docetaxel, dolasetron mesylate, doxorubicin HCL, dronabinol, E. coli L-asparaginase, emetine, epoetin-o, Erwinia L-asparaginase, esterified estrogens, estradiol, estramustine phosphate sodium, ethidium bromide, ethinyl estradiol, etidronate, etoposide citrororum factor, etoposide phosphate, filgrastim, floxuridine, fluconazole, fludarabine phosphate, fluorouracil, flutamide, folinic acid, gemcitabine HCL, glucocorticoids, goserelin acetate, gramicidin D, granisetron HCL, hydroxyurea, idarubicin HCL, ifosfamide, interferon a-2b, irinotecan HCL, letrozole, leucovorin calcium, leuprolide acetate, levamisole HCL, lidocaine, lomustine, maytansinoid, mechlorethamine HCL, medroxyprogesterone acetate, megestrol acetate, melphalan HCL, mercaptipurine, mesna, methotrexate, methyltestosterone, mithramycin, mitomycin C, mitotane, mitoxantrone, nilutamide, octreotide acetate, ondansetron HCL, paclitaxel, pamidronate disodium, pentostatin, pilocarpine HCL, plimycin, polifeprosan 20 with carmustine implant, porfimer sodium, procaine, procarbazine HCL, propranolol, rituximab, sargramostim, streptozotocin, tamoxifen, taxol, teniposide, tenoposide, testolactone, tetracaine, thioepa chlorambucil, thioguanine, thiotepa, topotecan HCL, toremifene citrate, trastuzumab, tretinoin, valrubicin, vinblastine sulfate, vincristine sulfate, and vinorelbine tartrate. In some embodiments, the compound of the present invention is administered in combination with a chemotherapeutic agent (e.g., a cytotoxic agent or another chemical compound useful in the treatment of cancer). Examples of chemotherapeutic agents include alkylating agents, antimetabolites, folic acid analogs, pyrimidine analogs, purine analogs and related inhibitors, vinca alkaloids, epipodopyyllotoxins, antibiotics, L-Asparaginase, topoisomerase inhibitors, interferons, platinum coordination complexes, anthracenedione substituted urea, methyl hydrazine derivatives, adrenocortical suppressant, adrenocorticosteroides, progestins, estrogens, antiestrogen, androgens, antiandrogen, and gonadotropin-releasing hormone analog. Also included is 5-fluorouracil (5-FU), leucovorin (LV), irenotecan, oxaliplatin, capecitabine, paclitaxel, and doxetaxel. Non-limiting examples of chemotherapeutic agents include alkylating agents such as thiotepa and cyclosphosphamide; alkyl sulfonates such as busulfan, improsulfan and piposulfan; aziridines such as benzodopa, carboquone, meturedopa, and uredopa; ethylenimines and methylamelamines including altretamine, triethylenemelamine, trietylenephosphoramide, triethiylenethiophosphoramide and trimethylolomelamine; acetogenins (especially bullatacin and bullatacinone); a camptothecin (including the synthetic analogue topotecan); bryostatin; callystatin; CC-1065 (including its adozelesin, carzelesin and bizelesin synthetic analogues); cryptophycins (particularly cryptophycin 1 and cryptophycin 8), dolastatin; duocarmycin (including the synthetic analogues, KW-2189 and CB1-TMI1 ); eleutherobin; pancratistatin; a sarcodictyin, spongistatin; nitrogen mustards such as chlorambucil, chlornaphazine, cholophosphamide, estramustine, ifosfamide, mechlorethamine, mechlorethamine oxide hydrochloride, melphalan, novembichin, phenesterine, prednimustine, trofosfamide, uracil mustard; nitrosureas such as carmustine, chlorozotocin, fotemustine, lomustine, nimustine, and ranimnustine; antibiotics such as the enediyne antibiotics (e.g. calicheamicin, especially calicheamicin gammall and calicheamicin omegall (see, e.g., Agnew, Chem. Inti. Ed Engl. 33:183- 186 (1994)); dynemicin, including dynemicin A; bisphosphonates, such as clodronate; an esperamicin; as well as neocarzinostatin chromophore and related chromoprotein