Combination Therapy for Cancer

Abstract

The present disclosure provides combination therapies comprising an anti-BCMA antigen binding protein, such as belantamab mafodotin; an immunomodulatory imid drug (IMiD); a proteasome inhibitor; and a corticosteroid. The present disclosure also provides combination therapies for treating newly diagnosed multiple myeloma.

Description

[Technical field]

[0001] Each reference cited in this disclosure is incorporated herein by reference in its entirety.

[0002] The present disclosure relates generally to combination therapies for newly diagnosed multiple myeloma. [Background technology]

[0003] The treatment of newly diagnosed multiple myeloma (NDMM) has changed dramatically over the past two decades from a nearly uniform chemotherapy regimen to an approach based on the patient's performance status and risk. The standard of care for matched multiple myeloma patients is high-dose chemotherapy with autologous stem cell transplantation after completion of induction therapy. However, some patients, especially the elderly, are ineligible for transplantation due to frailty and / or comorbidities. For such patients, treatment with highly active two- or three-drug combination regimens such as lenalidomide (REVLIMID®) / dexamethasone (Rd); daratumumab (DARZALEX®)+Rd; or bortezomib (VELCADE®), lenalidomide (REVLIMID®), and dexamethasone (VRd) is considered.

[0004] The choice of treatment in newly diagnosed MM (NDMM) patients depends largely on the individual's suitability for autologous stem cell transplantation (ASCT). ASCT is usually only suitable for better-fit patients, typically those younger than 65–75 years; therefore, transplant-ineligible (TI) patients constitute the majority of NDMM patients. These patients have a worse clinical prognosis in terms of progression-free survival (PFS), overall survival (OS), or minimal residual disease (MRD) negativity achievement rate compared to patients who can undergo ASCT. Thus, there is an unmet clinical need to improve prognosis through the addition of effective novel therapies to the standard of care (SoC) first-line NDMM backbone agents. Summary of the Invention

[0005] One embodiment of the present disclosure is a combination therapy comprising: (a) an anti-B-cell maturation antigen (BCMA) antigen binding protein, such as belantamab mafodotin; (b) a therapeutically effective amount of a proteasome inhibitor, such as bortezomib; (c) a therapeutically effective amount of an immunomodulatory imide drug, such as lenalidomide; and (d) a therapeutically effective amount of a corticosteroid, such as dexamethasone.

[0006] Another aspect of the disclosure is a method of treating newly diagnosed multiple myeloma comprising administering a therapeutically effective amount of each component of the combination therapy.

[0007] Another aspect of the present disclosure is a kit. In some embodiments, the kit disclosed herein is for use in the treatment of newly diagnosed multiple myeloma. In some embodiments, the kit disclosed herein may comprise a combination disclosed herein and instructions for use in treatment.

[0008] Yet another aspect of the present disclosure is a pre-filled syringe or an automatic injection device. In some embodiments, the pre-filled syringe or automatic injection device disclosed herein may comprise a combination disclosed herein.

[0009] The present disclosure provides combination therapy and its use for treating newly diagnosed multiple myeloma. The present disclosure also provides combination therapy for maintenance treatment of multiple myeloma. "Combination therapy" as used herein means a therapy comprising two or more active agents. These two or more active agents can be administered in separate dosage forms (e.g., the first agent can be a lyophilized powder, the second agent can be an aqueous solution, and the third or subsequent agents can be tablets, capsules, or other oral dosage forms). These two or more active agents can be administered simultaneously or at separate times, and each can be administered by the same route or by different routes (e.g., the first agent can be administered intravenously, the second agent can be administered subcutaneously, and the third or subsequent agents can be administered orally). "Newly diagnosed multiple myeloma" as used herein means multiple myeloma that has not been previously treated with standard of care (SoC) for multiple myeloma.

[0010] In some embodiments, the combination therapy of the present disclosure comprises an anti-BCMA antigen binding protein, such as belantamab mafodotin, and an SoC for newly diagnosed multiple myeloma. In some embodiments, the SoC comprises an immunomodulatory imid drug and a corticosteroid. In some embodiments, the SoC comprises an immunomodulatory imid drug, an anti-CD38 antibody, and a corticosteroid. In some embodiments, the SoC comprises a proteasome inhibitor, an immunomodulatory imid drug, and a corticosteroid. In some embodiments, any of the above combination therapies further comprise a gamma-secretase inhibitor.

[0011] In some embodiments, the combination therapy of the present disclosure comprises an anti-BCMA antigen binding protein, such as belantamab mafodotin, and an SoC for maintenance treatment of multiple myeloma. In some embodiments, the SoC comprises an immunomodulatory imid drug and a corticosteroid. In some embodiments, any of the above combination therapies further comprises a gamma-secretase inhibitor.

[0012] "Q3W" refers to one administration every 3 weeks. "Q4W" refers to one administration every 4 weeks. "Q6W" refers to one administration every 6 weeks. "Q8W" refers to one administration every 8 weeks. "Q10W" refers to one administration every 10 weeks. "Q12W" refers to one administration every 12 weeks.

[0013] "Q3 / 4W" refers to dosing once every 3 weeks for the initial period, followed by dosing once every 4 weeks for the subsequent period. In some embodiments, "Q3 / 4W" refers to dosing once every 3 weeks for 8 cycles, each cycle being 21 days, followed by dosing once every 4 weeks from cycle 9 onwards. "Q6 / 8W" refers to dosing once every 6 weeks for the initial period, followed by dosing once every 8 weeks for the subsequent period. In some embodiments, "Q6 / 8W" refers to dosing once every 6 weeks for 8 cycles, each cycle being 21 days, followed by dosing once every 8 weeks from cycle 9 onwards. "Q9 / 12W" refers to dosing once every 9 weeks for the initial period, followed by dosing once every 12 weeks for the subsequent period. In some embodiments, "Q9 / 12W" refers to dosing once every 9 weeks for 8 cycles, each cycle being 21 days, followed by dosing once every 12 weeks from cycle 9 onwards.

[0014] Components of Combination Therapy Anti-BCMA antigen-binding proteins The term "anti-BCMA antigen binding protein" as used herein refers to antibodies and other protein constructs, such as domains, that are capable of binding to BCMA. The terms "BCMA binding protein" and "BCMA antigen binding protein" are used interchangeably herein. It does not include the natural cognate ligand or receptor.

[0015] The anti-BCMA antigen binding proteins described herein may bind to human BCMA, including for example a human BCMA containing the amino acid sequence of GenBank Accession No. Q02223.2, or a gene encoding a human BCMA having at least 90 percent homology or at least 90% identity thereto.

[0016] Exemplary anti-BCMA antigen binding proteins, and methods of making them, are disclosed in WO 2012 / 163805. Additional exemplary anti-BCMA antigen binding proteins include those disclosed in WO 2016 / 014789, WO 2016 / 090320, WO 2016 / 090327, WO 2016 / 020332, WO 2016 / 079177, WO 2014 / 122143, WO 2014 / 122144, WO 2017 / 021450, WO 2016 / 014565, WO 2014 / 068079, WO 201 and those described in U.S. Patent Application Publication Nos. WO 2015 / 166649, WO 2015 / 158671, WO 2015 / 052536, WO 2014 / 140248, WO 2013 / 072415, WO 2013 / 072406, WO 2014 / 089335, U.S. Patent Application Publication No. 2017 / 165373, WO 2013 / 154760, WO 2018 / 201051, and WO 2017 / 051068.

[0017] In some embodiments, the anti-BCMA antigen binding protein is an anti-BCMA antibody. The term "antibody" is used herein in the broadest sense to refer to a molecule having an immunoglobulin-like domain (e.g., IgG, IgM, IgA, IgD, or IgE), and includes monoclonal antibodies, recombinant antibodies, polyclonal antibodies, chimeric antibodies, human antibodies, humanized antibodies, multispecific antibodies including bispecific antibodies, and heteroconjugate antibodies; single variable domain antibodies (e.g., domain antibodies (DABs)), antigen-binding antibody fragments, Fab, F(ab')2, Fv, disulfide-linked Fvs, single chain Fvs, disulfide-linked scFvs, diabodies, tandem diabodies (TandAbs), and the like, as well as modified versions of any of the above (for a review of alternative "antibody" formats, see Holliger and Hudson, Nature Biotechnology, 2005, Vol 23, No. 9, 1126-1136).

[0018] A complete antibody, whole antibody, or intact antibody, used interchangeably herein, refers to a heterotetrameric glycoprotein with an approximate molecular weight of 150,000 Daltons. An intact antibody is composed of two identical heavy chains (HC) and two identical light chains (LC) linked by covalent disulfide bonds. This H2L2 structure folds to form three functional domains, including two antigen-binding fragments known as the "Fab" fragment and the "Fc" crystallization fragment. The Fab fragment is composed of the amino-terminal variable domains, the variable heavy chain (VH) domain or the variable light chain (VL) domain, and the carboxyl-terminal constant domains, the CH1 (heavy chain) domain and the CL (light chain) domain. The Fc fragment is composed of two domains formed by the dimerization of the paired CH2 and CH3 regions. The Fc can trigger effector functions by binding to receptors on immune cells or by binding to C1q, the first component of the classical complement pathway. The five antibody classes (IgM, IgA, IgG, IgE, and IgD) are defined by distinct heavy chain amino acid sequences called μ, α, γ, ε, and δ, respectively, and each heavy chain can pair with either a K or a λ light chain. The majority of antibodies in serum belong to the IgG class, and there are four human IgG isotypes (IgG1, IgG2, IgG3, and IgG4), whose sequences differ mainly in the hinge region.

[0019] Fully human antibodies can be obtained using a variety of methods, for example, using yeast-based libraries or transgenic animals (e.g., mice) capable of producing a repertoire of human antibodies. Yeast displaying human antibodies on their surface that bind to the antigen of interest can be selected using FACS (fluorescence activated cell sorting)-based methods or by capture on beads with labeled antigen. Transgenic animals modified to express human immunoglobulin genes can be immunized with the antigen of interest and antigen-specific human antibodies can be isolated using B cell sorting techniques. Human antibodies produced using these techniques may then be characterized for desired properties such as affinity, development suitability, and selectivity.

[0020] Alternative antibody formats include alternative scaffolds in which one or more CDRs of the antigen binding protein may be placed onto a suitable non-immunoglobulin protein scaffold or framework, such as an affibody, an SpA scaffold, an LDL receptor class A domain, an avimer (see, e.g., U.S. Patent Application Publication Nos. 2005 / 0053973, 2005 / 0089932, 2005 / 0164301), or an EGF domain.

[0021] "CDR" is defined as the complementarity determining region amino acid sequence of an antigen binding protein. These CDRs are the hypervariable regions of immunoglobulin heavy and light chains. There are three heavy chain CDRs and three light chain CDRs (or CDR regions) in the variable part of an immunoglobulin. That is, "CDRs" as used herein refers to all three heavy chain CDRs, all three light chain CDRs, all heavy and light chain CDRs, or at least two CDRs.

[0022] As used herein, amino acid residues in variable domain sequences and variable domain regions within a full-length antigen-binding sequence, e.g., within an antibody heavy chain sequence or an antibody light chain sequence, are numbered according to the Kabat numbering convention. Similarly, the terms "CDR", "CDRL1", "CDRL2", "CDRL3", "CDRH1", "CDRH2", and "CDRH3" follow the Kabat numbering convention. For further information, see Kabat et al., Sequences of Proteins of Immunological Interest, 4th Ed., US Department of Health and Human Services, National Institutes of Health (1987).

[0023] It is clear to those skilled in the art that there are other numbering conventions for amino acid residues in variable domain sequences and full-length antibody sequences. There are also other numbering conventions for CDR sequences, such as those defined in Chothia et al. (1989) Nature 342: 877-883. Depending on the structure and protein folding of the antigen-binding protein, other residues may be considered as part of the CDR sequence, and it will be understood by those skilled in the art.

[0024] Other numbering conventions for CDR sequences available to those skilled in the art include the "AbM" system (University of Bath) and the "Contact" system (University College London).

[0025] In some embodiments, the anti-BCMA binding protein comprises any one or combination of the following CDRs as shown in the table below. [Table 1]

[0026] The CDRs may be modified by substitution, deletion, or addition of at least one amino acid, and the variant antigen binding protein substantially retains the biological property of the modified protein, such as binding to antigen.

[0027] In some embodiments, the anti-BCMA antigen binding protein comprises a CDRH1 of SEQ ID NO:1, a CDRH2 of SEQ ID NO:2, a CDRH3 of SEQ ID NO:3, a CDRL1 of SEQ ID NO:4, a CDRL2 of SEQ ID NO:5, and a CDRL3 of SEQ ID NO:6.

[0028] In some embodiments, the anti-BCMA antigen binding protein comprises CDR sequences having at least 90% or 95% or 99% sequence identity to CDRH1 of SEQ ID NO: 1, CDRH2 of SEQ ID NO: 2, CDRH3 of SEQ ID NO: 3, CDRL1 of SEQ ID NO: 4, CDRL2 of SEQ ID NO: 5, and / or CDRL3 of SEQ ID NO: 6. "Percent identity" or "% identity" between a query amino acid sequence and a subject amino acid sequence is the value of "identity" expressed as a percentage, calculated over the entire length of the query sequence using an appropriate algorithm (e.g., Needleman-Wunsch or GenePAST / KERR) or software (e.g., DNASTAR® LASERGENE®, or GenePAST / KERR) after pairwise full sequence alignment using an appropriate algorithm (e.g., BLASTP, FASTA, Needleman-Wunsch, Smith-Waterman, LALIGN, or GenePAST / KERR) or software (e.g., DNASTAR® LASERGENE®, GENOMEQUEST®, EMBOSS Needle, or EMBOSS infoalign). Importantly, the query amino acid sequence may be described by an amino acid sequence disclosed herein, in particular in one or more claims.

[0029] A query sequence may be 100% identical to a subject sequence, or may contain up to a certain integer number of amino acid or nucleotide changes when compared to the subject sequence such that the percent identity is less than 100%. For example, the query sequence is at least 50%, at least 60%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the subject sequence. In the case of nucleic acid sequences, such changes include deletions, substitutions, or insertions of at least one nucleotide residue, which may occur at the 5' or 3' end of the query sequence, or anywhere between the ends, and may be interspersed individually among the nucleotide residues in the query sequence, or in one or more adjacent groups within the query sequence. In the case of amino acid sequences, such changes include deletions, substitutions (including conservative and non-conservative substitutions) or insertions of at least one amino acid residue, which may occur at the amino- or carboxy-terminus of the query sequence, or anywhere in between, and may be scattered individually among the amino acid residues in the query sequence, or in one or more contiguous groups within the query sequence.

[0030] Antibody sequences may be % identical over the entire length of the query sequence, including the CDRs. Alternatively, the % identity may exclude one or more or all of the CDRs, e.g., all of the CDRs are 100% identical to the subject sequence, with the % identity variation being in the remainder of the query sequence, e.g., framework sequences, such that the CDR sequences are fixed and unaltered.

[0031] In some embodiments, the anti-BCMA antigen binding protein comprises a heavy chain variable region (VH) of SEQ ID NO:7 and a light chain variable region (VL) of SEQ ID NO:8.

[0032] [ka]

[0033] [ka]

[0034] In some embodiments, the anti-BCMA antigen binding protein comprises a heavy chain (H) of SEQ ID NO:9 and a light chain (L) of SEQ ID NO:10.

[0035] [ka]

[0036] [ka]

[0037] In some embodiments, the anti-BCMA antigen binding protein is a T cell redirecting antibody (BiTE) with dual inhibition of the BCMA receptor and the CD3 receptor, such as teclistamab (Pillarisetti et al., Blood Advances 4, 4538-49, 2020) and blinatumomab, AMG424, GBR1342, BFR4350A, AMG420, AMG701, erlanatamab (PF-06863135), REGN5458, TNB-383B (Alhallak et al., Cancers 13, 2853, 2021). In some embodiments, the anti-BCMA antigen binding protein is a defucosylated anti-BCMA antibody, such as SEA-BCMA (Van Epps et al., Cancer Res 2018;78(13 Suppl):Abstract nr 3833).

[0038] CAR-T cell therapy In some embodiments, the anti-BCMA antigen binding protein is a CAR-T cell therapy, such as bb2121, ALLO-715, or PBCAR269A. Raje et al., N. Engl. J. Med. 380, 1726-37, 2019); Abramson, Int. J. Mol. Sci. 21, 5192, 2020. The term "chimeric antigen receptor" ("CAR"), as used herein, refers to an engineered receptor consisting of an extracellular antigen binding region (usually derived from a monoclonal antibody or fragment thereof, e.g., VH and VL domains in scFv format), optionally a spacer region, a transmembrane region, and one or more intracellular effector domains. CARs are also called chimeric T cell receptors or chimeric immune receptors (CIRs). Genetic transfer of CARs into hematopoietic cells, such as T cells, redirects the specificity of the T cells to a desired cell surface antigen, resulting in a CAR-T therapy.

[0039] The term "spacer region" as used herein refers to an oligopeptide or polypeptide that functions to connect the transmembrane domain to the target binding domain. This region may also be called the "hinge region" or "stalk region". The size of the spacer can vary depending on the location of the target epitope to maintain a set distance (e.g., 14 nm) during CAR:target binding. The term "transmembrane domain" as used herein refers to the portion of the CAR molecule that crosses the cell membrane.

[0040] The term "intracellular effect domain" (also referred to as "signal transduction domain"), as used herein, refers to the domain in the CAR that is involved in intracellular signal transduction after the antigen-binding region binds to the target. The intracellular effect domain is involved in the activation of at least one of the normal effector functions of the immune cell in which the CAR is expressed. For example, the effector function of a T cell can be a helper activity, including cytolytic activity or secretion of cytokines.

[0041] It will be understood by those skilled in the art that the VH and / or VL domains disclosed herein may be incorporated into a CAR-T therapeutic, for example in the form of an scFv.

[0042] immune complex In some embodiments, the anti-BCMA antigen binding protein is used in an immunoconjugate. An "immunoconjugate" (interchangeably referred to as an "antibody drug conjugate", "ADC", or "antigen binding protein drug conjugate") comprises an anti-BCMA antigen binding protein conjugated to one or more agents, such as a cytotoxin, e.g., a chemotherapeutic agent, an immunotherapeutic agent, a growth inhibitory agent, a toxin (e.g., a protein toxin such as a bacterial, fungal, plant, or animal derived enzymatically active toxin, or a fragment thereof), an antiviral agent, a radioisotope (i.e., a radioconjugate), an antibiotic, or a small interfering RNA (siRNA).

[0043] In some embodiments, the immunoconjugate has the general structure: ABP-((Linker) n -Ctx) m During the ceremony, ABP is anti-BCMA antigen-binding protein; the linker is absent or is any cleavable or non-cleavable linker; Ctx is any cytotoxin described herein; n is 0, 1, 2, or 3; and m is 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10.

[0044] Examples of linkers include Val-Cit linkers (e.g., Val-Cit-PAB-OH, Fmoc-Val-Cit-PAB-OH, Fmoc-Val-Cit-PAB-PNP, Boc-Val-Cit, Boc-Val-Cit-PAB, Boc-Val-Cit-PA B-PNP, MC(C5)-Val-Cit, MC-Val-Cit-PAB-OH, MC-Val-Cit-PAB-PNP, SPDP-Val-Cit-PAB-OH, SPDP-Val-Cit-PAB-PNP, Mal-PEG2-Val-Cit-PAB-OH, Ma l-PEG4-Val-Cit-PAB-OH, Mal-PEG1-Val-Cit-PAB-PNP, Mal-PEG4-Val-Cit-PAB-PNP, Mal-amide-PEG2-Val-Cit-PAB-OH, Mal-amide-PEG2-Val-Cit-PAB- PNP, Azide-PEG1-Val-Cit-PAB-OH, Azide-PEG3-Val-Cit-PAB-OH, Azide-PEG4-Val-Cit-PAB-OH, Azide-PEG3-Val-Cit-PAB-PNP, BCN-PEG3-Val-Cit, BCN-PEG 3-VC-PFP ester, DBCO-PEG4-Val-Cit-PAB-PNP, TCO-PEG4-Val-Cit-PAB-PNP; Val-Gly linkers (e.g., Boc-Val-Gly-OH, Mal-amido-PEG8-Val-Gly, Mal-amido-PEG8-val-gly-PAB-OH, Boc-Gly-Gly, Fmoc-Gly-Gly-OH, Boc-Gly-Gly-N-[4-(hydroxymethyl)phenyl], Boc-Gly-Gly-Gly-OH, (S)-benzyl 2-amino-N-[(carboxymethyl)phenyl]

[0036] Gly-Gly-Gly-Phe-Gly-OH, Fmoc-Gly-Gly-Gly-OH, Gly-Gly-Gly-PEG4-methyltetrazine, Gly-Gly-Gly-PEG3-TCO, Gly-Gly-Gly-PEG4-DBCO, TCO-PEG4-Fmoc-Gly-Gly-Gly, biotin-PEG11-Gly-Gly-Gly-amine, biotin-PEG12-Gly-Gly-Gly; Ala-Ala-Asn linkers (e.g.,Fmoc-Ala-Pro-OH, Fmoc-Ala-Ser(Psi(Me,Me)Pro)-OH, Fmoc-PEG4-Ala-Ala-Asn-PAB, azido-PEG5-Ala-Ala-Asn-PAB, Fmoc-PEG3-Ala-Ala-Asn(Trt)-PAB, azido-PEG4-Ala-Ala-Asn(Trt)-PAB, Fmoc-PEG3-Ala-Ala-Asn(Trt)-PAB-PNP; sulfone-PEG-acid linkers (e.g. For example, bis-sulfone-PEG4-acid, bis-sulfone-PEG8-acid, bis-sulfone-PEG12-acid, active-mono-sulfone-PEG8-acid; sulfone-PEG-NHS ester linkers (for example, bis-sulfone NHS ester, bis-sulfone-PEG4-NHS ester, bis-sulfone-PEG8-NHS ester, bis-sulfone-PEG12-NHS ester); PEG linkers (for example, alkyne PEG, amino PEG, aminooxy PEG, APN PEG, BCN-PEG, benzyl-PEG, biotin-PEG, bis-PEG-acid, bis-PEG-NHS, Boc-PEG, branched PEG, bromo-PEG, cleavable linker, DBCO PEG, diketone linker, DNP-PEG, DOTA PEG, fluorescent reagent, Fmoc PEG, hydroxy-PEG, iodo-PEG, lipid-PEG, m-PEG, maleimide linker, MeNH-PEG, non-PEG linker, PEG acid, PEG aldehyde, PEG azide, PEG hydrazide, PEG NHS ester, PEG PFP ester, PEG phosphonic acid, PEG silane, PEG sulfonic acid, PEG tosylate ester, PEG-X-PEG, peptide linker, poly-PEG, propargyl PEG, PROTAC PEG, SPDP PEG, sugar PEG, TCO-PEG, tetrazine-PEG, thiol PEG); disulfide linkers (e.g., aminoethyl-SS-ethyl alcohol, aminoethyl-SS-propionic acid, amino-SS-PEG12-acid, aminoethyl-SS-ethylamine, t-Boc-cystamine, azidoethyl-SS-propionic acid, azido-SS-PEG2-acid, azidoethyl-SS-propionic acid NHS ester, 3-[[2-[(4-azidobenzoyl)amino]ethyl]dithio]propanoic acid, azido-phenyl-amido-SS-sulfo-NHS,Azidoethyl-SS-ethyl alcohol, Azidoethyl-SS-ethylamine, Azidoethyl-SS-ethyl azide, Azido-PEG3-SS-PEG3-azide, Azidoethyl-PEG2-t-butyl ester, Propargyl-PEG1-SS-alcohol, Propargyl-PEG1-SS-PEG1-acid, Propargyl-PEG1-SS-PEG1-PFP ester, Propargyl-PEG1-SS-PEG1-propargyl, Propargyl-PEG1-SS-PEG1-t-butyl ester, 4-Azido-TFP-amide-SS-propion Acid, 4-Azido-TFP-Ami-SS-Sulfo-NHS, Acid-PEG2-SS-PEG2-acid, Acid-PEG3-SS-PEG3-acid, Acid-PEG4-SS-PEG4-acid, Acid-PEG6-SS-PEG6-acid, Boc-NH-Ethyl-SS-Propionic Acid, Boc-Aminooxy-Ethyl-SS-Propanol, Fmoc-NH-Ethyl-SS-Propionic Acid, Fmoc-NH-Ethyl-SS-Propionic Acid NHS Ester, Mal-NH-Ethyl-SS-Propionic Acid, (S)-2-Amino-4-(2-(Pyridin-2-yl)disulfanyl) Butanoic acid, N-(2,2,2-trifluoroacetyl)-3-[(2-aminoethyl)dithio]propanoic acid, Trifluoroacetamidoethyl-SS-propionic acid NHS ester, Hydroxy-PEG3-SS-PEG3-alcohol, m-PEG6-SS-PEG6-methyl, THP-SS-alcohol, THP-SS-PEG1-t-butyl ester, THP-SS-PEG1-Tos, 2-hydroxyethyl disulfide mono-tosylate, Bis-Tos-(2-hydroxyethyl disulfide), Biotin-SS-amine HCl salt, Azide do-SS-biotin, DBCO-SS-PEG3-biotin, biotin-PEG4-SS-acid, biotin-bisamide-SS-NHS, NHS-SS-biotin, sulfo-NHS-SS-biotin, biotin-PEG4-SS-NHS, bis-(norbornene-PEG23)-disulfide; photocleavable linkers (e.g., PC-biotin-PEG3-alkyne, PC-biotin-PEG4-PEG4-alkyne, PC-biotin-PEG3-azide, PC-biotin-PEG4-PEG3-azide, PC-biotin-PEG3-NHS carbonate,PC-biotin-PEG4, PC-biotin-PEG4-NHS carbonate, PC DBCO-PEG3-biotin, PC SPDP-NHS carbonate, PC alkyne-PEG4-NHS carbonate, PC Mal-NHS carbonate, PC azide-PEG3-NHS carbonate, PC azide-PEG11-NHS carbonate, 4-azido-TFP-amide-PEG4-acid; and enzyme-cleavable linkers (e.g., Mal-PEG2-Val-Cit-PAB-OH, Mal-PEG4-Val-Cit-PAB-OH, Mal-PEG1-Val-Cit-PAB-PNP, Mal-PEG4-Val-Cit-PAB-PNP, Mal-amide-PEG2-Val-Cit-PAB-OH, Mal-PEG4-Val-Cit-PAB-OH, Mal-PEG1 ...4-Val-Cit-PAB-PNP, Mal-amide-PEG2-Val-Cit-PAB-OH, Mal-PEG4- H, Mal-amide-PEG2-Val-Cit-PAB-PNP, azido-PEG1-Val-Cit-PAB-OH, azido-PEG3-Val-Cit-PAB-OH, azido-PEG4-Val-Cit-PAB-OH, azido-PEG3-Val-Cit-PAB-PNP, BCN-PEG3-Val-Cit, BCN-PEG3-VC-PFP ester, DBCO-PEG4-Val-Cit-PAB-PNP, TCO-PEG4-Val-Cit-PAB-PNP).

[0045] In some embodiments, the linker is 6-maleimidocaproyl (MC), maleimidopropanoyl (MP), valine-citrulline (val-cit), alanine-phenylalanine (ala-phe), p-aminobenzyloxycarbonyl (PAB), N-succinimidyl 4-(2-pyridylthio)pentanoate (SPP), N-succinimidyl 4-(N-maleimidomethyl)cyclohexane-1 carboxylate (SMCC), or N-succinimidyl (4-iodo-acetyl)aminobenzoate (SIAB).

[0046] In some embodiments, the immunoconjugate comprises an anti-BCMA monoclonal antibody linked to a cytotoxin, such as monomethyl auristatin E (MMAE), D8-MMAE, MMAF hydrochloride, PF-06380101, D8-MMAF hydrochloride, dolastatin 10, MMAF sodium, auristatin E, MMAF-OMe, MMAF, PF-06380101. D8, calicheamicin, SN-38, camptothecin, Dxd, 7-MAD-MDCPT, Top1 inhibitor 1, doxorubicin hydrochloride, daunorubicin hydrochloride, aldoxorubicin, PNU-159682, Daun02, daunorubicin, PNU-159682 carboxylic acid, DMEA-PNU-159682, duocarmycin DM, duocarmycin DM free base, duocarmycin TM, DC1SMe duocarmycin A, duocarmycin SA, DC1, (+)-CBI-CDP12, duocarmycin analog, duocarmycin MB, SG3199, Py-MPB-amino-C3-PBD, aniline-MPB-amino-C3-PBD, dimethyl-SGD-1882, paclitaxel, methotrexate, α-amanitin, tartopurine, tartopurine hydrochloride, tartopurine trifluoroacetate, 10-deacetyl 7-xylosylpaclitaxel, C11, β-amanitin, tubulysin A, and telomestatin.

[0047] In some embodiments, the immunoconjugate comprises an anti-BCMA monoclonal antibody linked to dovaline-valine-dolaisoleunine-dolaproine-phenylalanine (MMAF) or monomethylauristatin E (MMAE). In other embodiments, the immunoconjugate comprises a monoclonal antibody linked to MMAF or MMAE by a maleimidocaproyl (MC) linker as shown in the following structure: [ka]

[0048] In some embodiments, the immunoconjugate is belantamab mafodotin. Belantamab mafodotin comprises an anti-BCMA antibody conjugated to a microtubule inhibitor (monomethyl auristatin F, MMAF) via a maleimidocaproyl linker and is described in the US package insert for BLENREP® (belantamab mafodotin-blmf). As described in the current package insert, the recommended dose of BLENREP® is 2.5 mg / kg as an intravenous infusion over about 30 minutes once every three weeks. In some embodiments, the combination therapy comprises belantamab mafodotin at a dose of at least about 0.5 mg / kg, at least about 1.0 mg / kg, at least about 1.25 mg / kg, at least about 1.7 mg / kg, at least about 1.92 mg / kg, or at least about 4.6 mg / kg. In some embodiments, subjects are administered an anti-BCMA antigen binding protein at a dose of 1.9mg / kg, Q3 / 4W, 1.4mg / kg, Q6 / 8W; 1.9mg / kg, Q6 / 8W; 1.0mg / kg, Q3 / 4W, 1.4mg / kg, Q3 / 4W, 1.4mg / kg, Q9W, 1.4mg / kg, Q12W, or 1.0, Q12W.

[0049] Immunomodulatory imide drugs Examples of IMiDs include, but are not limited to, thalidomide (e.g., THALOMID®), lenalidomide (e.g., REVLIMID®), and pomalidomide (e.g., POMALYST®).

[0050] Corticosteroids Examples of corticosteroids include, but are not limited to, dexamethasone (e.g., DECADRON®, DEXASONE®, DIODEX®, HEXADROL®, MAXIDEX®), prednisone (e.g., DELTASONE®), and methylprednisolone (e.g., MEDROL®).

[0051] Anti-CD38 antibody Examples of anti-CD38 antibodies include, but are not limited to, isatuximab or isatuximab-irfc (e.g., SARCLISA®) and daratumumab (e.g., DARZALEX®, DARZALEX FASPRO®).

[0052] Proteasome inhibitors Examples of proteasome inhibitors include, but are not limited to, bortezomib (e.g., VELCADE®), ixazomib (e.g., NINLARO®), carfilzomib (e.g., KYPROLIS®), oprozomib, and delanzomib.

[0053] γ-Secretase Inhibitors Examples of gamma-secretase inhibitors include, but are not limited to, nirogacestat (PF-0308014), crenigacestat (LY3039478), CB-103, tarenflurvir, semagacestat (LY450139), RG-4733, EVP-0962, avagacestat, MK-0752, and BMS-906024, and derivatives and polymorphs thereof.

[0054] In some embodiments, the gamma-secretase inhibitor is nirogacestat. Nirogacestat, (S)-2-(((S)-6,8-difluoro-1,2,3,4-tetrahydronaphthalen-2-yl)amino)-N-(1-(2-methyl-1-(neopentylamino)propan-2-yl)-1H-imidazol-4-yl)pentamide, has the following chemical structure: [ka]

[0055] Form A polymorph of nirogacestat dihydrobromide (dihydrobromide of (S)-2-(((S)-6,8-difluoro-1,2,3,4-tetrahydronaphthalen-2-yl)amino)-N-(1-(2-methyl-1-(neopentylamino)propan-2-yl)-1H-imidazol-4-yl)pentanamide of formula (I) [ka]

[0056] Nirogacestat dihydrobromide Form A is characterized by an XRPD pattern with peaks at 8.8±0.2 degrees 2θ, 9.8±0.2 degrees 2θ, and 23.3±0.2 degrees 2θ.

[0057] In one embodiment, the crystalline Form A of nirogacestat dihydrobromide is anhydrous. In another embodiment, the melting point of the crystalline Form A of nirogacestat dihydrobromide is about 254° C.

[0058] In another embodiment, Form A of nirogacestat dihydrobromide is characterized by an XRPD pattern having peaks at 8.8±0.2°(2θ), 9.8±0.2°(2θ), and 23.3±0.2°(2θ) as measured with Cu Ka radiation. In another embodiment, Form A of nirogacestat dihydrobromide is characterized by an XRPD pattern having peaks at 8.8±0.2°(2θ), 9.8±0.2°(2θ), 23.3±0.2°(2θ), 25.4±0.2°(2θ), 28.0±0.2°(2θ), and 29.3±0.2°(2θ) as measured with Cu Ka radiation.

[0059] In another embodiment, nirogacestat dihydrobromide Form A is characterized by an XRPD pattern with peaks at 8.8±0.2 degrees 2θ, 9.8±0.2 degrees 2θ, 20.0±0.2 degrees 2θ, 23.3±0.2 degrees 2θ, 25.4±0.2 degrees 2θ, 28.0±0.2 degrees 2θ, 29.3±0.2 degrees 2θ, and 32.5±0.2 degrees 2θ, as measured with Cu Ka radiation.

[0060] Examples of combination therapy and its use Combination Therapy for Newly Diagnosed Multiple Myeloma In some embodiments, the combination therapy is administered to treat the patient who is newly diagnosed with multiple myeloma.In some of these embodiments, the patient is ineligible for autologous stem cell transplantation.In some embodiments, the second combination therapy is administered to the treated patient as maintenance therapy.

[0061] "Treating," as used herein, refers to administering one or more active agents that are intended or intended to alleviate, ameliorate, improve, or affect the alleviation of one or more symptoms or effects associated with a disorder, such as multiple myeloma, and / or slow the progression of a disorder, such as multiple myeloma. For example, in some embodiments, the combination therapy of the present disclosure reduces ocular toxicity (e.g., corneal epithelial changes, dry eyes, irritation, redness, blurred vision, photophobia, changes in visual acuity) when compared to administering a therapeutically effective amount of an anti-BCMA antigen binding protein (e.g., belantamab mafodotin). Detection of ocular toxicity may be determined by ophthalmic examination by an ophthalmologist or optometrist before, during, and / or after treatment.

[0062] An eye examination may include one or more of the following: 1. Best corrected visual acuity, 2. Documentation of subjective refraction and the method used to obtain best corrected visual acuity 3. Your current eyeglass prescription (if applicable); 4. Intraocular pressure measurement, 5. Anterior segment (slit lamp) examination, including corneal fluorescein staining and lens examination; 6. Dilated eye examination and / or 7. Ocular Surface Disease Index (OSDI), a visual function questionnaire that assesses the impact of potential ocular changes in vision on function and health-related quality of life.

[0063] In some embodiments, reducing ocular toxicity refers to reducing the severity of adverse corneal reactions or the grade of treatment-related corneal toxicity as determined according to the KVA scale. [Table 2]

[0064] In some embodiments, as described in more detail below, patients are treated with a combination therapy comprising a BCMA antigen binding protein, e.g., belantamab mafodotin; a proteasome inhibitor, e.g., bortezomib; an IMiD, e.g., lenalidomide; and a corticosteroid, e.g., dexamethasone, in three-week cycles for up to eight cycles ("induction therapy"). In some embodiments, the length of one cycle is 21 days for induction treatment cycles. In some embodiments, such treatment is followed by a combination therapy comprising a BCMA antigen binding protein, an IMiD, and a corticosteroid, in four-week cycles ("maintenance therapy"). In some embodiments, the length of one cycle is 28 days for maintenance treatment cycles. In some embodiments, belantamab mafodotin is administered in combination with bortezomib, lenalidomide, and dexamethasone ("VRd") every three weeks (Q3W), every six weeks (Q6W), or every nine weeks (Q9W) until cycle 8, and then every four weeks (Q4W), every eight weeks (Q8W), or every twelve weeks (Q12W) thereafter in combination with lenalidomide and dexamethasone ("Rd").

[0065] In some embodiments, the combination therapy further comprises a gamma-secretase inhibitor, such as nirogacestat.

[0066] Belantamab mafodotin administration In some embodiments, patients are treated with belantamab mafodotin at a dose of 1.9 mg / kg (Q3 / 4W).In some embodiments, patients are treated with belantamab mafodotin at a dose of 1.9 mg / kg on day 1 of each cycle.

[0067] In some embodiments, patients are treated with belantamab mafodotin at a dose of 1.4 mg / kg (Q6 / 8W).In some embodiments, patients are treated with belantamab mafodotin at a dose of 1.4 mg / kg on day 1 of every 2 cycles.

[0068] In some embodiments, patients are treated with belantamab mafodotin (Q6 / 8W) at a dose of 1.9 mg / kg. In some embodiments, patients are treated with belantamab mafodotin (Q6 / 8W) at a dose of 1.9 mg / kg on day 1 of every 2 cycles.