enediyne antiobiotic chromophores), aclacinomysins, actinomycin, authramycin, azaserine, bleomycins, cactinomycin, carabicin, caminomycin, carzinophilin, chromomycinis, dactinomycin, daunorubicin, detorubicin, 6-diazo- 5-oxo-L-norleucine, ADRIAMYCIN® (doxorubicin, including morpholino-doxorubicin, cyanomorpholino- doxorubicin, 2-pyrrolino-doxorubicin and deoxydoxorubicin), epirubicin, esorubicin, idarubicin, marcellomycin, mitomycins such as mitomycin C, mycophenolic acid, nogalamycin, olivomycins, peplomycin, potfiromycin, puromycin, quelamycin, rodorubicin, streptonigrin, streptozocin, tubercidin, ubenimex, zinostatin, zorubicin; anti-metabolites such as methotrexate and 5-fluorouracil (5- FU); folic acid analogues such as denopterin, methotrexate, pteropterin, trimetrexate; purine analogs such as fludarabine, 6- mercaptopurine, thiamiprine, thioguanine; pyrimidine analogs such as ancitabine, azacitidine, 6- azauridine, carmofur, cytarabine, dideoxyuridine, doxifluridine, enocitabine, floxuridine; androgens such as calusterone, dromostanolone propionate, epitiostanol, mepitiostane, testolactone; anti-adrenals such as aminoglutethimide, mitotane, trilostane; folic acid replenisher such as frolinic acid; aceglatone; aldophosphamide glycoside; aminolevulinic acid; eniluracil; amsacrine; bestrabucil; bisantrene; edatraxate; defofamine; demecolcine; diaziquone; elfomithine; elliptinium acetate; an epothilone; etoglucid; gallium nitrate; hydroxyurea; lentinan; lonidainine; maytansinoids such as maytansine and ansamitocins; mitoguazone; mitoxantrone; mopidanmol; nitraerine; pentostatin; phenamet; pirarubicin; losoxantrone; podophyllinic acid; 2-ethylhydrazide; procarbazine; PSK® polysaccharide complex (JHS Natural Products, Eugene, OR); razoxane; rhizoxin; sizofuran; spirogermanium; tenuazonic acid; triaziquone; 2,2',2"-trichlorotriethylamine; trichothecenes (especially T- 2 toxin, verracurin A, roridin A and anguidine); urethan; vindesine; dacarbazine; mannomustine; mitobronitol; mitolactol; pipobroman; gacytosine; arabinoside ("Ara- C"); cyclophosphamide; thiotepa; taxoids, e.g, TAXOL® (paclitaxel; Bristol-Myers Squibb Oncology, Princeton, NJ), ABRAXANE®, cremophor-free, albumin-engineered nanoparticle formulation of paclitaxel (American Pharmaceutical Partners, Schaumberg, IL), and TAXOTERE® doxetaxel (Rhone-Poulenc Rorer, Antony, France); chloranbucil; GEMZAR® gemcitabine; 6-thioguanine; mercaptopurine; methotrexate; platinum coordination complexes such as cisplatin, oxaliplatin and carboplatin, vinblastine; platinum; etoposide (VP-16), ifosfamide; mitoxantrone; vincristine; NAVELBINE® vinorelbine; novantrone; teniposide; edatrexate; daunomycin, aminopterin; xeloda, ibandronate; irinotecan (e.g, CPT-1 ); topoisomerase inhibitor RFS 2000; difluoromethylomithine (DMFOQ), retinoids such as retinoic acid; capecitabine; and pharmaceutically acceptable salts, acids or derivatives of any of the above. Two or more chemotherapeutic agents can be used in a cocktail to be administered in combination with the compound of the present invention. Suitable dosing regimens of combination chemotherapies are known in the ar. For example, combination dosing regimens are described in Saltz et al., Proc. Am. Soc. Clin. Oncol. 