[0069] In some embodiments, patients are treated with belantamab mafodotin Q3 / 4W at a dose of 1.0 mg / kg. In some embodiments, patients are treated with belantamab mafodotin Q3 / 4W at a dose of 1.0 mg / kg on day 1 of each cycle.

[0070] In some embodiments, patients are treated with belantamab mafodotin at a dose of 1.4 mg / kg (Q3 / 4W). In some embodiments, patients are treated with belantamab mafodotin at a dose of 1.4 mg / kg on day 1 of each cycle.

[0071] In some embodiments, patients are treated with belantamab mafodotin at a dose of 1.4 mg / kg on day 1 of cycle 1, then, starting with cycle 4, with belantamab mafodotin at a dose of 1.0 mg / kg on day 1 of every third cycle.

[0072] In some embodiments, patients are treated with belantamab mafodotin at a dose of 1.9 mg / kg on day 1 of cycle 1, then, starting with cycle 4, with belantamab mafodotin at a dose of 1.4 mg / kg on day 1 of every third cycle.

[0073] In some embodiments, patients are treated with belantamab mafodotin at a dose of 1.9 mg / kg on day 1 of cycles 1 and 4, then, starting with cycle 7, with belantamab mafodotin at a dose of 1.4 mg / kg on day 1 of every third cycle.

[0074] In some embodiments, patients are treated with belantamab mafodotin at a dose of 1.4 mg / kg on day 1 of cycles 1 and 3, then, starting with cycle 6, with belantamab mafodotin at a dose of 1.0 mg / kg on day 1 of every third cycle.

[0075] In some embodiments, patients are treated with belantamab mafodotin at a dose of 1.0 mg / kg on day 1 of cycles 1 and 5, then, starting with cycle 9, with belantamab mafodotin at a dose of 1.0 mg / kg on day 1 of every third cycle.

[0076] In some embodiments, patients are treated with belantamab mafodotin at a dose of 1.9 milligrams per kilogram (mg / kg) administered intravenously (IV) every three weeks (Q3W) on day 1 of every 21-day cycle in combination with VRd (bortezomib, lenalidomide, and dexamethasone, administered as described below) for the first 8 cycles. From cycle 9 onwards, patients are treated with belantamab mafodotin at a dose of 1.9 mg / kg administered intravenously every four weeks (Q4W) on day 1 of every 28-day cycle in combination with Rd (lenalidomide and dexamethasone, administered as described below).

[0077] In some embodiments, patients are treated with belantamab mafodotin at a dose of 1.4 mg / kg administered intravenously every 6 weeks (Q6W) in combination with VRd on day 1 of every two 21-day cycles for the first 8 cycles. From cycle 9 onwards, patients are treated with belantamab mafodotin at a dose of 1.4 mg / kg administered intravenously every 8 weeks (Q8W) in combination with Rd on day 1 of every two 28-day cycles.

[0078] In some embodiments, patients are treated with belantamab mafodotin at a dose of 1.9 mg / kg, Q6W, in combination with VRd, administered intravenously on day 1 of every two 21-day cycles for the first 8 cycles. From cycle 9 onwards, patients are treated with belantamab mafodotin at a dose of 1.9 mg / kg, Q8W, in combination with Rd, administered intravenously on day 1 of every two 28-day cycles.

[0079] In some embodiments, patients are treated with belantamab mafodotin at a dose of 1.0 mg / kg, Q3W, in combination with VRd, administered intravenously on day 1 of every 21-day cycle for the first 8 cycles. From cycle 9 onwards, patients are treated with belantamab mafodotin at a dose of 1.0 mg / kg, Q4W, in combination with Rd, administered intravenously on day 1 of every 28-day cycle.

[0080] In some embodiments, patients are treated with belantamab mafodotin at a dose of 1.4 mg / kg, Q3W, in combination with VRd, for the first 8 cycles. From cycle 9 onwards, patients are treated with belantamab mafodotin at a dose of 1.4 mg / kg, Q4W, in combination with Rd, on day 1 of every 28-day cycle.

[0081] In some embodiments, patients are treated with belantamab mafodotin at a dose of 1.4 mg / kg, administered intravenously, on day 1 of cycle 1 for the first 8 cycles, then from cycle 4 onwards, belantamab mafodotin at a dose of 1.0 mg / kg, administered intravenously, on day 1 of every 3 cycles in combination with VRd, with each cycle being 21 days long. From cycle 9 onwards, patients are treated with belantamab mafodotin at a dose of 1.0 mg / kg, administered intravenously, on day 1 of every 3 cycles in combination with Rd, with each cycle being 28 days long.

[0082] In some embodiments, patients are treated with belantamab mafodotin at a dose of 1.9 mg / kg, administered intravenously, on day 1 of cycle 1 for the first 8 cycles, then from cycle 4 onwards, belantamab mafodotin at a dose of 1.4 mg / kg, administered intravenously, on day 1 of every 3 cycles in combination with VRd, with each cycle being 21 days long. From cycle 9 onwards, patients are treated with belantamab mafodotin at a dose of 1.4 mg / kg, administered intravenously, on day 1 of every 3 cycles in combination with Rd, with each cycle being 28 days long.

[0083] In some embodiments, patients are treated with belantamab mafodotin at a dose of 1.9 mg / kg, administered intravenously, on day 1 of cycles 1 and 4, in combination with VRd for the first 8 cycles, and then from cycle 7 onwards, with belantamab mafodotin at a dose of 1.4 mg / kg, administered intravenously, on day 1 of every 3 cycles, each cycle being 21 days long. From cycle 9 onwards, patients are treated with belantamab mafodotin at a dose of 1.4 mg / kg, administered intravenously, on day 1 of every 3 cycles, each cycle being 28 days long, in combination with Rd.

[0084] In some embodiments, patients are treated with belantamab mafodotin at a dose of 1.4 mg / kg, administered intravenously, on day 1 of cycles 1 and 3, in combination with VRd for the first 8 cycles, and then, starting with cycle 6, with belantamab mafodotin at a dose of 1.0 mg / kg, administered intravenously, on day 1 of every 3 cycles, each cycle being 21 days long. From cycle 9 onwards, patients are treated with belantamab mafodotin at a dose of 1.0 mg / kg, administered intravenously, on day 1 of every 3 cycles, each cycle being 28 days long, in combination with Rd.

[0085] In some embodiments, patients are treated with belantamab mafodotin at a dose of 1.0 mg / kg administered intravenously in combination with VRd on day 1 of cycles 1 and 5, with each cycle being 21 days long, for the first 8 cycles. From cycle 9 onwards, patients are treated with belantamab mafodotin at a dose of 1.0 mg / kg administered intravenously in combination with Rd on day 1 of every 3 cycles, with each cycle being 28 days long.

[0086] In some embodiments, patients are treated with belantamab mafodotin at a dose of 1.9 mg / kg or 2.5 mg / kg, Q9W, in combination with VRd, administered intravenously on day 1 of every three 21-day cycles for the first eight cycles. From cycle 9 onwards, patients are treated with belantamab mafodotin at a dose of 1.9 mg / kg or 2.5 mg / kg, Q12W, in combination with Rd, administered intravenously on day 1 of every three 28-day cycles.

[0087] In some embodiments, patients are treated with belantamab mafodotin at a total dose of 1.9 mg / kg or 2.5 mg / kg intravenously (divided into two equal doses of 0.95 mg / kg or 1.25 mg / kg administered on days 1 and 8) Q6W for every two 21-day cycles in combination with VRd for the first eight cycles. From cycle 9 onwards, patients are treated with belantamab mafodotin at a total dose of 1.9 mg / kg or 2.5 mg / kg intravenously (divided into two equal doses of 0.95 mg / kg or 1.25 mg / kg administered on days 1 and 8) Q8W for every two 28-day cycles in combination with Rd.

[0088] In some embodiments, patients are treated with belantamab mafodotin at a dose of 2.5 mg / kg Q6W in combination with VRd for the first 8 cycles. From cycle 9 onwards, patients are treated with belantamab mafodotin at a dose of 2.5 mg / kg Q8W in combination with Rd on day 1 of every 21-day cycles.

[0089] The specifications for belantamab-mafodotin treatment are shown in Table 1. [Table 3]

[0090] In some embodiments, when administered on Day 1, belantamab mafodotin is administered as the first agent in the clinic (prior to VRd or Rd) as one complete dose on Day 1, with a 30-60 minute infusion followed by a 1-2 hour rest period. A dose of bortezomib is administered approximately 1 hour after the belantamab mafodotin infusion is completed.

[0091] If a patient is treated on Day 1 of each cycle (Q3 / 4W), if a scheduled dose of belantamab mafodotin is withheld / missed for any reason, the next dose may be administered on Day 1 of the next scheduled 21-day or 28-day cycle, as long as the interval between two consecutive doses is at least 21 (± 3) days or 28 (± 3) days, respectively.

[0092] If patients are treated on Day 1 of every 2 cycles (Q6 / 8W), if a scheduled dose of belantamab mafodotin is withheld / missed for any reason, the next dose may be administered on Day 1 of the next scheduled 21-day or 28-day cycle, as long as the interval between two consecutive doses is at least 42 (± 3) days or 56 (± 3) days, respectively.

[0093] If patients are treated on Day 1 of every 3rd cycle (Q9 / 12W), if a scheduled dose of belantamab mafodotin is withheld / missed for any reason, the next dose may be administered on Day 1 of the next scheduled 21-day or 28-day cycle, as long as the interval between two consecutive doses is at least 63 (± 3) days or 84 (± 3) days, respectively.

[0094] The dose of belantamab mafodotin in combination with VRd for both induction and maintenance treatment is based on actual body weight calculated at baseline (Day 1 of Cycle 1). If the change in body weight is greater than 10%, the dose can be recalculated based on actual body weight at the time of dosing.

[0095] Bortezomib Administration Bortezomib for injection is supplied in 10 mL vials containing 3.5 mg of bortezomib as a white to off-white cake or powder. The starting dose of bortezomib is 1.3 mg / m 2 Dose reductions and interruptions are permitted according to the bortezomib label (e.g., Error! Reference source not found., 2021; Error! Reference source not found., 2019). Decisions regarding dose reductions or changes can be made by the treating physician.

[0096] On the day that belantamab mafodotin is administered, if the patient is clinically stable, bortezomib will be administered subcutaneously approximately 1 hour after completion of the belantamab mafodotin infusion. In patients who experience an infusion-related reaction (IRR) during or after belantamab mafodotin administration, administration of bortezomib will be delayed until the IRR has resolved and the patient is deemed clinically stable.

[0097] At least 72 hours should elapse between each successive dose of bortezomib. If a bortezomib dose is delayed, the next dose will be adjusted to account for the delay, as all bortezomib doses must be separated by at least 72 hours. Any doses that need to be withheld will be skipped and will not be made up later in the cycle. If more than 72 hours have passed since the last dose, there is a time window of ±1 day for each individual dose within the cycle. The site of each subcutaneous (SC) injection will be rotated. The new injection will be given at least 2.5 cm (1 inch) away from the old site, into an area that is tender, bruised, erythematous, or indurated. If local injection site reactions occur after SC bortezomib administration, a less concentrated solution (1 mg / mL instead of 2.5 mg / mL) may be administered SC. Alternatively, the IV route of administration may be considered for patients who are intolerant to SC injections or who develop significant edema at the candidate SC injection site.

[0098] The dose of bortezomib is based on the patient's body surface area (BSA). The reconstituted concentration of bortezomib for subcutaneous administration (2.5 mg / mL) is greater than the reconstituted concentration of bortezomib for intravenous administration (1 mg / mL). The patient's BSA (units m 2 After calculating the total volume (mL) of reconstituted bortezomib to be administered, the following formula can be used to calculate the total volume (mL) of reconstituted bortezomib to be administered: 2 ) × patient's BSA (m 2 )]÷[2.5 mg / mL]=total volume of bortezomib to be administered (mL). For intravenous administration (concentration 1 mg / mL): [bortezomib dose (mg / m 2 ) × patient's BSA (m 2 )]÷[1mg / mL]=total volume of bortezomib to be administered (mL).

[0099] Lenalidomide administration Lenalidomide is available in capsule form for oral administration at 5 mg, 10 mg, 15 mg, 20 mg, and 25 mg. Details of the drug presentation can be found in the representative information for lenalidomide. Lenalidomide is administered orally at fixed dosage levels of 25 mg or 10 mg, depending on renal function. Patients with an estimated glomerular filtration rate (eGFR) of 60 mL / min / 1.73 m 2 Patients with eGFR >30–60 mL / min / 1.73 m are given 25 mg. 2 Patients who are ≥ 1 will receive 10 mg.

[0100] Dexamethasone administration Dexamethasone is available as a tablet for oral administration. Details of the pharmaceutical presentation can be found in the representative information on dexamethasone. Dexamethasone is administered orally at fixed dosage levels of 20 mg for cycles 1-8 and 40 mg for cycles 9 and beyond. Dexamethasone is taken at the same time on the day of administration and may be taken at home. For patients who are older than 75 years, underweight (BMI < 18.5), have poorly controlled diabetes mellitus, or have a history of intolerance / adverse events (AEs) to steroid therapy, dexamethasone dosing may be administered on the above days at doses of 10 mg (cycles 1-8) and 20 mg (cycles 9 and beyond).

[0101] Administration of Nirogacestat Independently, nirogacestat can be administered as part of any of the above combination therapies.The dosage of nirogacestat can be, for example, at least about 50mg, at least about 100mg, at least about 150mg, at least about 200mg, or at least 250mg, administered once or twice a day.In some embodiments, 100mg of nirogacestat is administered twice a day.

[0102] Combination therapies of anti-BCMA antigen binding proteins and gamma-secretase inhibitors, including dosages, duration of treatment, and time course between administration of the two agents, are disclosed in WO 2020 / 208572. In some embodiments, the combination therapy is nirogacestat at a dose of at least about 50 mg, at least about 100 mg, at least about 150 mg, at least about 200 mg, or at least about 250 mg.

[0103] Methods for Treating Newly Diagnosed Multiple Myeloma The present disclosure provides a method of treating multiple myeloma in a subject. In some embodiments, the subject is newly diagnosed with multiple myeloma. In some of these embodiments, the subject is ineligible for autologous stem cell transplantation.

[0104] In some embodiments, the method comprises administering to a subject: (a) a therapeutically effective amount of an anti-BCMA antigen binding protein; (b) a therapeutically effective amount of a proteasome inhibitor; (c) a therapeutically effective amount of an immunomodulatory imido drug; and (d) a therapeutically effective amount of a corticosteroid.

[0105] In some embodiments, the anti-BCMA antigen binding protein is belantamab mafodotin, and the belantamab mafodotin is administered intravenously to the subject according to a schedule selected from the group consisting of: (i) belantamab mafodotin at a dose of 1.9 mg / kg administered on day 1 of each cycle for 8 induction treatment cycles, where each induction treatment cycle is 21 days long; (ii) belantamab mafodotin at a dose of 1.4 mg / kg administered on day 1 of every 2nd cycle for 8 induction treatment cycles. (iii) for eight induction cycles, belantamab mafodotin at a dose of 1.9 mg / kg is administered on day 1 of every two cycles, where each induction cycle is 21 days; (iv) for eight induction cycles, belantamab mafodotin at a dose of 1.0 mg / kg is administered on day 1 of every cycle, where each induction cycle is 21 days; (v) for eight induction cycles, belantamab mafodotin at a dose of 1.4 mg / kg is administered on day 1 of every two cycles, where each induction cycle is 21 days; (vi) for eight induction cycles, belantamab mafodotin at a dose of 1.4 mg / kg is administered on day 1 of cycle 1, and from cycle 4, belantamab mafodotin at a dose of 1.0 mg / kg is administered on day 1 of every third cycle, wherein each induction cycle is 21 days; (vii) for eight induction cycles, belantamab mafodotin at a dose of 1.9 mg / kg is administered on day 1 of cycle 1, and from cycle 4, belantamab mafodotin at a dose of 1.9 mg / kg is administered on day 1 of cycle 1, and (viii) for eight induction cycles, belantamab mafodotin at a dose of 1.9 mg / kg is administered on day 1 of cycles 1 and 4, and from cycle 7, belantamab mafodotin at a dose of 1.4 mg / kg is administered on day 1 of every three cycles, where each induction cycle is 21 days; (ix) for eight induction cycles, belantamab mafodotin at a dose of 1.(x) belantamab mafodotin at a dose of 1.0 mg / kg is administered on day 1 of cycles 1 and 3, and from cycle 6, belantamab mafodotin at a dose of 1.0 mg / kg is administered on day 1 of every 3 cycles, where each induction cycle is 21 days; (x) for 8 induction cycles, belantamab mafodotin at a dose of 1.0 mg / kg is administered on day 1 of cycles 1 and 5, where each induction cycle is 21 days; the proteasome inhibitor is bortezomib, and for 8 induction cycles, bortezomib is administered at a dose of 1.3 mg / m. 2 the immunomodulatory imide drug is lenalidomide, and the lenalidomide is administered subcutaneously (SC) to the subject on days 1, 4, 8, and 11 of every 21-day cycle at a dose of 25 mg for eight induction treatment cycles, and the lenalidomide is administered orally to the subject on each of days 1-14 of each 21-day cycle at a dose of 25 mg for eight induction treatment cycles, or (ii) to the subject with an eGFR between 30 and 60 mL / min / 1.73 m 2 the corticosteroid is dexamethasone, and the dexamethasone is (i) orally administered to the subject at a dose of 20 mg on days 1, 2, 4, 5, 8, 9, 11, and 12 of each 21-day cycle for eight induction treatment cycles, or (ii) orally administered to the subject at a dose of 10 mg on days 1, 2, 4, 5, 8, 9, 11, and 12 of each 21-day cycle for eight induction treatment cycles, if the subject is older than 75 years of age or has a body mass index (BMI) less than 18.5.

[0106] In some embodiments, the method further comprises administering to the subject, after the eight induction treatment cycles, a maintenance therapy comprising: (a) a therapeutically effective amount of an anti-BCMA antigen binding protein; (b) a therapeutically effective amount of an immunomodulatory imide drug; and (c) a therapeutically effective amount of a corticosteroid. In some embodiments, the maintenance therapy does not include a proteasome inhibitor. In some embodiments, the maintenance therapy does not include bortezomib.

[0107] In some embodiments of the maintenance therapy, the anti-BCMA antigen binding protein is belantamab mafodotin, and the belantamab mafodotin is administered intravenously according to a schedule selected from the group consisting of: (i) on day 1 of every 28-day cycle; (ii) on day 1 of every two 28-day cycles; and (iii) on day 1 of every three 28-day cycles; the immunomodulatory imide drug is lenalidomide, and the lenalidomide is administered (i) at a dose of 25 mg on each of days 1-21 of each 28-day cycle, or (ii) when the subject's eGFR is between 30 and 60 mL / min / 1.73 m 2 is orally administered to the subject at a dose of 10 mg on days 1 to 21 of each 28 day cycle; and the corticosteroid is dexamethasone, which is orally administered to the subject (i) at a dose of 40 mg on days 1, 8, 15, and 22 of each 28 day cycle, or (ii) at a dose of 20 mg on days 1, 8, 15, and 22 of each 28 day cycle, if the subject is older than 75 years of age or has a body mass index (BMI) less than 18.5.