18:233a (1999) and Douillard et al., Lancet 355(9209): 1041 -1047 (2000). Additional therapeutic agents that can be administered in combination with a compound disclosed herein can include bevacizumab, sutinib, sorafenib, 2-methoxyestradiol or 2ME2, finasunate, vatalanib, vandetanib, aflibercept, volociximab, etaracizumab (MEDI-522), cilengitide, erlotinib, cetuximab, panitumumab, gefitinib, trastuzumab, dovitinib, figitumumab, atacicept, rituximab, alemtuzumab, aldesleukine, atlizumab, tocilizumab, temsirolimus, everolimus, lucatumumab, dacetuzumab, HLLI, huN901-DM1, atiprimod, natalizumab, bortezomib, carfilzomib, marizomib, tanespimycin, saquinavir mesylate, ritonavir, nelfinavir mesylate, indinavir sulfate, belinostat, panobinostat, mapatumumab, lexatumumab, dulanermin, ABT-737, oblimersen, plitidepsin, talmapimod, P276-00, enzastaurin, tipifarnib, perifosine, imatinib, dasatinib, lenalidomide, thalidomide, simvastatin, celecoxib, bazedoxifene, AZD4547, rilotumumab, oxaliplatin (Eloxatin), PD0332991, ribociclib (LEE011), amebaciclib (LY2835219), HDM201, fulvestrant (Faslodex), exemestane (Aromasin), PIM447, ruxolitinib (INC424), BGJ398, necitumumab, pemetrexed (Alimta), and ramucirumab (IMC-1121B). In certain embodiments, the additional therapy is a monoclonal antibody (MAb). Some MAbs stimulate an immune response that destroys cancer cells. Similar to the antibodies produced naturally by B cells, these MAbs may “coat” the cancer cell surface, triggering its destruction by the immune system. For example, bevacizumab targets vascular endothelial growth factor (VEGF), a protein secreted by tumor cells and other cells in the tumor’s microenvironment that promotes the development of tumor blood vessels. When bound to bevacizumab, VEGF cannot interact with its cellular receptor, preventing the signaling that leads to the growth of new blood vessels. Similarly, cetuximab and panitumumab target the epidermal growth factor receptor (EGFR), and trastuzumab targets the human epidermal growth factor receptor 2 (HER-2). MAbs that bind to cell surface growth factor receptors prevent the targeted receptors from sending their normal growth-promoting signals. They may also trigger apoptosis and activate the immune system to destroy tumor cells. In one aspect of the present invention, the bioactive agent is an immunosuppressive agent. The immunosuppressive agent can be a calcineurin inhibitor, e.g. a cyclosporin or an ascomycin, e.g. Cyclosporin A (NEORAL®), FK506 (tacrolimus), pimecrolimus, a mTOR inhibitor, e.g. rapamycin or a derivative thereof, e.g. Sirolimus (RAPAMUNE®), Everolimus (Certican®), temsirolimus, zotarolimus, biolimus-7, biolimus-9, a rapalog, e.g.ridaforolimus, azathioprine, campath 1H, a S1P receptor modulator, e.g. fingolimod or an analogue thereof, an anti IL-8 antibody, mycophenolic acid or a salt thereof, e.g. sodium salt, or a prodrug thereof, e.g. Mycophenolate Mofetil (CELLCEPT®), OKT3 (ORTHOCLONE OKT3®), Prednisone, ATGAM®, THYMOGLOBULIN®, Brequinar Sodium, OKT4, T10B9.A-3A, 33B3.1, 15- deoxyspergualin, tresperimus, Leflunomide ARAVA®, CTLAI-Ig, anti-CD25, anti-IL2R, Basiliximab (SIMULECT®), Daclizumab (ZENAPAX®), mizorbine, methotrexate, dexamethasone, ISAtx-247, SDZ ASM 981 (pimecrolimus, Elidel®), CTLA4lg (Abatacept), belatacept, LFA3lg,, etanercept (sold as Enbrel® by Immunex), adalimumab (Humira®), infliximab (Remicade®), an anti-LFA-1 antibody, natalizumab (Antegren®), Enlimomab, gavilimomab, antithymocyte immunoglobulin, siplizumab, Alefacept efalizumab, pentasa, mesalazine, asacol, codeine phosphate, benorylate, fenbufen, naprosyn, diclofenac, etodolac and indomethacin, aspirin and ibuprofen. In some embodiments, the bioactive agent is a therapeutic agent which is a biologic such a cytokine (e.g., interferon or an interleukin (e.g., IL-2)) used in cancer treatment. In some embodiments the biologic is an anti-angiogenic agent, such as an anti-VEGF agent, e.g. bevacizumab (AVASTIN®). In some embodiments the biologic is an immunoglobulin-based biologic, e.g., a monoclonal antibody (e.g., a humanized antibody, a fully human antibody, an Fc fusion protein or a functional fragment thereof) that agonizes