[0108] In some embodiments, the method comprises administering to the subject belantamab mafodotin, where the belantamab mafodotin is administered intravenously to the subject on day 1 of each cycle at a dose of 1.9 mg / kg for eight induction treatment cycles, where each induction treatment cycle is 21 days; and administering bortezomib, where the bortezomib is administered at a dose of 1.3 mg / m 2administered subcutaneously (SC) to the subject on days 1, 4, 8, and 11 of every 21-day cycle, wherein lenalidomide is (i) administered orally to the subject on each of days 1-14 of each 21-day cycle at a dose of 25 mg, or (ii) administered to the subject when the subject's eGFR is between 30 and 60 mL / min / 1.73 m 2 orally administered to the subject at a dose of 10 mg on each of days 1-14 of each 21-day cycle, for eight induction treatment cycles; wherein dexamethasone is (i) orally administered to the subject at a dose of 20 mg on days 1, 2, 4, 5, 8, 9, 11, and 12 of each 21-day cycle, for eight induction treatment cycles, or (ii) orally administered to the subject at a dose of 10 mg on days 1, 2, 4, 5, 8, 9, 11, and 12 of each 21-day cycle, for eight induction treatment cycles, if the subject is older than 75 years of age or has a body mass index (BMI) less than 18.5, for eight induction treatment cycles. orally administered to the subject on days 5, 8, 9, 11, and 12 of each induction treatment cycle; further comprising administering a maintenance therapy to the subject after the eight induction treatment cycles, the maintenance therapy comprising belantamab mafodotin, wherein belantamab mafodotin is administered intravenously to the subject on day 1 of each cycle at a dose of 1.9 mg / kg starting with cycle 9, each cycle being 28 days long; and comprising lenalidomide, wherein lenalidomide (i) is administered orally to the subject on each of days 1-21 of each 28-day cycle at a dose of 25 mg, or (ii) the subject's eGFR is between 30 and 60 mL / min / 1.73 m. 2 is orally administered to the subject at a dose of 10 mg on days 1 to 21 of each 28 day cycle, if the subject is older than 75 years of age or has a body mass index (BMI) of less than 18.5; and comprises dexamethasone, which is orally administered to the subject at (i) a dose of 40 mg on days 1, 8, 15, and 22 of each 28 day cycle, if the subject is older than 75 years of age or has a body mass index (BMI) of less than 18.5, if the subject is orally administered to the subject at a dose of 20 mg on days 1, 8, 15, and 22 of each 28 day cycle.

[0109] In some embodiments, the method comprises administering to the subject belantamab mafodotin, where the belantamab mafodotin is administered intravenously to the subject on day 1 of every 2 cycles at a dose of 1.4 mg / kg for 8 induction treatment cycles, each induction treatment cycle being 21 days; and administering bortezomib, where the bortezomib is administered at a dose of 1.3 mg / m for 8 induction treatment cycles. 2 administered subcutaneously (SC) to the subject on days 1, 4, 8, and 11 of every 21-day cycle at a dose of 25 mg for eight induction treatment cycles; or administering lenalidomide orally to the subject on each of days 1-14 of each 21-day cycle at a dose of 25 mg for eight induction treatment cycles; or (ii) administering to the subject an eGFR of 30-60 mL / min / 1.73 m 2 orally administered to the subject at a dose of 10 mg on each of days 1 to 14 of each 21-day cycle, for eight induction treatment cycles; wherein dexamethasone is (i) orally administered to the subject at a dose of 20 mg on days 1, 2, 4, 5, 8, 9, 11, and 12 of each 21-day cycle, for eight induction treatment cycles, or (ii) orally administered to the subject at a dose of 10 mg on days 1, 2, 4, 5, 8, 9, 11, and 12 of each 21-day cycle, for eight induction treatment cycles, if the subject is older than 75 years of age or has a body mass index (BMI) less than 18.5, for eight induction treatment cycles. orally administered to the subject on days 8, 9, 11, and 12 of each induction treatment cycle; further comprising administering a maintenance therapy to the subject after the eight induction treatment cycles, the maintenance therapy comprising belantamab mafodotin, which is administered intravenously to the subject at a dose of 1.4 mg / kg on day 1 of every two cycles starting with cycle 9, each cycle being 28 days long; and comprising lenalidomide, which (i) is administered orally to the subject at a dose of 25 mg on each of days 1-21 of each 28-day cycle, or (ii) is administered to the subject if the subject's eGFR is between 30 and 60 mL / min / 1.73 m. 2is orally administered to the subject at a dose of 10 mg on days 1 to 21 of each 28 day cycle, if the subject is older than 75 years of age or has a body mass index (BMI) of less than 18.5; and comprises dexamethasone, which is orally administered to the subject at (i) a dose of 40 mg on days 1, 8, 15, and 22 of each 28 day cycle, if the subject is older than 75 years of age or has a body mass index (BMI) of less than 18.5, if the subject is orally administered to the subject at a dose of 20 mg on days 1, 8, 15, and 22 of each 28 day cycle.

[0110] In some embodiments, the method comprises administering to the subject belantamab mafodotin, where the belantamab mafodotin is administered intravenously to the subject on day 1 of every 2 cycles at a dose of 1.9 mg / kg for 8 induction treatment cycles, each induction treatment cycle being 21 days; and administering bortezomib, where the bortezomib is administered intravenously to the subject at a dose of 1.3 mg / m for 8 induction treatment cycles. 2 administered subcutaneously (SC) to the subject on days 1, 4, 8, and 11 of every 21-day cycle at a dose of 25 mg for eight induction treatment cycles; or administering lenalidomide orally to the subject on each of days 1-14 of each 21-day cycle at a dose of 25 mg for eight induction treatment cycles; or (ii) administering to the subject an eGFR of 30-60 mL / min / 1.73 m 2orally administered to the subject at a dose of 10 mg on each of days 1 to 14 of each 21-day cycle, for eight induction treatment cycles; wherein dexamethasone is (i) orally administered to the subject at a dose of 20 mg on days 1, 2, 4, 5, 8, 9, 11, and 12 of each 21-day cycle, for eight induction treatment cycles, or (ii) orally administered to the subject at a dose of 10 mg on days 1, 2, 4, 5, 8, 9, 11, and 12 of each 21-day cycle, for eight induction treatment cycles, if the subject is older than 75 years of age or has a body mass index (BMI) less than 18.5, for eight induction treatment cycles. orally administered to the subject on days 8, 9, 11, and 12 of each induction treatment cycle; further comprising administering a maintenance therapy to the subject after the eight induction treatment cycles, the maintenance therapy comprising belantamab mafodotin, which is administered intravenously to the subject at a dose of 1.9 mg / kg on day 1 of every two cycles starting with cycle 9, each cycle being 28 days long; and comprising lenalidomide, which (i) is administered orally to the subject at a dose of 25 mg on each of days 1-21 of each 28-day cycle, or (ii) is administered to the subject if the subject's eGFR is between 30 and 60 mL / min / 1.73 m. 2 is orally administered to the subject at a dose of 10 mg on days 1 to 21 of each 28 day cycle, if the subject is older than 75 years of age or has a body mass index (BMI) of less than 18.5; and comprises dexamethasone, which is orally administered to the subject at (i) a dose of 40 mg on days 1, 8, 15, and 22 of each 28 day cycle, if the subject is older than 75 years of age or has a body mass index (BMI) of less than 18.5, if the subject is orally administered to the subject at a dose of 20 mg on days 1, 8, 15, and 22 of each 28 day cycle.

[0111] In some embodiments, the method comprises administering to the subject belantamab mafodotin, where the belantamab mafodotin is administered intravenously to the subject at a dose of 1.0 mg / kg on day 1 of each cycle for eight induction treatment cycles, where each induction treatment cycle is 21 days; and administering bortezomib, where the bortezomib is administered at a dose of 1.3 mg / m 2 administered subcutaneously (SC) to the subject on days 1, 4, 8, and 11 of every 21-day cycle at a dose of 25 mg for eight induction treatment cycles; or administering lenalidomide orally to the subject on each of days 1-14 of each 21-day cycle at a dose of 25 mg for eight induction treatment cycles; or (ii) administering to the subject an eGFR of 30-60 mL / min / 1.73 m 2 orally administered to the subject at a dose of 10 mg on each of days 1-14 of each 21-day cycle, for eight induction treatment cycles; wherein dexamethasone is (i) orally administered to the subject at a dose of 20 mg on days 1, 2, 4, 5, 8, 9, 11, and 12 of each 21-day cycle, for eight induction treatment cycles, or (ii) orally administered to the subject at a dose of 10 mg on days 1, 2, 4, 5, 8, 9, 11, and 12 of each 21-day cycle, for eight induction treatment cycles, if the subject is older than 75 years of age or has a body mass index (BMI) less than 18.5, for eight induction treatment cycles. orally administered to the subject on days 5, 8, 9, 11, and 12 of each induction treatment cycle; further comprising administering a maintenance therapy to the subject after the eight induction treatment cycles, the maintenance therapy comprising belantamab mafodotin, wherein belantamab mafodotin is administered intravenously to the subject on day 1 of each cycle at a dose of 1.0 mg / kg starting with cycle 9, each cycle being 28 days long; and comprising lenalidomide, wherein lenalidomide (i) is administered orally to the subject on each of days 1-21 of each 28-day cycle at a dose of 25 mg, or (ii) the subject's eGFR is between 30 and 60 mL / min / 1.73 m. 2is orally administered to the subject at a dose of 10 mg on days 1 to 21 of each 28 day cycle, if the subject is older than 75 years of age or has a body mass index (BMI) of less than 18.5; and comprises dexamethasone, which is orally administered to the subject at (i) a dose of 40 mg on days 1, 8, 15, and 22 of each 28 day cycle, if the subject is older than 75 years of age or has a body mass index (BMI) of less than 18.5, if the subject is orally administered to the subject at a dose of 20 mg on days 1, 8, 15, and 22 of each 28 day cycle.

[0112] In some embodiments, the method comprises administering to the subject belantamab mafodotin, where the belantamab mafodotin is administered intravenously to the subject on day 1 of each cycle at a dose of 1.4 mg / kg for eight induction treatment cycles, where each induction treatment cycle is 21 days; and administering bortezomib, where the bortezomib is administered at a dose of 1.3 mg / m for eight induction treatment cycles. 2 administered subcutaneously (SC) to the subject on days 1, 4, 8, and 11 of every 21-day cycle at a dose of 25 mg for eight induction treatment cycles; or administering lenalidomide orally to the subject on each of days 1-14 of each 21-day cycle at a dose of 25 mg for eight induction treatment cycles; or (ii) administering to the subject an eGFR of 30-60 mL / min / 1.73 m 2orally administered to the subject at a dose of 10 mg on each of days 1-14 of each 21-day cycle, for eight induction treatment cycles; wherein dexamethasone is (i) orally administered to the subject at a dose of 20 mg on days 1, 2, 4, 5, 8, 9, 11, and 12 of each 21-day cycle, for eight induction treatment cycles, or (ii) orally administered to the subject at a dose of 10 mg on days 1, 2, 4, 5, 8, 9, 11, and 12 of each 21-day cycle, for eight induction treatment cycles, if the subject is older than 75 years of age or has a body mass index (BMI) less than 18.5, for eight induction treatment cycles. orally administered to the subject on days 5, 8, 9, 11, and 12 of each induction treatment cycle; further comprising administering a maintenance therapy to the subject after the eight induction treatment cycles, the maintenance therapy comprising belantamab mafodotin, wherein belantamab mafodotin is administered intravenously to the subject on day 1 of each cycle at a dose of 1.4 mg / kg starting with cycle 9, each cycle being 28 days long; and comprising lenalidomide, wherein lenalidomide (i) is administered orally to the subject on each of days 1-21 of each 28-day cycle at a dose of 25 mg, or (ii) the subject's eGFR is between 30 and 60 mL / min / 1.73 m. 2 is orally administered to the subject at a dose of 10 mg on days 1 to 21 of each 28 day cycle, if the subject is older than 75 years of age or has a body mass index (BMI) of less than 18.5; and comprises dexamethasone, which is orally administered to the subject at (i) a dose of 40 mg on days 1, 8, 15, and 22 of each 28 day cycle, if the subject is older than 75 years of age or has a body mass index (BMI) of less than 18.5, if the subject is orally administered to the subject at a dose of 20 mg on days 1, 8, 15, and 22 of each 28 day cycle.

[0113] In some embodiments, the method comprises administering belantamab mafodotin to the subject, wherein belantamab mafodotin is administered intravenously to the subject at a dose of 1.4 mg / kg on day 1 of cycle 1 and at a dose of 1.0 mg / kg on day 1 of cycles 4 and 7, each treatment cycle being 21 days of induction treatment, and thereafter, starting with cycle 9, belantamab mafodotin is administered intravenously to the subject at a dose of 1.0 mg / kg on day 1 of every third cycle, each treatment cycle being 28 days of maintenance treatment. In some embodiments, the method comprises administering belantamab mafodotin to the subject, where the belantamab mafodotin is administered intravenously to the subject at a dose of 1.4 mg / kg on day 1 of each cycle for eight induction treatment cycles, and, beginning with cycle 4, at a dose of 1.0 mg / kg on day 1 of every third cycle, where each induction treatment cycle is 21 days; and administering bortezomib, where the bortezomib is administered intravenously to the subject at a dose of 1.3 mg / m for eight induction treatment cycles. 2 administered subcutaneously (SC) to the subject on days 1, 4, 8, and 11 of every 21-day cycle at a dose of 25 mg for eight induction treatment cycles; or administering lenalidomide orally to the subject on each of days 1-14 of each 21-day cycle at a dose of 25 mg for eight induction treatment cycles; or (ii) administering to the subject an eGFR of 30-60 mL / min / 1.73 m 2orally administered to the subject at a dose of 10 mg on each of days 1 to 14 of each 21-day cycle, for eight induction treatment cycles; wherein dexamethasone is (i) orally administered to the subject at a dose of 20 mg on days 1, 2, 4, 5, 8, 9, 11, and 12 of each 21-day cycle, for eight induction treatment cycles, or (ii) orally administered to the subject at a dose of 10 mg on days 1, 2, 4, 5, 8, 9, 11, and 12 of each 21-day cycle, for eight induction treatment cycles, if the subject is older than 75 years of age or has a body mass index (BMI) less than 18.5, for eight induction treatment cycles. orally administered to the subject on days 8, 9, 11, and 12 of each induction treatment cycle; further comprising administering a maintenance therapy to the subject after the eight induction treatment cycles, the maintenance therapy comprising belantamab mafodotin, wherein belantamab mafodotin is administered intravenously to the subject at a dose of 1.0 mg / kg on day 1 of every three cycles beginning with cycle 9, each cycle being 28 days long; and comprising lenalidomide, wherein lenalidomide (i) is administered orally to the subject at a dose of 25 mg on each of days 1-21 of each 28-day cycle, or (ii) the subject's eGFR is between 30 and 60 mL / min / 1.73 m. 2 is orally administered to the subject at a dose of 10 mg on days 1 to 21 of each 28 day cycle, if the subject is older than 75 years of age or has a body mass index (BMI) of less than 18.5; and comprises dexamethasone, which is orally administered to the subject at (i) a dose of 40 mg on days 1, 8, 15, and 22 of each 28 day cycle, if the subject is older than 75 years of age or has a body mass index (BMI) of less than 18.5, if the subject is orally administered to the subject at a dose of 20 mg on days 1, 8, 15, and 22 of each 28 day cycle.

[0114] In some embodiments, the method comprises administering belantamab mafodotin to the subject, wherein belantamab mafodotin is administered intravenously to the subject at a dose of 1.9 mg / kg on day 1 of cycle 1 and at a dose of 1.4 mg / kg on days 1 of cycles 4 and 7, each treatment cycle being 21 days of induction treatment, and thereafter, starting with cycle 9, belantamab mafodotin is administered intravenously to the subject at a dose of 1.4 mg / kg on day 1 of every third cycle, each treatment cycle being 28 days of maintenance treatment. In some embodiments, the method comprises administering belantamab mafodotin to the subject, where the belantamab mafodotin is administered intravenously to the subject at a dose of 1.9 mg / kg on day 1 of cycle 1, and starting with cycle 4, at a dose of 1.4 mg / kg on day 1 of every third cycle, for eight induction cycles, each induction cycle being 21 days; and administering bortezomib, where the bortezomib is administered intravenously to the subject at a dose of 1.3 mg / m for eight induction cycles. 2 administered subcutaneously (SC) to the subject on days 1, 4, 8, and 11 of every 21-day cycle at a dose of 25 mg for eight induction treatment cycles; or administering lenalidomide orally to the subject on each of days 1-14 of each 21-day cycle at a dose of 25 mg for eight induction treatment cycles; or (ii) administering to the subject an eGFR of 30-60 mL / min / 1.73 m 2orally administered to the subject at a dose of 10 mg on each of days 1 to 14 of each 21-day cycle, for eight induction treatment cycles; wherein dexamethasone is (i) orally administered to the subject at a dose of 20 mg on days 1, 2, 4, 5, 8, 9, 11, and 12 of each 21-day cycle, for eight induction treatment cycles, or (ii) orally administered to the subject at a dose of 10 mg on days 1, 2, 4, 5, 8, 9, 11, and 12 of each 21-day cycle, for eight induction treatment cycles, if the subject is older than 75 years of age or has a body mass index (BMI) less than 18.5, for eight induction treatment cycles. orally administered to the subject on days 8, 9, 11, and 12 of each induction treatment cycle; further comprising administering a maintenance therapy to the subject after the eight induction treatment cycles, the maintenance therapy comprising belantamab mafodotin, wherein belantamab mafodotin is administered intravenously to the subject at a dose of 1.4 mg / kg on day 1 of every three cycles beginning with cycle 9, each cycle being 28 days long; and comprising lenalidomide, wherein lenalidomide (i) is administered orally to the subject at a dose of 25 mg on each of days 1-21 of each 28-day cycle, or (ii) the subject's eGFR is between 30 and 60 mL / min / 1.73 m. 2 is orally administered to the subject at a dose of 10 mg on days 1 to 21 of each 28 day cycle, if the subject is older than 75 years of age or has a body mass index (BMI) of less than 18.5; and comprises dexamethasone, which is orally administered to the subject at (i) a dose of 40 mg on days 1, 8, 15, and 22 of each 28 day cycle, if the subject is older than 75 years of age or has a body mass index (BMI) of less than 18.5, if the subject is orally administered to the subject at a dose of 20 mg on days 1, 8, 15, and 22 of each 28 day cycle.

[0115] In some embodiments, the method comprises administering belantamab mafodotin to the subject, wherein belantamab mafodotin is administered intravenously to the subject at a dose of 1.9 mg / kg on day 1 of cycles 1 and 4, then at a dose of 1.4 mg / kg on day 1 of cycle 7, each treatment cycle being 21 days as induction treatment, and then, starting with cycle 9, belantamab mafodotin is administered intravenously to the subject at a dose of 1.4 mg / kg on day 1 of every third cycle, each treatment cycle being 28 days as maintenance treatment. In some embodiments, the method comprises administering belantamab mafodotin to the subject, where the belantamab mafodotin is administered intravenously to the subject at a dose of 1.9 mg / kg on day 1 of cycles 1 and 4, for eight induction treatment cycles, and, beginning with cycle 7, at a dose of 1.4 mg / kg on day 1 of every third cycle, where each induction treatment cycle is 21 days; and administering bortezomib, where the bortezomib is administered intravenously to the subject at a dose of 1.3 mg / m for eight induction treatment cycles. 2 administered subcutaneously (SC) to the subject on days 1, 4, 8, and 11 of every 21-day cycle at a dose of 25 mg for eight induction treatment cycles; or administering lenalidomide orally to the subject on each of days 1-14 of each 21-day cycle at a dose of 25 mg for eight induction treatment cycles; or (ii) administering to the subject an eGFR of 30-60 mL / min / 1.73 m 2orally administered to the subject at a dose of 10 mg on each of days 1 to 14 of each 21-day cycle, for eight induction treatment cycles; wherein dexamethasone is (i) orally administered to the subject at a dose of 20 mg on days 1, 2, 4, 5, 8, 9, 11, and 12 of each 21-day cycle, for eight induction treatment cycles, or (ii) orally administered to the subject at a dose of 10 mg on days 1, 2, 4, 5, 8, 9, 11, and 12 of each 21-day cycle, for eight induction treatment cycles, if the subject is older than 75 years of age or has a body mass index (BMI) less than 18.5, for eight induction treatment cycles. orally administered to the subject on days 8, 9, 11, and 12 of each induction treatment cycle; further comprising administering a maintenance therapy to the subject after the eight induction treatment cycles, the maintenance therapy comprising belantamab mafodotin, wherein belantamab mafodotin is administered intravenously to the subject at a dose of 1.4 mg / kg on day 1 of every three cycles beginning with cycle 9, each cycle being 28 days long; and comprising lenalidomide, wherein lenalidomide (i) is administered orally to the subject at a dose of 25 mg on each of days 1-21 of each 28-day cycle, or (ii) the subject's eGFR is between 30 and 60 mL / min / 1.73 m. 2 is orally administered to the subject at a dose of 10 mg on days 1 to 21 of each 28 day cycle, if the subject is older than 75 years of age or has a body mass index (BMI) of less than 18.5; and comprises dexamethasone, which is orally administered to the subject at (i) a dose of 40 mg on days 1, 8, 15, and 22 of each 28 day cycle, if the subject is older than 75 years of age or has a body mass index (BMI) of less than 18.5, if the subject is orally administered to the subject at a dose of 20 mg on days 1, 8, 15, and 22 of each 28 day cycle.

[0116] In some embodiments, the method comprises administering belantamab mafodotin to the subject, wherein belantamab mafodotin is administered intravenously to the subject at a dose of 1.4 mg / kg on day 1 of cycles 1 and 3, then at a dose of 1.0 mg / kg on day 1 of cycle 6, each treatment cycle being 21 days as induction treatment, and then, starting with cycle 9, belantamab mafodotin is administered intravenously to the subject at a dose of 1.0 mg / kg on day 1 of every third cycle, each treatment cycle being 28 days as maintenance treatment. In some embodiments, the method comprises administering belantamab mafodotin to the subject, where the belantamab mafodotin is administered intravenously to the subject at a dose of 1.4 mg / kg on day 1 of cycles 1 and 3, for eight induction treatment cycles, and at a dose of 1.0 mg / kg on day 1 of every third cycle, starting with cycle 6, where each induction treatment cycle is 21 days; and administering bortezomib, where the bortezomib is administered intravenously to the subject at a dose of 1.3 mg / m for eight induction treatment cycles. 2 administered subcutaneously (SC) to the subject on days 1, 4, 8, and 11 of every 21-day cycle at a dose of 25 mg for eight induction treatment cycles; or administering lenalidomide orally to the subject on each of days 1-14 of each 21-day cycle at a dose of 25 mg for eight induction treatment cycles; or (ii) administering to the subject an eGFR of 30-60 mL / min / 1.73 m 2orally administered to the subject at a dose of 10 mg on each of days 1 to 14 of each 21-day cycle, for eight induction treatment cycles; wherein dexamethasone is (i) orally administered to the subject at a dose of 20 mg on days 1, 2, 4, 5, 8, 9, 11, and 12 of each 21-day cycle, for eight induction treatment cycles, or (ii) orally administered to the subject at a dose of 10 mg on days 1, 2, 4, 5, 8, 9, 11, and 12 of each 21-day cycle, for eight induction treatment cycles, if the subject is older than 75 years of age or has a body mass index (BMI) less than 18.5, for eight induction treatment cycles. orally administered to the subject on days 8, 9, 11, and 12 of each induction treatment cycle; further comprising administering a maintenance therapy to the subject after the eight induction treatment cycles, the maintenance therapy comprising belantamab mafodotin, wherein belantamab mafodotin is administered intravenously to the subject at a dose of 1.0 mg / kg on day 1 of every three cycles beginning with cycle 9, each cycle being 28 days long; and comprising lenalidomide, wherein lenalidomide (i) is administered orally to the subject at a dose of 25 mg on each of days 1-21 of each 28-day cycle, or (ii) the subject's eGFR is between 30 and 60 mL / min / 1.73 m. 2 is orally administered to the subject at a dose of 10 mg on days 1 to 21 of each 28 day cycle, if the subject is older than 75 years of age or has a body mass index (BMI) of less than 18.5; and comprises dexamethasone, which is orally administered to the subject at (i) a dose of 40 mg on days 1, 8, 15, and 22 of each 28 day cycle, if the subject is older than 75 years of age or has a body mass index (BMI) of less than 18.5, if the subject is orally administered to the subject at a dose of 20 mg on days 1, 8, 15, and 22 of each 28 day cycle.

[0117] In some embodiments, the method comprises administering belantamab mafodotin to the subject, where belantamab mafodotin is administered intravenously to the subject at a dose of 1.0 mg / kg on day 1 of cycle 1 and cycle 5, each treatment cycle being 21 days as an induction treatment, and then, starting with cycle 9, administering belantamab mafodotin to the subject intravenously at a dose of 1.0 mg / kg on day 1 of every third cycle, each treatment cycle being 28 days as a maintenance treatment. In some embodiments, the method comprises administering belantamab mafodotin to the subject, where belantamab mafodotin is administered intravenously to the subject at a dose of 1.0 mg / kg on day 1 of cycle 1 and cycle 5, for eight induction treatment cycles, each induction treatment cycle being 21 days; and administering bortezomib, where bortezomib is administered intravenously to the subject at a dose of 1.3 mg / m for eight induction treatment cycles. 2 administered subcutaneously (SC) to the subject on days 1, 4, 8, and 11 of every 21-day cycle at a dose of 25 mg for eight induction treatment cycles; or administering lenalidomide orally to the subject on each of days 1-14 of each 21-day cycle at a dose of 25 mg for eight induction treatment cycles; or (ii) administering to the subject an eGFR of 30-60 mL / min / 1.73 m 2orally administered to the subject at a dose of 10 mg on each of days 1 to 14 of each 21-day cycle, for eight induction treatment cycles; wherein dexamethasone is (i) orally administered to the subject at a dose of 20 mg on days 1, 2, 4, 5, 8, 9, 11, and 12 of each 21-day cycle, for eight induction treatment cycles, or (ii) orally administered to the subject at a dose of 10 mg on days 1, 2, 4, 5, 8, 9, 11, and 12 of each 21-day cycle, for eight induction treatment cycles, if the subject is older than 75 years of age or has a body mass index (BMI) less than 18.5, for eight induction treatment cycles. orally administered to the subject on days 8, 9, 11, and 12 of each induction treatment cycle; further comprising administering a maintenance therapy to the subject after the eight induction treatment cycles, the maintenance therapy comprising belantamab mafodotin, wherein belantamab mafodotin is administered intravenously to the subject at a dose of 1.0 mg / kg on day 1 of every three cycles beginning with cycle 9, each cycle being 28 days long; and comprising lenalidomide, wherein lenalidomide (i) is administered orally to the subject at a dose of 25 mg on each of days 1-21 of each 28-day cycle, or (ii) the subject's eGFR is between 30 and 60 mL / min / 1.73 m. 2 is orally administered to the subject at a dose of 10 mg on days 1 to 21 of each 28 day cycle, if the subject is older than 75 years of age or has a body mass index (BMI) of less than 18.5; and comprises dexamethasone, which is orally administered to the subject at (i) a dose of 40 mg on days 1, 8, 15, and 22 of each 28 day cycle, if the subject is older than 75 years of age or has a body mass index (BMI) of less than 18.5, if the subject is orally administered to the subject at a dose of 20 mg on days 1, 8, 15, and 22 of each 28 day cycle.

[0118] The present disclosure also provides the use of (a) a therapeutically effective amount of an anti-BCMA antigen binding protein; (b) a therapeutically effective amount of a proteasome inhibitor; (c) a therapeutically effective amount of an immunomodulatory imide drug; and (d) a therapeutically effective amount of a corticosteroid in the manufacture of a medicament for use in treating multiple myeloma in a subject. The present disclosure also provides (a) a therapeutically effective amount of an anti-BCMA antigen binding protein; (b) a therapeutically effective amount of a proteasome inhibitor; (c) a therapeutically effective amount of an immunomodulatory imide drug; and (d) a therapeutically effective amount of a corticosteroid for use in treating multiple myeloma in a subject. In some embodiments, the subject is newly diagnosed with multiple myeloma. In some of these embodiments, the subject is ineligible for autologous stem cell transplantation.

[0119] In some embodiments, the anti-BCMA antigen binding protein is belantamab mafodotin, and the belantamab mafodotin is formulated for administration to a subject according to a schedule selected from the group consisting of: (i) belantamab mafodotin at a dose of 1.9 mg / kg administered on day 1 of each cycle for 8 induction treatment cycles, where each induction treatment cycle is 21 days long; (ii) belantamab mafodotin at a dose of 1.4 mg / kg administered on day 1 of every 2nd cycle for 8 induction treatment cycles. (iii) belantamab mafodotin at a dose of 1.9 mg / kg is administered on day 1 of every 2 cycles for 8 induction cycles, where each induction cycle is 21 days; (iv) belantamab mafodotin at a dose of 1.0 mg / kg is administered on day 1 of every cycle for 8 induction cycles, where each induction cycle is 21 days; (v) belantamab mafodotin at a dose of 1.4 mg / kg is administered on day 1 of every 2 induction cycles, where each induction cycle is 21 days; (vi) for eight induction cycles, belantamab mafodotin at a dose of 1.4 mg / kg is administered on day 1 of cycle 1, and from cycle 4, belantamab mafodotin at a dose of 1.0 mg / kg is administered on day 1 of every third cycle, and each induction cycle is 21 days long; (vii) for eight induction cycles, belantamab mafodotin at a dose of 1.9 mg / kg is administered on day 1 of cycle 1, and from cycle 4, belantamab mafodotin at a dose of 1.9 mg / kg is administered on day 1 of cycle 1, and (viii) for eight induction cycles, belantamab mafodotin at a dose of 1.9 mg / kg is administered on day 1 of cycles 1 and 4, and from cycle 7, belantamab mafodotin at a dose of 1.4 mg / kg is administered on day 1 of every three cycles, where each induction cycle is 21 days; (ix) for eight induction cycles, belantamab mafodotin at a dose of 1.(x) for eight induction cycles, belantamab mafodotin at a dose of 1.0 mg / kg is administered on day 1 of cycles 1 and 3, and from cycle 6, belantamab mafodotin at a dose of 1.0 mg / kg is administered on day 1 of every third cycle, where each induction cycle is 21 days; (x) for eight induction cycles, belantamab mafodotin at a dose of 1.0 mg / kg is administered on day 1 of cycles 1 and 5, where each induction cycle is 21 days; the proteasome inhibitor is bortezomib, and for eight induction cycles, the bortezomib is 1.3 mg / m. 2 and (ii) the subject has an eGFR of 30-60 mL / min / 1.73 m; the immunomodulatory imide drug is lenalidomide, which is formulated for oral administration to the subject on each of days 1-14 of each 21-day cycle at a dose of 25 mg for eight induction treatment cycles; or (iii) the subject has an eGFR of 30-60 mL / min / 1.73 m. 2 is orally administered to the subject at a dose of 10 mg on each of days 1-14 of each 21-day cycle, for eight induction treatment cycles; the corticosteroid is dexamethasone, which is formulated for oral administration to the subject (i) at a dose of 20 mg on days 1, 2, 4, 5, 8, 9, 11, and 12 of each 21-day cycle, for eight induction treatment cycles, or (ii) at a dose of 10 mg on days 1, 2, 4, 5, 8, 9, 11, and 12 of each 21-day cycle, for eight induction treatment cycles, if the subject is older than 75 years of age or has a body mass index (BMI) less than 18.5.

[0120] In some embodiments, the use further comprises a maintenance therapy for administration to the subject after the eight induction treatment cycles, the maintenance therapy comprising: (a) a therapeutically effective amount of an anti-BCMA antigen binding protein; (b) a therapeutically effective amount of an immunomodulatory imido drug; and (c) a therapeutically effective amount of a corticosteroid. In some embodiments, the maintenance therapy does not comprise a proteasome inhibitor. In some embodiments, the maintenance therapy does not comprise bortezomib.

[0121] In some embodiments of the maintenance therapy, the anti-BCMA antigen binding protein is belantamab mafodotin, and the belantamab mafodotin is formulated for intravenous administration according to a schedule selected from the group consisting of: (i) administered on day 1 of every 28-day cycle; (ii) administered on day 1 of every two 28-day cycles; and (iii) administered on day 1 of every three 28-day cycles; and the immunomodulatory imide drug is lenalidomide, and the lenalidomide is administered (i) at a dose of 25 mg on each of days 1-21 of each 28-day cycle, or (ii) when the subject's eGFR is between 30 and 60 mL / min / 1.73 m 2 is formulated for oral administration to a subject at a dose of 10 mg on days 1 to 21 of each 28 day cycle; and the corticosteroid is dexamethasone, which is formulated for oral administration to a subject (i) at a dose of 40 mg on days 1, 8, 15, and 22 of each 28 day cycle, or (ii) at a dose of 20 mg on days 1, 8, 15, and 22 of each 28 day cycle, if the subject is older than 75 years of age or has a body mass index (BMI) less than 18.5.

[0122] In some embodiments, the induction treatment comprises belantamab mafodotin, the belantamab mafodotin formulated for intravenous administration to a subject on day 1 of each cycle at a dose of 1.9 mg / kg for eight induction treatment cycles, each induction treatment cycle being 21 days long; and bortezomib, the bortezomib formulated for intravenous administration to a subject on day 1 of each cycle at a dose of 1.3 mg / kg for eight induction treatment cycles. 2on days 1, 4, 8, and 11 of every 21-day cycle; comprising lenalidomide, which is (i) formulated for oral administration to a subject at a dose of 25 mg on each of days 1-14 of each 21-day cycle for eight induction treatment cycles, or (ii) a subject with an eGFR of 30-60 mL / min / 1.73 m 2 and comprising dexamethasone, wherein the dexamethasone is (i) formulated for oral administration to a subject at a dose of 20 mg on days 1, 2, 4, 5, 8, 9, 11, and 12 of each 21-day cycle, for eight induction treatment cycles, or (ii) formulated for oral administration to a subject at a dose of 10 mg on days 1, 2, 4, 5, 8, 9, 11, and 12 of each 21-day cycle, if the subject is older than 75 years of age or has a body mass index (BMI) of less than 18.5, for eight induction treatment cycles. the maintenance therapy comprises belantamab mafodotin, the belantamab mafodotin being formulated for intravenous administration to a subject on days 1, 2, 4, 5, 8, 9, 11, and 12 of each 21-day cycle, at a dose of 1.9 mg / kg, beginning with cycle 9, and comprising lenalidomide, the lenalidomide being administered intravenously to a subject on day 1 of each cycle, the cycle being 28 days long, at (i) a dose of 25 mg, the lenalidomide being administered intravenously to a subject on each of days 1-21 of each 28-day cycle, or (ii) if the subject's eGFR is between 30 and 60 mL / min / 1.73 m 2 is formulated for oral administration to a subject at a dose of 10 mg on days 1 to 21 of each 28 day cycle; and comprising dexamethasone, which is formulated for oral administration to a subject (i) at a dose of 40 mg on days 1, 8, 15, and 22 of each 28 day cycle, or (ii) at a dose of 20 mg on days 1, 8, 15, and 22 of each 28 day cycle, if the subject is older than 75 years of age or has a body mass index (BMI) of less than 18.5.

[0123] In some embodiments, the induction treatment comprises belantamab mafodotin, the belantamab mafodotin formulated for intravenous administration to a subject on day 1 of every 2 cycles at a dose of 1.4 mg / kg for 8 induction treatment cycles, each induction treatment cycle being 21 days long; and comprises bortezomib, the bortezomib formulated for intravenous administration to a subject on day 1 of every 2 cycles at a dose of 1.3 mg / kg for 8 induction treatment cycles. 2 on days 1, 4, 8, and 11 of every 21-day cycle; comprising lenalidomide, which is (i) formulated for oral administration to a subject at a dose of 25 mg on each of days 1-14 of each 21-day cycle for eight induction treatment cycles, or (ii) a subject with an eGFR of 30-60 mL / min / 1.73 m 2 and comprising dexamethasone, wherein the dexamethasone is (i) formulated for oral administration to a subject at a dose of 20 mg on days 1, 2, 4, 5, 8, 9, 11, and 12 of each 21-day cycle, for eight induction treatment cycles, or (ii) formulated for oral administration to a subject at a dose of 10 mg on days 1, 2, 4, 5, 8, 9, 11, and 12 of each 21-day cycle, if the subject is older than 75 years of age or has a body mass index (BMI) of less than 18.5, for eight induction treatment cycles. the maintenance therapy comprises belantamab mafodotin, the belantamab mafodotin being formulated for intravenous administration to a subject on days 1, 2, 4, 5, 8, 9, 11, and 12 of each 21-day cycle, at a dose of 1.4 mg / kg, beginning with cycle 9, on day 1 of every 2 cycles, each cycle being 28 days long; and the maintenance therapy comprises lenalidomide, the lenalidomide being administered (i) at a dose of 25 mg on each of days 1-21 of each 28-day cycle, or (ii) if the subject's eGFR is between 30 and 60 mL / min / 1.73 m 2is formulated for oral administration to a subject at a dose of 10 mg on days 1 to 21 of each 28 day cycle; and comprising dexamethasone, which is formulated for oral administration to a subject (i) at a dose of 40 mg on days 1, 8, 15, and 22 of each 28 day cycle, or (ii) at a dose of 20 mg on days 1, 8, 15, and 22 of each 28 day cycle, if the subject is older than 75 years of age or has a body mass index (BMI) of less than 18.5.