a target to stimulate an anti-cancer response, or antagonizes an antigen important for cancer. Such agents include RITUXAN® (rituximab); ZENAPAX® (daclizumab), SIMULECT® (basiliximab), SYNAGIS® (palivizumab); REMICADE® (infliximab); HERCEPTIN® (trastuzumab); MYLOTARG® (gemtuzumab ozogamicin); CAMPATH® (alemtuzumab); ZEVALIN® (ibritumomab tiuxetan); HUMIRA® (adalimumab); XOLAIR® (omalizumab); BEXXAR® (tositumomab-1- 131 ); RAPTIVA® (efalizumab); ERBITUX® (cetuximab); AVASTIN® (bevacizumab); TYSABRI® (natalizumab); ACTEMRA® (tocilizumab); VECTIBIX® (panitumumab); LUCENTIS® (ranibizumab); SOURIS® (eculizumab); CIMZIA® (certolizumab pegol); SIMPONI® (golimumab); ILARIS® (canakinumab); STELARA® (ustekinumab); ARZERRA® (ofatumumab); PROLIA® (denosumab); NUMAX® (motavizumab), ABTHRAX® (raxibacumab); BENLYSTA® (belimumab), YERVOY® (ipilimumab); ADCETRIS® (brentuximab vedotin); PERJETA® (pertuzumab); KADCYLA® (ado- trastuzumab emtansine); and GAZYVA® (obinutuzumab). Also included are antibody-drug conjugates. In certain embodiments, the additional therapy is bendamustine. In certain embodiments, the additional therapy is obinutuzmab. In certain embodiments, the additional therapy is a proteasome inhibitor, for example ixazomib or oprozomib. In certain embodiments, the additional therapy is a histone deacetylase inhibitor, for example ACY241. In certain embodiments, the additional therapy is a BET inhibitor, for example GSK525762A, OTX015, BMS-986158, TEN- 010, CPI-0610, INCB54329, BAY1238097, FT-1101, ABBV-075, BI 894999, GS-5829, GSK1210151A (I-BET-151), CPI-203, RVX-208, XD46, MS436, PFI-1, RVX2135, ZEN3365, XD14, ARV-771, MZ-1, PLX5117, 4-[2-(cyclopropylmethoxy)-5-(methanesulfonyl)phenyl]-2- methylisoquinolin-1(2H)-one, EP11313 and EP11336. In certain embodiments, the additional therapy is an MCL-1 inhibitor, for example AZD5991, AMG176, MIK665, S64315, or S63845. In certain embodiments, the additional therapy is an LSD-1 inhibitor, for example ORY-1001, ORY-2001, INCB-59872, IMG-7289, TAK-418, GSK-2879552, 4-[2-(4-amino-piperidin-1-yl)-5- (3-fluoro-4-methoxy-phenyl)-1-methyl-6-oxo-1,6-dihydropyrimidin-4-yl]-2-fluoro-benzonitrile or a salt thereof. In certain embodiments, the additional therapy is a CS1 antibody, for example elotuzumab. In certain embodiments, the additional therapy is a CD38 antibody, for example daratumumab or isatuximab. In certain embodiments, the additional therapy is a BCMA antibody or antibody-conjugate, for example GSK2857916 or BI 836909. In certain embodiments, the bioactive agent is selinexor. In certain embodiments, Compound 1 is administered in combination with selinexor, In certain embodiments, Compound 1 is administered in combination with aspirin, In certain embodiments, Compound 2, Compound 3, Compound 4, Compound 5, Compound 6, Compound 7, Compound 8, Compound 9, Compound 10, Compound 11, Compound 12, or Compound 13 is administered in combination with selinexor. In certain embodiments, Compound 2, Compound 3, Compound 4, Compound 5, Compound 6, Compound 7, Compound 8, Compound 9, Compound 10, Compound 11, Compound 12, or Compound 13 is administered in combination with aspirin. In other embodiments a compound described herein is administered in combination with a drug selected from selinexor, oxaphenamide, belantamab mafodotin, denosumab, zoledronic acid, plerixafor, eltrombopag, ipilumumab, palbociclib, ricolinostat, afuresertib, dinaciclib, filanesib, indatuximab ravtansine, masitinib, sonidegib, sotatercept, ulocuplumab, and urelumab. In certain embodiments Compound 1 is used in combination with a chemokine receptor antagonist, for example plerixafor. In certain embodiments Compound 1 is used in combination with a vaccine,...

Claims

CLAIMS We claim:

1. A method of treating a disorder mediated by Ikaros and / or Aiolos comprising administering a dose of no more than about 500 micrograms (ug) once a day (QD) or twice a day (BID) of a compound selected from =0 (Compound 1) 6) oro 0 =0 A NH J (Compound 2) O w CO AI IT 4 oO ra =0 4 J—NH Oo (Compound 3) ora @ g 0 J : d=0 NH J Cc NC E 0 O- OX Yd “F (Compound 4) =0 NH J NL ! y v on’ SA (Compound 5) oO (0 20S o =o & NH oO (Compound 6) 0 x N— » N= on d \— 0 =o A J—NH oO (Compound 7) 0 yin " 0 =o A J—NH 0 (Compound 8) 0 XN 5 | N— LO = J 0 =0 bh J—NH 0 (Compound 9) Oo Kin "d 0 =0 i J—NH OQ (Compound 10) AY Oo w CO NYA g & Nt 9 con (Compound 12) o oo (Compound 11) Q (= eo N NH A 0 (Compound 12) F 0 J N— =O NH a (Compound 13) or a pharmaceutically acceptable salt thereof. 0 CLO KOT ¢ rmaceutically acceptable salt thereof.

2. The method of claim 1, wherein the compound is administered at a dose between about 500 micrograms and 1 microgram.

3. The method of claim 1 or claim 2, wherein the compound is administered for multiple days with a drug holiday in between subsequent treatment cycles.

4. The method of claim 3, wherein the compound is administered once or twice a day for at least 13, 14 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26 or 27 continuous days, and then the drug holiday is taken until the next 28-day cycle.

5. The method of claim 3, wherein the compound is administered once or twice a day for 21 days followed by a 7-day holiday.

6. The method of any one of claims 1-5, wherein the dose is less than or equal to about 400 Ug.

7. The method of any one of claims 1-5, wherein the dose is less than or equal to about 300 Ug.

8. The method of any one of claims 1-5, wherein the dose is less than or equal to about 200 Ug.

9. The method of any one of claims 1-5, wherein the dose is less than or equal to about 100 Ug.

10. The method of any one of claims 1-5, wherein the dose is less than or equal to about 50 pug.

11. The method of any one of claims 1-5, wherein the dose is less than or equal to about 25 UE.

12. The method of any one of claims 1-5, wherein the dose is less than or equal to about 10 pug.

13. The method of any one of claims 1-5, wherein the dose is less than or equal to about 5 ug.

14. The method of any one of claims 1-5, wherein the dose is about 50 ug.

15. The method of any one of claims 1-5, wherein the dose is about 25 ug.

16. The method of any one of claims 1-5, wherein the dose is about 10 pug.

17. The method of any one of claims 1-5, wherein the dose is about 5 ug.

18. The method of any one of claims 1-17, wherein the disorder is a diffuse large B-cell lymphoma.

19. The method of claim 18, wherein the diffuse large B-cell lymphoma is an activated B-cell lymphoma.

20. The method of claim 18, wherein the diffuse large B-cell lymphoma is a germinal center B-cell lymphoma.

21. The method of any one of claims 1-17, wherein the disorder is an anaplastic large cell lymphoma.

22. The method of any one of claims 1-17, wherein the disorder is a cutaneous T-cell lymphoma.

23. The method of any one of claims 1-17, wherein the disorder is mantle cell lymphoma.

24. The method of any one of claims 1-17, wherein the disorder is multiple myeloma.

25. The method of any one of claims 1-24, wherein the disorder is resistant to treatment with first generation IMiD drugs.

26. The method of claim 25, wherein the disorder is resistant to treatment with thalidomide.

27. The method of claim 25, wherein the disorder is resistant to treatment with pomalidomide.

28. The method of claim 25, wherein the disorder is resistant to treatment with lenalidomide.

29. The method of claim 25, wherein the disorder is resistant to treatment with iberdomide.

30. A method of treating a disorder mediated by Ikaros (IKZF1) and / or Aiolos (IKZF3) wherein a blood or tissue sample is taken from a patient and the concentration of one or more biomarkers selected from IRF-1, caspase-3, IL-2, and IFN-y, is determined, wherein if the patient has a statistically lower concentration of the biomarker(s) than a healthy person then a compound selected from Compound 1, Compound 2, Compound 3, Compound 4, Compound 5, Compound 6, Compound 7, Compound 8, Compound 9, Compound 10, Compound 11, Compound 12, and Compound 13, or a pharmaceutically acceptable salt thereof is administered to the patient.

31. The method of claim 30, wherein the statistically lower concentration of the biomarker(s) is 5% lower than an average healthy patient.

32. The method of claim 30, wherein the statistically lower concentration of the biomarker(s) is 20% lower than an average healthy patient.

33. A method of treating a disorder mediated by Ikaros (IKZF1) and / or Aiolos (IKZF3) wherein a blood or tissue sample is taken from a patient and the concentration of one or more biomarkers selected from cyclin D1, E2F1, ZFP91, SALL4, IRF-4, BLIMP1, and MYC is determined, wherein if the patient has a statistically higher concentration of the biomarker(s) than a healthy person then a compound selected Compound 1, Compound 2, Compound 3, Compound 4, Compound 5, Compound 6, Compound 7, Compound 8, Compound 9, Compound 10, Compound 11, Compound 12, and Compound 13, or a pharmaceutically acceptable salt thereof is administered to the patient.

34. The method of claim 33, wherein the statistically higher concentration of the biomarker(s) is 5% higher than an average healthy patient.