[0124] In some embodiments, the induction treatment comprises belantamab mafodotin, the belantamab mafodotin formulated for intravenous administration to a subject on day 1 of every 2 cycles at a dose of 1.9 mg / kg for 8 induction treatment cycles, each induction treatment cycle being 21 days long; and bortezomib, the bortezomib formulated for intravenous administration to a subject on day 1 of every 2 cycles at a dose of 1.3 mg / kg for 8 induction treatment cycles. 2 on days 1, 4, 8, and 11 of every 21-day cycle; comprising lenalidomide, which is (i) formulated for oral administration to a subject at a dose of 25 mg on each of days 1-14 of each 21-day cycle for eight induction treatment cycles, or (ii) a subject with an eGFR of 30-60 mL / min / 1.73 m 2and comprising dexamethasone, wherein the dexamethasone is (i) formulated for oral administration to a subject at a dose of 20 mg on days 1, 2, 4, 5, 8, 9, 11, and 12 of each 21-day cycle, for eight induction treatment cycles, or (ii) formulated for oral administration to a subject at a dose of 10 mg on days 1, 2, 4, 5, 8, 9, 11, and 12 of each 21-day cycle, if the subject is older than 75 years of age or has a body mass index (BMI) of less than 18.5, for eight induction treatment cycles. the maintenance therapy comprises belantamab mafodotin, the belantamab mafodotin being formulated for intravenous administration to a subject on days 1, 2, 4, 5, 8, 9, 11, and 12 of each 21-day cycle, at a dose of 1.9 mg / kg, on day 1 of every 2 cycles beginning with cycle 9, each cycle being 28 days long; and the maintenance therapy comprises lenalidomide, the lenalidomide being administered (i) at a dose of 25 mg on each of days 1-21 of each 28-day cycle, or (ii) if the subject has an eGFR of 30-60 mL / min / 1.73 m 2 is formulated for oral administration to a subject at a dose of 10 mg on days 1 to 21 of each 28 day cycle; and comprising dexamethasone, which is formulated for oral administration to a subject (i) at a dose of 40 mg on days 1, 8, 15, and 22 of each 28 day cycle, or (ii) at a dose of 20 mg on days 1, 8, 15, and 22 of each 28 day cycle, if the subject is older than 75 years of age or has a body mass index (BMI) of less than 18.5.

[0125] In some embodiments, the induction treatment comprises belantamab mafodotin, the belantamab mafodotin formulated for intravenous administration to a subject on day 1 of each cycle at a dose of 1.0 mg / kg for eight induction treatment cycles, each induction treatment cycle being 21 days long; and comprises bortezomib, the bortezomib formulated for intravenous administration to a subject on day 1 of each cycle at a dose of 1.3 mg / kg for eight induction treatment cycles. 2 on days 1, 4, 8, and 11 of every 21-day cycle; comprising lenalidomide, which is (i) formulated for oral administration to a subject at a dose of 25 mg on each of days 1-14 of each 21-day cycle for eight induction treatment cycles, or (ii) a subject with an eGFR of 30-60 mL / min / 1.73 m 2 and comprising dexamethasone, wherein the dexamethasone is (i) formulated for oral administration to a subject at a dose of 20 mg on days 1, 2, 4, 5, 8, 9, 11, and 12 of each 21-day cycle, for eight induction treatment cycles, or (ii) formulated for oral administration to a subject at a dose of 10 mg on days 1, 2, 4, 5, 8, 9, 11, and 12 of each 21-day cycle, if the subject is older than 75 years of age or has a body mass index (BMI) of less than 18.5, for eight induction treatment cycles. the maintenance therapy comprises belantamab mafodotin, the belantamab mafodotin being formulated for intravenous administration to a subject on days 1, 2, 4, 5, 8, 9, 11, and 12 of each 21-day cycle, at a dose of 1.0 mg / kg, beginning with cycle 9, and wherein each cycle is 28 days long; and the maintenance therapy comprises lenalidomide, the lenalidomide being administered (i) at a dose of 25 mg on each of days 1-21 of each 28-day cycle, or (ii) when the subject's eGFR is between 30 and 60 mL / min / 1.73 m 2is formulated for oral administration to a subject at a dose of 10 mg on days 1 to 21 of each 28 day cycle; and comprising dexamethasone, which is formulated for oral administration to a subject (i) at a dose of 40 mg on days 1, 8, 15, and 22 of each 28 day cycle, or (ii) at a dose of 20 mg on days 1, 8, 15, and 22 of each 28 day cycle, if the subject is older than 75 years of age or has a body mass index (BMI) of less than 18.5.

[0126] In some embodiments, the induction treatment comprises belantamab mafodotin, the belantamab mafodotin formulated for intravenous administration to a subject on day 1 of each cycle at a dose of 1.4 mg / kg for eight induction treatment cycles, each induction treatment cycle being 21 days long; and comprises bortezomib, the bortezomib formulated for intravenous administration to a subject on day 1 of each cycle at a dose of 1.3 mg / kg for eight induction treatment cycles. 2 on days 1, 4, 8, and 11 of every 21-day cycle; comprising lenalidomide, which is (i) formulated for oral administration to a subject at a dose of 25 mg on each of days 1-14 of each 21-day cycle for eight induction treatment cycles, or (ii) a subject with an eGFR of 30-60 mL / min / 1.73 m 2and comprising dexamethasone, wherein the dexamethasone is (i) formulated for oral administration to a subject at a dose of 20 mg on days 1, 2, 4, 5, 8, 9, 11, and 12 of each 21-day cycle, for eight induction treatment cycles, or (ii) formulated for oral administration to a subject at a dose of 10 mg on days 2, 3, 4, 5, 8, 9, 11, and 12 of each 21-day cycle, for eight induction treatment cycles, if the subject is older than 75 years of age or has a body mass index (BMI) less than 18.5, for eight induction treatment cycles. the maintenance therapy comprises belantamab mafodotin, the belantamab mafodotin being formulated for oral administration to a subject on days 1, 2, 4, 5, 8, 9, 11, and 12 of a 1-day cycle; further comprising belantamab mafodotin, the belantamab mafodotin being formulated for intravenous administration to a subject on day 1 of each cycle beginning with cycle 9, the cycle being 28 days long; and comprising lenalidomide, the lenalidomide being administered (i) at a dose of 25 mg on each of days 1-21 of each 28-day cycle, or (ii) when the subject's eGFR is between 30 and 60 mL / min / 1.73 m 2 is formulated for oral administration to a subject at a dose of 10 mg on days 1 to 21 of each 28 day cycle; and comprising dexamethasone, which is formulated for oral administration to a subject (i) at a dose of 40 mg on days 1, 8, 15, and 22 of each 28 day cycle, or (ii) at a dose of 20 mg on days 1, 8, 15, and 22 of each 28 day cycle, if the subject is older than 75 years of age or has a body mass index (BMI) of less than 18.5.

[0127] In some embodiments, the induction treatment comprises belantamab mafodotin, the belantamab mafodotin being formulated for intravenous administration to a subject at a dose of 1.4 mg / kg on day 1 of cycle 1 and, beginning with cycle 4, at a dose of 1.0 mg / kg on day 1 of every third cycle, for eight induction treatment cycles, each induction treatment cycle being 21 days; and comprises bortezomib, the bortezomib being formulated for intravenous administration to a subject at a dose of 1.3 mg / kg on day 1 of cycle 1 and, beginning with cycle 4, at a dose of 1.0 mg / kg on day 1 of every third cycle, for eight induction treatment cycles, each induction treatment cycle being 21 days; 2 and (ii) a subject with an eGFR of 30-60 mL / min / 1.73 m2 or more; 2 and comprising dexamethasone, wherein the dexamethasone is (i) formulated for oral administration to a subject at a dose of 20 mg on days 1, 2, 4, 5, 8, 9, 11, and 12 of each 21-day cycle, for eight induction treatment cycles, or (ii) formulated for oral administration to a subject at a dose of 10 mg on days 1, 2, 4, 5, 8, 9, 11, and 12 of each 21-day cycle, if the subject is older than 75 years of age or has a body mass index (BMI) of less than 18.5, for eight induction treatment cycles. the maintenance therapy comprises belantamab mafodotin, the belantamab mafodotin being formulated for intravenous administration to a subject on days 1, 2, 4, 5, 8, 9, 11, and 12 of each 21-day cycle, at a dose of 1.0 mg / kg, on day 1 of every 3 cycles beginning with cycle 9, each cycle being 28 days long; and the maintenance therapy comprises lenalidomide, the lenalidomide being administered (i) at a dose of 25 mg on each of days 1-21 of each 28-day cycle, or (ii) if the subject has an eGFR of 30-60 mL / min / 1.73 m 2is formulated for oral administration to a subject at a dose of 10 mg on days 1 to 21 of each 28 day cycle; and comprising dexamethasone, which is formulated for oral administration to a subject (i) at a dose of 40 mg on days 1, 8, 15, and 22 of each 28 day cycle, or (ii) at a dose of 20 mg on days 1, 8, 15, and 22 of each 28 day cycle, if the subject is older than 75 years of age or has a body mass index (BMI) of less than 18.5.

[0128] In some embodiments, the induction treatment comprises belantamab mafodotin, the belantamab mafodotin being formulated for intravenous administration to a subject at a dose of 1.9 mg / kg on day 1 of cycle 1 and, beginning with cycle 4, at a dose of 1.4 mg / kg on day 1 of every third cycle, for eight induction treatment cycles, each induction treatment cycle being 21 days; and comprises bortezomib, the bortezomib being formulated for intravenous administration to a subject at a dose of 1.3 mg / kg on day 1 of cycle 1 and, beginning with cycle 4, at a dose of 1.4 mg / kg on day 1 of every third cycle, for eight induction treatment cycles, each induction treatment cycle being 21 days; 2 on days 1, 4, 8, and 11 of every 21-day cycle; comprising lenalidomide, which is (i) formulated for oral administration to a subject at a dose of 25 mg on each of days 1-14 of each 21-day cycle for eight induction treatment cycles, or (ii) a subject with an eGFR of 30-60 mL / min / 1.73 m 2and comprising dexamethasone, wherein the dexamethasone is (i) formulated for oral administration to a subject at a dose of 20 mg on days 1, 2, 4, 5, 8, 9, 11, and 12 of each 21-day cycle, for eight induction treatment cycles, or (ii) formulated for oral administration to a subject at a dose of 10 mg on days 1, 2, 4, 5, 8, 9, 11, and 12 of each 21-day cycle, if the subject is older than 75 years of age or has a body mass index (BMI) of less than 18.5, for eight induction treatment cycles. the maintenance therapy comprises belantamab mafodotin, the belantamab mafodotin being formulated for intravenous administration to a subject on days 1, 2, 4, 5, 8, 9, 11, and 12 of each 21-day cycle, at a dose of 1.4 mg / kg, beginning with cycle 9, on day 1 of every 3 cycles, each cycle being 28 days long; and the maintenance therapy comprises lenalidomide, the lenalidomide being administered (i) at a dose of 25 mg on each of days 1-21 of each 28-day cycle, or (ii) if the subject's eGFR is between 30 and 60 mL / min / 1.73 m 2 is formulated for oral administration to a subject at a dose of 10 mg on days 1 to 21 of each 28 day cycle; and comprising dexamethasone, which is formulated for oral administration to a subject (i) at a dose of 40 mg on days 1, 8, 15, and 22 of each 28 day cycle, or (ii) at a dose of 20 mg on days 1, 8, 15, and 22 of each 28 day cycle, if the subject is older than 75 years of age or has a body mass index (BMI) of less than 18.5.

[0129] In some embodiments, the induction treatment comprises belantamab mafodotin, the belantamab mafodotin being formulated for intravenous administration to a subject at a dose of 1.9 mg / kg on day 1 of cycles 1 and 4, and starting with cycle 7, at a dose of 1.4 mg / kg on day 1 of every third cycle, for eight induction treatment cycles, each induction treatment cycle being 21 days; and comprises bortezomib, the bortezomib being formulated for intravenous administration to a subject at a dose of 1.3 mg / kg on day 1 of cycles 1 and 4, for eight induction treatment cycles, each induction treatment cycle being 21 days. 2 on days 1, 4, 8, and 11 of every 21-day cycle; comprising lenalidomide, which is (i) formulated for oral administration to a subject at a dose of 25 mg on each of days 1-14 of each 21-day cycle for eight induction treatment cycles, or (ii) a subject with an eGFR of 30-60 mL / min / 1.73 m 2 and comprising dexamethasone, wherein the dexamethasone is (i) formulated for oral administration to a subject at a dose of 20 mg on days 1, 2, 4, 5, 8, 9, 11, and 12 of each 21-day cycle, for eight induction treatment cycles, or (ii) formulated for oral administration to a subject at a dose of 10 mg on days 1, 2, 4, 5, 8, 9, 11, and 12 of each 21-day cycle, if the subject is older than 75 years of age or has a body mass index (BMI) of less than 18.5, for eight induction treatment cycles. the maintenance therapy comprises belantamab mafodotin, the belantamab mafodotin being formulated for intravenous administration to a subject on days 1, 2, 4, 5, 8, 9, 11, and 12 of each 21-day cycle, at a dose of 1.4 mg / kg, beginning with cycle 9, on day 1 of every 3 cycles, each cycle being 28 days long; and the maintenance therapy comprises lenalidomide, the lenalidomide being administered (i) at a dose of 25 mg on each of days 1-21 of each 28-day cycle, or (ii) if the subject's eGFR is between 30 and 60 mL / min / 1.73 m 2is formulated for oral administration to a subject at a dose of 10 mg on days 1 to 21 of each 28 day cycle; and comprising dexamethasone, which is formulated for oral administration to a subject (i) at a dose of 40 mg on days 1, 8, 15, and 22 of each 28 day cycle, or (ii) at a dose of 20 mg on days 1, 8, 15, and 22 of each 28 day cycle, if the subject is older than 75 years of age or has a body mass index (BMI) of less than 18.5.

[0130] In some embodiments, the induction treatment comprises belantamab mafodotin, the belantamab mafodotin being formulated for intravenous administration to a subject at a dose of 1.4 mg / kg on day 1 of cycles 1 and 3, and starting with cycle 6, at a dose of 1.0 mg / kg on day 1 of every third cycle, for eight induction treatment cycles, each induction treatment cycle being 21 days; and comprises bortezomib, the bortezomib being formulated for intravenous administration to a subject at a dose of 1.3 mg / kg on day 1 of cycles 1 and 3, for eight induction treatment cycles, each induction treatment cycle being 21 days. 2 on days 1, 4, 8, and 11 of every 21-day cycle; comprising lenalidomide, which is (i) formulated for oral administration to a subject at a dose of 25 mg on each of days 1-14 of each 21-day cycle for eight induction treatment cycles, or (ii) a subject with an eGFR of 30-60 mL / min / 1.73 m 2and comprising dexamethasone, wherein the dexamethasone is (i) formulated for oral administration to a subject at a dose of 20 mg on days 1, 2, 4, 5, 8, 9, 11, and 12 of each 21-day cycle, for eight induction treatment cycles, or (ii) formulated for oral administration to a subject at a dose of 10 mg on days 2, 3, 4, 5, 8, 9, 11, and 12 of each 21-day cycle, for eight induction treatment cycles, if the subject is older than 75 years of age or has a body mass index (BMI) less than 18.5, for eight induction treatment cycles. the maintenance therapy comprises belantamab mafodotin, the belantamab mafodotin being formulated for oral administration to a subject on days 1, 2, 4, 5, 8, 9, 11, and 12 of a one-day cycle; further comprising: belantamab mafodotin, the belantamab mafodotin being formulated for intravenous administration to a subject at a dose of 1.0 mg / kg on day 1 of every three cycles beginning with cycle 9, each cycle being 28 days long; and lenalidomide, the lenalidomide being administered (i) at a dose of 25 mg on each of days 1-21 of each 28-day cycle, or (ii) if the subject's eGFR is between 30 and 60 mL / min / 1.73 m. 2 is formulated for oral administration to a subject at a dose of 10 mg on days 1 to 21 of each 28 day cycle; and comprising dexamethasone, which is formulated for oral administration to a subject (i) at a dose of 40 mg on days 1, 8, 15, and 22 of each 28 day cycle, or (ii) at a dose of 20 mg on days 1, 8, 15, and 22 of each 28 day cycle, if the subject is older than 75 years of age or has a body mass index (BMI) of less than 18.5.

[0131] In some embodiments, the induction treatment comprises belantamab mafodotin, the belantamab mafodotin formulated for intravenous administration to a subject on days 1 of cycles 1 and 5 at a dose of 1.0 mg / kg for eight induction treatment cycles, each induction treatment cycle being 21 days long; and bortezomib, the bortezomib formulated for intravenous administration to a subject on days 1 of cycles 1 and 5 at a dose of 1.0 mg / kg for eight induction treatment cycles, each induction treatment cycle being 21 days long; 2 on days 1, 4, 8, and 11 of every 21-day cycle; comprising lenalidomide, which is (i) formulated for oral administration to a subject at a dose of 25 mg on each of days 1-14 of each 21-day cycle for eight induction treatment cycles, or (ii) a subject with an eGFR of 30-60 mL / min / 1.73 m 2 and comprising dexamethasone, wherein the dexamethasone is (i) formulated for oral administration to a subject at a dose of 20 mg on days 1, 2, 4, 5, 8, 9, 11, and 12 of each 21-day cycle, for eight induction treatment cycles, or (ii) formulated for oral administration to a subject at a dose of 10 mg on days 1, 2, 4, 5, 8, 9, 11, and 12 of each 21-day cycle, if the subject is older than 75 years of age or has a body mass index (BMI) of less than 18.5, for eight induction treatment cycles. the maintenance therapy comprises belantamab mafodotin, the belantamab mafodotin being formulated for intravenous administration to a subject on days 1, 2, 4, 5, 8, 9, 11, and 12 of each 21-day cycle, at a dose of 1.0 mg / kg, on day 1 of every 3 cycles beginning with cycle 9, each cycle being 28 days long; and the maintenance therapy comprises lenalidomide, the lenalidomide being administered (i) at a dose of 25 mg on each of days 1-21 of each 28-day cycle, or (ii) if the subject has an eGFR of 30-60 mL / min / 1.73 m 2is formulated for oral administration to a subject at a dose of 10 mg on days 1 to 21 of each 28 day cycle; and comprising dexamethasone, which is formulated for oral administration to a subject (i) at a dose of 40 mg on days 1, 8, 15, and 22 of each 28 day cycle, or (ii) at a dose of 20 mg on days 1, 8, 15, and 22 of each 28 day cycle, if the subject is older than 75 years of age or has a body mass index (BMI) of less than 18.5.