35. The method of claim 33, wherein the statistically higher concentration of the biomarker(s) is 20% higher than an average healthy patient.

36. A method of treating a disorder mediated by Ikaros (IKZF1) and / or Aiolos (IKZF3) wherein a patient is administered a compound selected from Compound 1, Compound 2, Compound 3, Compound 4, Compound 5, Compound 6, Compound 7, Compound 8, Compound 9, Compound 10, Compound 11, Compound 12, and Compound 13, or a pharmaceutically acceptable salt thereof, and then a blood or tissue sample is taken from the patient and the concentration of one or more biomarkers selected from IRF-1, caspase- 3, IL-2, and IFN-y, is determined, wherein if the concentration of the biomarker(s) is not significantly increased, then the dose of the compound is increased.

37. The method of claim 36, wherein the dose of the compound is increased if the concentration of the biomarkers(s) is not increased by at least about 25%.

38. The method of claim 36, wherein the dose of the compound is increased if the concentration of the biomarkers(s) is not increased by at least about 100%, 39. The method of claim 36, wherein the dose of the compound is increased if the concentration of the biomarkers(s) is not increased by at least about 200%.

40. A method of treating a disorder mediated by Ikaros (IKZF1) and / or Aiolos (IKZF3) wherein a patient is administered a compound selected from Compound 1, Compound 2, Compound 3, Compound 4, Compound 5, Compound 6, Compound 7, Compound 8, Compound 9, Compound 10, Compound 11, Compound 12, and Compound 13, or a pharmaceutically acceptable salt thereof, and then a blood or tissue sample is taken from the patient and the concentration of one or more biomarkers selected from cyclin D1, E2F1, ZFP91, SALL4, IRF-4, BLIMP1, and MYC is determined, wherein if the concentration of the biomarker(s) is not significantly decreased, then the dose of the compound is increased.

41. The method of claim 40, wherein the dose of the compound is increased if the concentration of the biomarkers(s) is not decreased by at least about 10%.

42. The method of claim 40, wherein the dose of the compound is increased if the concentration of the biomarkers(s) is not decreased by at least about 25%.

43. The method of claim 40, wherein the dose of the compound is increased if the concentration of the biomarkers(s) is not decreased by at least about 50%.

44. A method of treating a disorder mediated by Ikaros and / or Aiolos comprising administering an effective amount of a compound selected from Compound 1, Compound 2, Compound 3, Compound 4, Compound 5, Compound 6, Compound 7, Compound 8, Compound 9, Compound 10, Compound 11, Compound 12, and Compound 13 or a pharmaceutically acceptable salt thereof, to a patient in need thereof, wherein the Ikaros or Aiolos mediated disorder is an activated diffuse large B-cell lymphoma or germinal center large B-cell lymphoma.

45. A method of treating a disorder mediated by Ikaros and / or Aiolos comprising administering an effective amount of a compound selected from Compound 1, Compound 2, Compound 3, Compound 4, Compound 5, Compound 6, Compound 7, Compound 8, Compound 9, Compound 10, Compound 11, Compound 12, and Compound 13, or a pharmaceutically acceptable salt thereof, wherein the patient also receives a BTK inhibitor selected from acalabrutinib, spebrutinib, zanubrutinib, LOX0-305, evobrutinib, TG-1701, tolebrutinib, BIIB091, DZD-9008, HZ-A-018, orelabrutinib, ACO0S8TA, SN1011, nilzabrutinib, ARQ 531, DTRMWXHS-12, INJ-64264681, branebrutinib, and fenebrutinib.

46. A method of treating a disorder mediated by Ikaros and / or Aiolos comprising administering an effective amount of a compound selected from Compound 1, Compound 2, Compound 3, Compound 4, Compound 5, Compound 6, Compound 7, Compound 8, Compound 9, Compound 10, Compound 11, Compound 12, and Compound 13 or a pharmaceutically acceptable salt thereof, wherein the patient also receives a CD38 antibody selected from felzartamab, GBR 1342, TAK-573, CID-103, OKT10, STI-6129, SGX301, TAK-079, and mezagitamab.

47. A method of treating a disorder mediated by Ikaros and / or Aiolos comprising administering an effective amount of a compound selected from Compound 1, Compound 2, Compound 3, Compound 4, Compound 5, Compound 6, Compound 7, Compound 8, Compound 9, Compound 10, Compound 11, Compound 12, and Compound 13 or a pharmaceutically acceptable salt thereof, wherein the patient also receives a proteasome inhibitor selected from ixazomib citrate, oprozomib, delanzomib, lactacystin, epoxomicin, MG132, MG-262, CEP-18770, NEOSH 101, TQB3602, and KZR-616.