[0132] Example of a Dosing Schedule In some embodiments, the dosing schedule comprises induction treatment with belantamab mafodotin+VRd for a total of eight cycles, followed by maintenance treatment with belantamab mafodotin+two-drug Rd. In some embodiments, the dosing schedule comprises administration of belantamab mafodotin in combination with VRd for a total of eight induction treatment cycles, each cycle lasting 21 days, followed by administration of belantamab mafodotin in combination with Rd maintenance treatment for a total of eight cycles lasting 28 days.

[0133] Induction treatment (Q3W): Belantamab + mafodotin + VRd; up to cycle 8 Belantamab mafodotin is administered intravenously (IV) in combination with VRd on day 1 of every 21-day cycle, every two 21-day cycles, every three 21-day cycles, or every four 21-day cycles for the first eight (induction) cycles.

[0134] In some embodiments, the induction treatment comprises administering belantamab mafodotin at a dose of 1.9 mg / kg on day 1 of each cycle for eight induction treatment cycles, each cycle being 21 days long. In some embodiments, the induction treatment comprises administering belantamab mafodotin at a dose of 1.4 mg / kg on day 1 of every two cycles for eight induction treatment cycles, each cycle being 21 days long. In some embodiments, the induction treatment comprises administering belantamab mafodotin at a dose of 1.9 mg / kg on day 1 of every two cycles for eight induction treatment cycles, each cycle being 21 days long. In some embodiments, the induction treatment comprises administering belantamab mafodotin at a dose of 1.0 mg / kg on day 1 of each cycle for eight induction treatment cycles, each cycle being 21 days long. In some embodiments, the induction treatment comprises administering belantamab mafodotin at a dose of 1.4 mg / kg on day 1 of each cycle for eight induction treatment cycles, each cycle being 21 days long.

[0135] In some embodiments, the induction treatment comprises administering belantamab mafodotin at a dose of 1.4 mg / kg on day 1 of cycle 1, followed by a dose of 1.0 mg / kg on day 1 of cycles 4 and 7, each cycle being 21 days long. In some embodiments, the induction treatment comprises administering belantamab mafodotin at a dose of 1.9 mg / kg on day 1 of cycle 1, followed by a dose of 1.4 mg / kg on day 1 of cycles 4 and 7, each cycle being 21 days long.

[0136] In some embodiments, the induction treatment comprises administering belantamab mafodotin at a dose of 1.9 mg / kg on day 1 of cycle 1 and cycle 4, followed by a dose of 1.4 mg / kg on day 1 of cycle 7, each cycle being 21 days long. In some embodiments, the induction treatment comprises administering belantamab mafodotin at a dose of 1.4 mg / kg on day 1 of cycle 1 and cycle 3, followed by a dose of 1.0 mg / kg on day 1 of cycle 6, each cycle being 21 days long. In some embodiments, the induction treatment comprises administering belantamab mafodotin at a dose of 1.0 mg / kg on day 1 of cycle 1 and cycle 5, each cycle being 21 days long.

[0137] Bortezomib was administered at 1.3 mg / m 2 on days 1, 4, 8, and 11 of every 21-day cycle.

[0138] Lenalidomide is administered orally at a dose of 25 mg on days 1-14 of a 21-day cycle for eight induction cycles. 2 In patients with refractory glaucoma, lenalidomide is administered at a dose of 10 mg on days 1-14 of each 21-day cycle. 2 In patients who achieve an improvement in eGFR greater than 100%, for example confirmed over two measurements two weeks apart, the dose of lenalidomide may be increased as appropriate based on the investigator's discretion.

[0139] Dexamethasone is administered orally at 20 mg on days 1, 2, 4, 5, 8, 9, 11, and 12 of a 21-day cycle for eight induction cycles. Dexamethasone is taken at the same time of day and may be taken at home. For patients who are older than 75 years of age, underweight (body mass index (BMI) less than 18.5), have poorly controlled diabetes mellitus, or have a history of intolerance / adverse events (AEs) to steroid therapy, dexamethasone dosing may be administered on the above days at a dose of 10 mg.

[0140] Maintenance treatment (Q4W): Belantamab + mafodotin + Rd; cycle 9 and onward In some embodiments, belantamab mafodotin is administered in combination with Rd as a maintenance treatment after the first 8 induction cycles. Maintenance treatment follows induction treatment and begins at cycle 9. In some embodiments, each cycle of maintenance treatment is 28 days. Bortezomib is not administered as part of the maintenance treatment.

[0141] Belantamab mafodotin in combination with Rd is administered intravenously (IV) on day 1 of every 28-day cycle, every two 28-day cycles, or every three 28-day cycles.

[0142] In some embodiments, the maintenance treatment comprises administering belantamab mafodotin at a dose of 1.9 mg / kg on day 1 of every cycle from cycle 9 onward (e.g., cycle 9, 10, 11, 12, etc.), each cycle being 28 days long. In some embodiments, the maintenance treatment comprises administering belantamab mafodotin at a dose of 1.4 mg / kg on day 1 of every 2nd cycle from cycle 9 onward (e.g., cycle 9, 11, 13, 15, etc.), each cycle being 28 days long. In some embodiments, the maintenance treatment comprises administering belantamab mafodotin at a dose of 1.9 mg / kg on day 1 of every 2nd cycle from cycle 9 onward (e.g., cycle 9, 11, 13, 15, etc.), each cycle being 28 days long. In some embodiments, the maintenance treatment comprises administering belantamab mafodotin at a dose of 1.0 mg / kg on day 1 of each cycle after cycle 9 (e.g., cycle 9, 10, 11, 12, etc.), where each cycle is 28 days long. In some embodiments, the maintenance treatment comprises administering belantamab mafodotin at a dose of 1.4 mg / kg on day 1 of each cycle after cycle 9 (e.g., cycle 9, 10, 11, 12, etc.), where each cycle is 28 days long.

[0143] In some embodiments, the maintenance treatment comprises administering belantamab mafodotin at a dose of 1.0 mg / kg on day 1 of every 3 cycles, each cycle being 28 days long, starting from cycle 9 (e.g., cycles 9, 12, 15, 18, etc.). In some embodiments, the maintenance treatment comprises administering belantamab mafodotin at a dose of 1.4 mg / kg on day 1 of every 3 cycles, each cycle being 28 days long, starting from cycle 9 (e.g., cycles 9, 12, 15, 18, etc.).

[0144] Lenalidomide is administered orally at a dose of 25 mg on days 1 to 21 of each 28-day cycle until disease progression or unacceptable toxicity. 2 In patients with refractory glaucoma, lenalidomide is administered at a dose of 10 mg on days 1-21 of each 28-day cycle. 2 In patients who achieve an improvement in eGFR > 1.0 (confirmed over two measurements two weeks apart), the dose of lenalidomide may be increased as appropriate based on the investigator's discretion.

[0145] From cycle 9 onwards, dexamethasone is administered orally at 40 mg on days 1, 8, 15, and 22 of a 28-day cycle until disease progression or unacceptable toxicity. Dexamethasone is taken at the same time of day and may be taken at home. For patients who are older than 75 years, underweight (BMI < 18.5), have poorly controlled diabetes mellitus, or have a history of intolerance / adverse events (AEs) to steroid therapy, dexamethasone dosing may be administered at a dose of 20 mg on the days listed above.

[0146] Independently, the dose of nirogacestat administered as part of any of the above combination therapies can be, for example, at least about 50 mg, at least 100 mg, at least 150 mg, at least 200 mg, or at least 250 mg administered once or twice daily, in some embodiments, 100 mg of nirogacestat is administered twice daily.

[0147] kit Further provided is a kit of parts comprising the pharmaceutical composition together with instructions for use. Conveniently, the kit of parts may comprise reagents in predetermined amounts together with instructions for use.

[0148] In some embodiments, disclosed herein is a kit comprising the combination therapy disclosed herein. The kit may include multiple syringes, ampoules, foil packets, or blister packs, each containing a unit dose of the kit components described herein. The containers of the kit may be airtight, waterproof (e.g., impervious to changes in moisture and evaporation), and / or light-tight. The kit may include a device suitable for administering the components, such as a syringe, inhaler, pipette, tweezers, measuring spoon, dropper (e.g., eye dropper), swab (e.g., cotton bud or wooden swab), or any such delivery device. In some embodiments, the device may be, for example, a medical implant device packaged for surgical insertion. The kit disclosed herein may include one or more reagents or instruments that allow the above method to be performed.

[0149] In addition to the above components, instructions for use may be provided in the kit. These instructions may be included in the kit in various forms, such as a suitable medium or substrate (e.g., a sheet or sheets of paper with information printed thereon), in the kit packaging, in a package insert, etc. In some embodiments, the instructions may be provided on a computer readable medium (e.g., a jump / thumb drive, CD, etc.) on which the information is recorded, or at a website address that can be used to access the information at the website via the Internet.

[0150] device Another aspect of the present disclosure provides a pre-filled syringe or auto-injection device comprising the combination therapy described herein. In some embodiments, the combination is stored in a container, a pre-filled syringe, a syringe, or an auto-injection device.

[0151] Those skilled in the art will appreciate that there are many variations and modifications to the above-described embodiments that fall within the scope of the appended claims. EXAMPLES

[0152] Example 1 Patients newly diagnosed with multiple myeloma and ineligible for autologous stem cell transplant are administered a combination therapy comprising: (a) a therapeutically effective amount of belantamab mafodotin; (b) a standard of care comprising: (i) a therapeutically effective amount of a proteasome inhibitor; (ii) a therapeutically effective amount of an immunomodulatory imido drug; and (iii) a therapeutically effective amount of a corticosteroid. The combination therapy comprises: (a) belantamab mafodotin at a dose of 1.0 mg / kg on day 1 of cycles 1 and 5, and belantamab mafodotin at a dose of 1.0 mg / kg on day 1 of every third cycle starting with cycle 9; (b) bortezomib at a dose of 1.3 mg / m for eight induction cycles. 2 (c) lenalidomide is administered (1) orally at a dose of 25 mg on days 1 through 14 of a 21-day cycle for eight induction cycles, or (2) at a rate of 30 to 60 mL / min / 1.73 m 2 and (d) for eight induction cycles, orally administering dexamethasone at a dose of 20 mg on days 1, 2, 4, 5, 8, 9, 11, and 12 of a 21-day cycle.

[0153] Patients receiving this combination therapy experience an additive therapeutic benefit compared to patients receiving standard treatment alone.

[0154] Example 2 Patients newly diagnosed with multiple myeloma and ineligible for autologous stem cell transplant are administered a combination therapy comprising: (a) a therapeutically effective amount of belantamab mafodotin; (b) a standard of care comprising: (i) a therapeutically effective amount of a proteasome inhibitor; (ii) a therapeutically effective amount of an immunomodulatory imido drug; and (iii) a therapeutically effective amount of a corticosteroid. The combination therapy comprises: (a) belantamab mafodotin at a dose of 1.4 mg / kg on day 1 of cycle 1 and 1.0 mg / kg on day 1 of every third cycle starting with cycle 4 for eight induction cycles, each induction cycle being 21 days long; (b) bortezomib at a dose of 1.3 mg / m 2 (c) lenalidomide (1) administered orally at a dose of 25 mg on days 1 through 14 of a 21-day cycle for eight induction treatment cycles, or (2) administered to individuals with an eGFR between 30 and 60 mL / min / 1.73 m 2 orally administering at a dose of 10 mg daily on days 1 through 14 of each 21-day cycle for eight induction treatment cycles; and (d) orally administering dexamethasone (i) at a dose of 20 mg daily on days 1, 2, 4, 5, 8, 9, 11, and 12 of each 21-day cycle for eight induction treatment cycles, or (ii) at a dose of 10 mg daily on days 1, 2, 4, 5, 8, 9, 11, and 12 of each 21-day cycle if the subject is older than 75 years of age or has a body mass index (BMI) less than 18.5.

[0155] The combination therapy may further comprise: (a) belantamab mafodotin at a dose of 1.4 mg / kg administered orally on day 1 of every third cycle, beginning with Cycle 9, where each cycle is 28 days long; (b) lenalidomide (1) at a dose of 25 mg administered orally on days 1-21 of a 28-day cycle, beginning with Cycle 9, or (2) if the individual's eGFR is between 30 and 60 mL / min / 1.73 m2 and (c) dexamethasone (i) from cycle 9 onwards, orally administered at a dose of 40 mg on days 1, 8, 15, and 22, or (ii) if the subject is older than 75 years or has a body mass index (BMI) less than 18.5, orally administered at a dose of 20 mg on days 1, 8, 15, and 22 of each 28 day cycle.

[0156] Patients receiving this combination therapy experience an additive therapeutic benefit compared to patients receiving standard treatment alone.

[0157] Example 3 Patients newly diagnosed with multiple myeloma and ineligible for autologous stem cell transplant are administered a combination therapy comprising: (a) a therapeutically effective amount of belantamab mafodotin; (b) a standard of care comprising: (i) a therapeutically effective amount of a proteasome inhibitor; (ii) a therapeutically effective amount of an immunomodulatory imido drug; and (iii) a therapeutically effective amount of a corticosteroid. The combination therapy comprises: (a) belantamab mafodotin at a dose of 1.9 mg / kg on day 1 of cycle 1 and 1.4 mg / kg on day 1 of every third cycle from cycle 4 onwards for eight induction cycles, each induction cycle being 21 days long; (b) bortezomib at a dose of 1.3 mg / m 2 (c) lenalidomide (1) administered orally at a dose of 25 mg on days 1 through 14 of a 21-day cycle for eight induction treatment cycles, or (2) administered to individuals with an eGFR between 30 and 60 mL / min / 1.73 m 2orally administering at a dose of 10 mg daily on days 1 through 14 of each 21-day cycle for eight induction treatment cycles; and (d) orally administering dexamethasone (i) at a dose of 20 mg daily on days 1, 2, 4, 5, 8, 9, 11, and 12 of each 21-day cycle for eight induction treatment cycles, or (ii) at a dose of 10 mg daily on days 1, 2, 4, 5, 8, 9, 11, and 12 of each 21-day cycle if the subject is older than 75 years of age or has a body mass index (BMI) less than 18.5.

[0158] The combination therapy may further comprise: (a) belantamab mafodotin at a dose of 1.4 mg / kg administered orally on day 1 of every third cycle, beginning with Cycle 9, where each cycle is 28 days long; (b) lenalidomide (1) at a dose of 25 mg administered orally on days 1-21 of a 28-day cycle, beginning with Cycle 9, or (2) if the individual's eGFR is between 30 and 60 mL / min / 1.73 m 2 and (c) dexamethasone (i) from cycle 9 onwards, orally administered at a dose of 40 mg on days 1, 8, 15, and 22, or (ii) if the subject is older than 75 years or has a body mass index (BMI) less than 18.5, orally administered at a dose of 20 mg on days 1, 8, 15, and 22 of each 28 day cycle.

[0159] Patients receiving this combination therapy experience an additive therapeutic benefit compared to patients receiving standard treatment alone.

[0160] Example 4 Patients newly diagnosed with multiple myeloma and ineligible for autologous stem cell transplant are administered a combination therapy comprising: (a) a therapeutically effective amount of belantamab mafodotin; (b) a standard of care comprising: (i) a therapeutically effective amount of a proteasome inhibitor; (ii) a therapeutically effective amount of an immunomodulatory imido drug; and (iii) a therapeutically effective amount of a corticosteroid. The combination therapy comprises: (a) belantamab mafodotin at a dose of 1.9 mg / kg on day 1 of cycles 1 and 4 for eight induction cycles, followed by belantamab mafodotin at a dose of 1.4 mg / kg on day 1 of every third cycle, starting with cycle 7, where each induction cycle is 21 days long; (b) bortezomib at a dose of 1.3 mg / m for eight induction cycles. 2 (c) lenalidomide (1) administered orally at a dose of 25 mg on days 1 through 14 of a 21-day cycle for eight induction treatment cycles, or (2) administered to individuals with an eGFR between 30 and 60 mL / min / 1.73 m 2 orally administering at a dose of 10 mg daily on days 1 through 14 of each 21-day cycle for eight induction treatment cycles; and (d) orally administering dexamethasone (i) at a dose of 20 mg daily on days 1, 2, 4, 5, 8, 9, 11, and 12 of each 21-day cycle for eight induction treatment cycles, or (ii) at a dose of 10 mg daily on days 1, 2, 4, 5, 8, 9, 11, and 12 of each 21-day cycle if the subject is older than 75 years of age or has a body mass index (BMI) less than 18.5.

[0161] The combination therapy may further comprise: (a) belantamab mafodotin at a dose of 1.4 mg / kg administered orally on day 1 of every third cycle, beginning with Cycle 9, where each cycle is 28 days long; (b) lenalidomide (1) at a dose of 25 mg administered orally on days 1-21 of a 28-day cycle, beginning with Cycle 9, or (2) if the individual's eGFR is between 30 and 60 mL / min / 1.73 m 2 and (c) dexamethasone (i) from cycle 9 onwards, orally administered at a dose of 40 mg on days 1, 8, 15, and 22, or (ii) if the subject is older than 75 years or has a body mass index (BMI) less than 18.5, orally administered at a dose of 20 mg on days 1, 8, 15, and 22 of each 28 day cycle.

[0162] Patients receiving this combination therapy experience an additive therapeutic benefit compared to patients receiving standard treatment alone.

[0163] Example 5 Patients newly diagnosed with multiple myeloma and ineligible for autologous stem cell transplant are administered a combination therapy comprising: (a) a therapeutically effective amount of belantamab mafodotin; (b) a standard of care comprising: (i) a therapeutically effective amount of a proteasome inhibitor; (ii) a therapeutically effective amount of an immunomodulatory imido drug; and (iii) a therapeutically effective amount of a corticosteroid. The combination therapy comprises: (a) belantamab mafodotin at a dose of 1.4 mg / kg on day 1 of cycles 1 and 3 for eight induction cycles, followed by belantamab mafodotin at a dose of 1.0 mg / kg on day 1 of every third cycle starting with cycle 6, each induction cycle being 21 days long; (b) bortezomib at a dose of 1.3 mg / m for eight induction cycles. 2(c) lenalidomide (1) administered orally at a dose of 25 mg on days 1 through 14 of a 21-day cycle for eight induction treatment cycles, or (2) administered to individuals with an eGFR between 30 and 60 mL / min / 1.73 m 2 orally administering at a dose of 10 mg daily on days 1 through 14 of each 21-day cycle for eight induction treatment cycles; and (d) orally administering dexamethasone (i) at a dose of 20 mg daily on days 1, 2, 4, 5, 8, 9, 11, and 12 of each 21-day cycle for eight induction treatment cycles, or (ii) at a dose of 10 mg daily on days 1, 2, 4, 5, 8, 9, 11, and 12 of each 21-day cycle if the subject is older than 75 years of age or has a body mass index (BMI) less than 18.5.