48. A method of treating a disorder mediated by Ikaros and / or Aiolos comprising administering an effective amount of a compound selected from Compound 1, Compound 2, Compound 3, Compound 4, Compound 5, Compound 6, Compound 7, Compound 8, Compound 9, Compound 10, Compound 11, Compound 12, and Compound 13 or a pharmaceutically acceptable salt thereof, to a patient in need thereof, wherein the patient also receives an IMiD selected from CC-92480, CC-90009, and CC-99282.

49. A method of treating a disorder mediated by Ikaros and / or Aiolos comprising administering an effective amount of a compound selected from Compound 1, Compound 2, Compound 3, Compound 4, Compound 5, Compound 6, Compound 7, Compound 8, Compound 9, Compound 10, Compound 11, Compound 12, and Compound 13 or a pharmaceutically acceptable salt thereof, to a patient in need thereof, wherein the patient also receives a HDAC inhibitor selected from trapoxin B, sodium phenylbutyrate, tacedinaline, mocetinostat, BRD73954, BG45, domatinostat, cay 10603, HPOB, TMP269, nexturastat A, Santacruzamate A, splitomicin, LMK-235, sodium butyrate, pivaloyloxymethyl butyrate, pyroxamide, abexinostat, resminostat, givinostat, quisinostat, Psammaplin A, KD5170, 1- Alaninechlamydocin, depudecin, and CUDC-101, 50. A method of treating a disorder mediated by Ikaros and / or Aiolos comprising administering an effective amount of a compound selected from Compound 1, Compound 2, Compound 3, Compound 4, Compound 5, Compound 6, Compound 7, Compound 8, Compound 9, Compound 10, Compound 11, Compound 12, and Compound 13 or a pharmaceutically acceptable salt thereof, to a patient in need thereof, wherein the patient also receives a compound selected from selinexor, oxaphenamide, belantamab mafodotin, denosumab, zoledronic acid, plerixafor, eltrombopag, ipilumumab, palbociclib, ricolinostat, afuresertib, dinaciclib, filanesib, indatuximab ravtansine, masitinib, sonidegib, sotatercept, ulocuplumab, and urelumab.

51. The method of any one of claims 1-50, wherein the compound is =0 (Compound 1) ) o 0) N = 0 = Lo 0 oL_ tically acceptable salt thereof. or a pharmaceutically acceptable salt thereof.

52. The method of any one of claims 1-50, wherein the compound is =o i J—NH oO NT (Compound 2) or a pharmaceutically acceptable salt thereof, Oo ww C= AT ceutically acceptable salt thereof.

53. The method of any one of claims 1-50, wherein the compound is =0 I J—NH Oo NF (Compound 3) or a pharmaceutically acceptable salt thereof, oO Fo 4g p— { N SOs naceutically acceptable salt thereof.

54. The method of any one of claims 1-50, wherein the compound is =0 i J—NH Oo Cc NC E 0 Ay OX Yd “F NC” ~~ °F (Compound 4) or a pharmaceutically acceptable salt thereof.

55. The method of any one of claims 1-50, wherein the compound is =0 A NH J nN ! ! v oO SAN (Compound 5) or a pharmaceutically acceptable salt thereof. oO (CO STAT 4 tically acceptable salt thereof.

56. The method of any one of claims 1-50, wherein the compound is =o NH J o x N— N= 7 NON PB d NN v acceptable salt thereof, o oo (Compound 6) or a pharmaceutically acceptable salt thereof, 57. The method of any one of claims 1-50, wherein the compound is =o A NH a 0 ww C0 XO? eutically acceptable salt thereof. NT - (Compound 7) or a pharmaceutically acceptable salt thereof, 58. The method of any one of claims 1-50, wherein the compound is =o A J—NH oO NNT B (Compound 8) or a pharmaceutically acceptable salt thereof, 0 A x N— Ova 4 eutically acceptable salt thereof.

59. The method of any one of claims 1-50, wherein the compound is =0 fn NH J A) NN 7 B (Compound 9) or a pharmaceutically acceptable salt thereof, o w C0 Oa ¢ y acceptable salt thereof.

60. The method of any one of claims 1-50, wherein the compound is =0 NH J NN TY (Compound 10) or a pharmaceutically acceptable salt thereof. Oo NR ALOE J J ceutically acceptable salt thereof.

61. The method of any one of claims 1-50, wherein the compound is = WE RI MAAR AAR ARIAS oy FRA AAR MI AAR ME 0 N TH N. NH OK _ Se | o 0 aceutically acceptable salt thereof. 0 oo (Compound 11) or a pharmaceutically acceptable salt thereof, 62. The method of any one of claims 1-50, wherein the compound is =0 oro OT Nt (Compound 12) or a pharmaceutically acceptable salt thereof, 63. The method of any one of claims 1-50, wherein the compound is F LJ N— =o dh NH J ry NT B (Compound 13) or a pharmaceutically acceptable salt thereof. Oo vw Clow NN = g J lly acceptable salt thereof.

64. The method of any one of claims 1-63, wherein a Bruton tyrosine kinase inhibitor is also administered to the patient.

65. The method of claim 64, wherein the Bruton tyrosine kinase inhibitor is ibrutinib.

66. The method of any one of claims 1-65, wherein a corticosteroid is also administered to the patient.

67. The method of claim 66, wherein the corticosteroid is dexamethasone.

68. The method of any one of claims 1-67, wherein CAR T-cell therapy is also administered to the patient.

69. The method of any one of claims 1-67, wherein an antibody-drug conjugate is also administered to the patient.

70. The method of any one of claims 1-67, wherein BiTE therapy is also administered to the patient.

71. The method of any one of claims 1-67, wherein a bispecific antibody is also administered to the patient.

72. The method of any one of claims 1-67, wherein a monoclonal antibody is also administered to the patient.

73. The method of any one of claims 1-67, wherein a BTK inhibitor selected from acalabrutinib, spebrutinib, zanubrutinib, LOXO0-308, evobrutinib, TG-1701, tolebrutinib, BIIB091, DZD-9008, HZ-A-018, orelabrutinib, ACO0S8TA, SN1011, rilzabrutinib, ARQ 531, DTRMWXHS-12, INJ-64264681, branebrutinib, ibrutinib, and fenebrutinib is also administered to the patient.

74. The method of any one of claims 1-67, wherein a CD38 antibody selected from felzartamab, daratumumab, GBR 1342, TAK-573, CID-103, OKT10, STI-6129, SGX301, TAK-079, and mezagitamab is also administered to the patient.

75. The method of any one of claims 1-67, wherein a proteasome inhibitor selected from ixazomib citrate, oprozomib, delanzomib, lactacystin, bortezomib, carfilzomib, VLX1570, epoxomicin, MG132, MG-262, CEP-18770, NEQOSH101, TQB3602, and KZR-616 is also administered to the patient.

76. The method of any one of claims 1-67, wherein an IMiD selected from pomalidomide, lenalidomide, thalidomide, iberdomide C(C-92480, CC-90009, and CC-99282 is also administered to the patient.

77. The method of any one of claims 1-67, wherein an HDAC inhibitor selected from trapoxin B, sodium phenylbutyrate, tacedinaline, mocetinostat, BRD73954, BG45, domatinostat, cay10603, HPOB, TMP269, nexturastat A, Santacruzamate A, splitomicin, LMK-235, sodium butyrate, pivaloyloxymethyl butyrate, pyroxamide, abexinostat, resminostat, givinostat, quisinostat, Psammaplin A, KD5170, 1-Alaninechlamydocin, depudecin, and CUDC-101 is also administered to the patient.

78. The method of any one of claims 1-67, wherein a compound selected from selinexor, oxaphenamide, belantamab mafodotin, denosumab, zoledronic acid, plerixafor, eltrombopag, ipilumumab, palbociclib, ricolinostat, aturesertib, dinaciclib, filanesib, indatuximab ravtansine, masitinib, sonidegib, sotatercept, ulocuplumab, and urelumab is also administered to the patient.

79. The method of any one of claims 1-78, wherein the compound selected from Compound 1, Compound 2, Compound 3, Compound 4, Compound 5, Compound 6, Compound 7, Compound 8, Compound 9, Compound 10, Compound 11, Compound 12, and Compound 13, or a pharmaceutically acceptable salt thereof is administered once a day.

80. The method of any one of claims 1-78, wherein the compound selected from Compound 1, Compound 2, Compound 3, Compound 4, Compound 5, Compound 6, Compound 7, Compound 8, Compound 9, Compound 10, Compound 11, Compound 12, and Compound 13, or a pharmaceutically acceptable salt thereof is administered twice a day.

81. The method of any one of claims 1-80, wherein the disorder is Non-Hodgkin's Lymphoma.

82. The method of any one of claims 1-80, wherein the disorder is Multiple Myeloma.

83. The method of any one of claims 1-82, wherein the disorder is relapsed.

84. The method of any one of claims 1-82, wherein the disorder is refractory.

85. The method of any one of claims 1-82, wherein the disorder is relapsed and refractory.

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