[0164] The combination therapy may further comprise: (a) belantamab mafodotin at a dose of 1.0 mg / kg administered orally on day 1 of every 3 cycles beginning with Cycle 9, where each cycle is 28 days long; (b) lenalidomide (1) at a dose of 25 mg administered orally on days 1-21 of a 28-day cycle beginning with Cycle 9, or (2) if the individual's eGFR is between 30 and 60 mL / min / 1.73 m 2 and (c) dexamethasone (i) from cycle 9 onwards, orally administered at a dose of 40 mg on days 1, 8, 15, and 22, or (ii) if the subject is older than 75 years or has a body mass index (BMI) less than 18.5, orally administered at a dose of 20 mg on days 1, 8, 15, and 22 of each 28 day cycle.

[0165] Patients receiving this combination therapy experience an additive therapeutic benefit compared to patients receiving standard treatment alone.

[0166] Example 6 Patients newly diagnosed with multiple myeloma and ineligible for autologous stem cell transplant are administered a combination therapy comprising: (a) a therapeutically effective amount of belantamab mafodotin; (b) a standard of care comprising: (i) a therapeutically effective amount of a proteasome inhibitor; (ii) a therapeutically effective amount of an immunomodulatory imido drug; and (iii) a therapeutically effective amount of a corticosteroid. The combination therapy comprises: (a) belantamab mafodotin at a dose of 1.0 mg / kg on days 1 of cycles 1 and 5 for eight induction cycles, each induction cycle being 21 days long; (b) bortezomib at a dose of 1.3 mg / m for eight induction cycles. 2 (c) lenalidomide (1) administered orally at a dose of 25 mg on days 1 through 14 of a 21-day cycle for eight induction treatment cycles, or (2) administered to individuals with an eGFR between 30 and 60 mL / min / 1.73 m 2 orally administering at a dose of 10 mg daily on days 1 through 14 of each 21-day cycle for eight induction treatment cycles; and (d) orally administering dexamethasone (i) at a dose of 20 mg daily on days 1, 2, 4, 5, 8, 9, 11, and 12 of each 21-day cycle for eight induction treatment cycles, or (ii) at a dose of 10 mg daily on days 1, 2, 4, 5, 8, 9, 11, and 12 of each 21-day cycle if the subject is older than 75 years of age or has a body mass index (BMI) less than 18.5.

[0167] The combination therapy may further comprise: (a) belantamab mafodotin at a dose of 1.0 mg / kg administered orally on day 1 of every 3 cycles beginning with Cycle 9, where each cycle is 28 days long; (b) lenalidomide (1) at a dose of 25 mg administered orally on days 1-21 of a 28-day cycle beginning with Cycle 9, or (2) if the individual's eGFR is between 30 and 60 mL / min / 1.73 m 2 and (c) dexamethasone (i) from cycle 9 onwards, orally administered at a dose of 40 mg on days 1, 8, 15, and 22 of each 28 day cycle, or (ii) if the subject is older than 75 years of age or has a body mass index (BMI) less than 18.5, orally administered at a dose of 20 mg on days 1, 8, 15, and 22 of each 28 day cycle.

[0168] Patients receiving this combination therapy experience an additive therapeutic benefit compared to patients receiving standard treatment alone.

Claims

1. (a) a therapeutically effective amount of an anti-BCMA antigen binding protein; (b) a therapeutically effective amount of a proteasome inhibitor; (c) a therapeutically effective amount of an immunomodulatory imide drug; and (d) a therapeutically effective amount of a corticosteroid; The combination therapy comprising:

2. The combination therapy of claim 1 , wherein the proteasome inhibitor is bortezomib.

3. 3. The combination therapy of claim 1 or 2, wherein the immunomodulatory imide drug is lenalidomide.

4. The combination therapy of any one of claims 1 to 3, wherein the corticosteroid is dexamethasone.

5. The combination therapy of any one of claims 1 to 4, wherein the anti-BCMA antigen binding protein is belantamab mafodotin.

6. 2. The combination therapy of claim 1, wherein the anti-BCMA antigen binding protein is belantamab mafodotin, the proteasome inhibitor is bortezomib, the immunomodulatory imide drug is lenalidomide, and the corticosteroid is dexamethasone.

7. (a) administering belantamab mafodotin according to a schedule selected from the group consisting of: (i) belantamab mafodotin at a dose of 1.9 mg / kg administered Q3 / 4W, with 1.9 mg / kg administered on day 1 of every cycle; (ii) belantamab mafodotin at a dose of 1.4 mg / kg administered Q6 / 8W, with 1.4 mg / kg administered on day 1 of every 2 cycles; (iii) belantamab mafodotin at a dose of 1.9 mg / kg administered Q6 / 8W on day 1 of every 2 cycles; (iv) belantamab mafodotin at a dose of 1.0 mg / kg administered Q3 / 4W, with the 1.0 mg / kg administered on day 1 of each cycle; (v) belantamab mafodotin at a dose of 1.4 mg / kg administered Q3 / 4W, where 1.4 mg / kg is administered on day 1 of every cycle; (vi) belantamab mafodotin at a dose of 1.4 mg / kg administered on day 1 of cycle 1 and, from cycle 4 onwards, 1.0 mg / kg administered on day 1 of every third cycle; (vii) belantamab mafodotin at a dose of 1.9 mg / kg administered on day 1 of cycle 1 and, from cycle 4 onwards, belantamab mafodotin at 1.4 mg / kg administered on day 1 of every 3 cycles; (viii) belantamab mafodotin at a dose of 1.9 mg / kg administered on day 1 of cycles 1 and 4, and from cycle 7 onwards, belantamab mafodotin at 1.4 mg / kg administered on day 1 of every third cycle; (ix) belantamab mafodotin at a dose of 1.4 mg / kg administered on day 1 of cycles 1 and 3, and from cycle 6 onwards belantamab mafodotin at a dose of 1.0 mg / kg administered on day 1 of every third cycle; and (x) belantamab mafodotin at a dose of 1.0 mg / kg administered on day 1 of cycles 1 and 5, and, beginning with cycle 9, belantamab mafodotin at a dose of 1.0 mg / kg administered on day 1 of every 3 cycles; (b) 1.3 mg / m for 8 induction cycles ２ administered subcutaneously (SC) on days 1, 4, 8, and 11 of every 21-day cycle; (c) (1) lenalidomide at a dose of 25 mg administered orally on days 1 to 14 of a 21-day cycle for eight induction cycles; or (2) the individual receives a 30-60 mL / min / 1.73 m ２ 10 mg of lenalidomide administered daily on days 1-14 of each 21-day cycle; and (d) dexamethasone at a dose of 20 mg administered orally on days 1, 2, 4, 5, 8, 9, 11, and 12 of a 21-day cycle for eight induction cycles; The combination therapy of claim 6 comprising:

8. (a) a therapeutically effective amount of an anti-BCMA antigen binding protein; (b) a therapeutically effective amount of an immunomodulatory imide drug; and (c) a therapeutically effective amount of a corticosteroid; The combination therapy of any one of claims 1 to 7, further comprising a second combination therapy comprising:

9. 9. The second combination therapy of claim 8, wherein the immunomodulatory imide drug is lenalidomide.

10. 10. The second combination therapy of claim 8 or 9, wherein the corticosteroid is dexamethasone.

11. The second combination therapy of any one of claims 8 to 10, wherein the anti-BCMA antigen binding protein is belantamab mafodotin.

12. 9. The combination therapy of claim 8, wherein the second combination therapy comprises belantamab mafodotin, lenalidomide, and dexamethasone.

13. administering the second combination therapy (a) administering belantamab mafodotin intravenously according to a schedule selected from the group consisting of: (i) administered on day 1 of every 28-day cycle; (ii) administered on day 1 of every two 28-day cycles; and (iii) administered on day 1 of every three 28-day cycles; (b) (i) lenalidomide orally administered at a dose of 25 mg on days 1 to 21 of each 28 day cycle, or (ii) at a dose of 10 mg on days 1 to 21 of each 28 day cycle; and (c) dexamethasone administered orally at a dose of 20 mg or 40 mg on days 1, 8, 15, and 22 of each 28-day cycle; The combination therapy of claim 12 comprising:

14. A method of treating newly diagnosed multiple myeloma comprising administering to an individual in need thereof a combination therapy according to any one of claims 1 to 7.

15. 15. The method of claim 14, wherein the individual is ineligible for autologous stem cell transplant.

16. The method of claim 14 or 15, further comprising a maintenance therapy comprising a second combination according to any one of claims 8 to 13.

17. A combination therapy according to any one of claims 1 to 7 for use in the manufacture of a medicament for the treatment of newly diagnosed multiple myeloma.

18. 20. The combination therapy of claim 17 for use in the manufacture of a medicament for the treatment of newly diagnosed multiple myeloma in an individual ineligible for autologous stem cell transplantation.

19. The combination therapy of any one of claims 1 to 7 for use in treating newly diagnosed multiple myeloma.

20. 20. The combination therapy of claim 19, used to treat newly diagnosed multiple myeloma in patients who are ineligible for autologous stem cell transplantation.

21. 1. A method of treating multiple myeloma in a subject, comprising: (a) a therapeutically effective amount of an anti-BCMA antigen binding protein; (b) a therapeutically effective amount of a proteasome inhibitor; (c) a therapeutically effective amount of an immunomodulatory imide drug, and (d) a therapeutically effective amount of a corticosteroid; to said subject; the anti-BCMA antigen binding protein is belantamab mafodotin, and the belantamab mafodotin is administered intravenously to the subject according to a schedule selected from the group consisting of: (i) belantamab mafodotin at a dose of 1.9 mg / kg administered on day 1 of every cycle for 8 induction cycles, where each induction cycle is 21 days long; (ii) belantamab mafodotin at a dose of 1.4 mg / kg administered on day 1 of every 2 cycles for 8 induction cycles, where each induction cycle is 21 days long; (iii) belantamab mafodotin at a dose of 1.9 mg / kg administered on day 1 of every 2 cycles for 8 induction cycles, where each induction cycle is 21 days long; (iv) belantamab mafodotin at a dose of 1.0 mg / kg administered on day 1 of every cycle for 8 induction cycles, where each induction cycle is 21 days long; (v) belantamab mafodotin at a dose of 1.4 mg / kg administered on day 1 of every cycle for 8 induction cycles, wherein each induction cycle is 21 days long; (vi) for 8 induction treatment cycles, belantamab mafodotin at a dose of 1.4 mg / kg is administered on day 1 of cycle 1, and, beginning with cycle 4, belantamab mafodotin at a dose of 1.0 mg / kg is administered on day 1 of every 3 cycles, where each induction treatment cycle is 21 days long; (vii) for 8 induction treatment cycles, belantamab mafodotin at a dose of 1.9 mg / kg is administered on day 1 of cycle 1, and, beginning with cycle 4, belantamab mafodotin at a dose of 1.4 mg / kg is administered on day 1 of every 3 cycles, where each induction treatment cycle is 21 days long; (viii) for 8 induction treatment cycles, belantamab mafodotin at a dose of 1.9 mg / kg is administered on day 1 of cycles 1 and 4, and, beginning with cycle 7, belantamab mafodotin at a dose of 1.4 mg / kg is administered on day 1 of every 3 cycles, wherein each induction treatment cycle is 21 days long; (ix) for 8 induction treatment cycles, belantamab mafodotin at a dose of 1.4 mg / kg is administered on day 1 of cycles 1 and 3, and, beginning with cycle 6, belantamab mafodotin at a dose of 1.0 mg / kg is administered on day 1 of every 3 cycles, wherein each induction treatment cycle is 21 days long; (x) belantamab mafodotin at a dose of 1.0 mg / kg is administered on day 1 of cycle 1 and cycle 5 for 8 induction cycles, where each induction cycle is 21 days long; The proteasome inhibitor is bortezomib, and the bortezomib is administered at 1.3 mg / m for eight induction treatment cycles. ２ on days 1, 4, 8, and 11 of every 21 day cycle; the immunomodulatory imide drug is lenalidomide, and the lenalidomide is (i) orally administered to the subject at a dose of 25 mg on each of days 1-14 of each 21-day cycle for eight induction treatment cycles, or (ii) administered to the subject at a blood glucose level of 30-60 mL / min / 1.73 m ２ orally administer to said subject a dose of 10 mg on each of days 1-14 of each 21-day cycle, for eight induction treatment cycles if the subject has an eGFR of the corticosteroid is dexamethasone, and the dexamethasone is (i) orally administered to the subject at a dose of 20 mg on each of days 1, 2, 4, 5, 8, 9, 11, and 12 of each 21-day cycle for eight induction treatment cycles, or (ii) orally administered to the subject at a dose of 10 mg on each of days 1, 2, 4, 5, 8, 9, 11, and 12 of each 21-day cycle for eight induction treatment cycles if the subject is older than 75 years of age or has a body mass index (BMI) less than 18.5; method.

22. After the eight induction treatment cycles, (a) a therapeutically effective amount of an anti-BCMA antigen binding protein; (b) a therapeutically effective amount of an immunomodulatory imide drug; and (c) a therapeutically effective amount of a corticosteroid; and further comprising administering to said subject a maintenance therapy comprising The anti-BCMA antigen binding protein is belantamab mafodotin, and the belantamab mafodotin is administered intravenously according to a schedule selected from the group consisting of: (i) administered on day 1 of every 28-day cycle; (ii) administered on day 1 of every two 28-day cycles; and (iii) administered on day 1 of every three 28-day cycles; the immunomodulatory imide drug is lenalidomide, and the lenalidomide is administered (i) at a dose of 25 mg on each of days 1-21 of each 28 day cycle, or (ii) at a dose of 30-60 mL / min / 1.73 m ２ orally administered to said subject at a dose of 10 mg on days 1-21 of each 28 day cycle if the subject has an eGFR of the corticosteroid is dexamethasone, which is orally administered to the subject (i) at a dose of 40 mg on days 1, 8, 15, and 22 of each 28 day cycle, or (ii) at a dose of 20 mg on days 1, 8, 15, and 22 of each 28 day cycle if the subject is older than 75 years old or has a body mass index (BMI) less than 18.5; 22. The method of claim 21.

23. To the subject, administering belantamab mafodotin, wherein the belantamab mafodotin is administered intravenously to the subject at a dose of 1.9 mg / kg on day 1 of each cycle for eight induction treatment cycles, wherein each induction treatment cycle is 21 days long; administering bortezomib at a dose of 1.3 mg / m for eight induction treatment cycles. ２ on days 1, 4, 8, and 11 of every 21 day cycle; administering lenalidomide to the subject, wherein the lenalidomide is (i) orally administered to the subject at a dose of 25 mg on each of days 1-14 of each 21-day cycle for eight induction treatment cycles, or (ii) the subject's eGFR is between 30-60 mL / min / 1.73 m ２ is orally administered to the subject at a dose of 10 mg on each of days 1-14 of each 21-day cycle for eight induction treatment cycles; and administering dexamethasone, wherein the dexamethasone is (i) orally administered to the subject at a dose of 20 mg on days 1, 2, 4, 5, 8, 9, 11, and 12 of each 21-day cycle for eight induction treatment cycles, or (ii) orally administered to the subject at a dose of 10 mg on days 1, 2, 4, 5, 8, 9, 11, and 12 of each 21-day cycle for eight induction treatment cycles if the subject is older than 75 years old or has a body mass index (BMI) less than 18.5; and After the eight induction treatment cycles, belantamab mafodotin, wherein said belantamab mafodotin is administered intravenously to said subject on day 1 of each cycle at a dose of 1.9 mg / kg starting with cycle 9, each cycle being 28 days long; (i) lenalidomide at a dose of 25 mg on each of days 1-21 of each 28 day cycle, or (ii) when the subject's eGFR is between 30-60 mL / min / 1.73 m ２ is orally administered to said subject at a dose of 10 mg on days 1 to 21 of each 28 day cycle; comprising dexamethasone, which is orally administered to the subject (i) at a dose of 40 mg on days 1, 8, 15, and 22 of each 28 day cycle, or (ii) at a dose of 20 mg on days 1, 8, 15, and 22 of each 28 day cycle if the subject is older than 75 years or has a body mass index (BMI) less than 18.5; administering maintenance therapy to said subject; 23. The method of claim 21 or 22, comprising:

24. To the subject, administering belantamab mafodotin, wherein the belantamab mafodotin is administered intravenously to the subject at a dose of 1.4 mg / kg on day 1 of every 2 cycles for 8 induction treatment cycles, wherein each induction treatment cycle is 21 days long; administering bortezomib at a dose of 1.3 mg / m for eight induction treatment cycles. ２ on days 1, 4, 8, and 11 of every 21 day cycle; administering lenalidomide to the subject, wherein the lenalidomide is (i) orally administered to the subject at a dose of 25 mg on each of days 1-14 of each 21-day cycle for eight induction treatment cycles, or (ii) the subject's eGFR is between 30-60 mL / min / 1.73 m ２ is orally administered to the subject at a dose of 10 mg on each of days 1-14 of each 21-day cycle for eight induction treatment cycles; and administering dexamethasone, wherein the dexamethasone is (i) orally administered to the subject at a dose of 20 mg on days 1, 2, 4, 5, 8, 9, 11, and 12 of each 21-day cycle for eight induction treatment cycles, or (ii) orally administered to the subject at a dose of 10 mg on days 1, 2, 4, 5, 8, 9, 11, and 12 of each 21-day cycle for eight induction treatment cycles if the subject is older than 75 years old or has a body mass index (BMI) less than 18.5; and After the eight induction treatment cycles, belantamab mafodotin, wherein said belantamab mafodotin is administered intravenously to said subject at a dose of 1.4 mg / kg on day 1 of every 2 cycles starting with cycle 9, each cycle being 28 days long; (i) lenalidomide at a dose of 25 mg on each of days 1-21 of each 28 day cycle, or (ii) when the subject's eGFR is between 30-60 mL / min / 1.73 m ２ is orally administered to said subject at a dose of 10 mg on days 1 to 21 of each 28 day cycle; comprising dexamethasone, which is orally administered to the subject (i) at a dose of 40 mg on days 1, 8, 15, and 22 of each 28 day cycle, or (ii) at a dose of 20 mg on days 1, 8, 15, and 22 of each 28 day cycle if the subject is older than 75 years or has a body mass index (BMI) less than 18.5; administering maintenance therapy to said subject; 23. The method of claim 21 or 22, comprising:

25. To the subject, administering belantamab mafodotin, wherein the belantamab mafodotin is administered intravenously to the subject at a dose of 1.9 mg / kg on day 1 of every 2 cycles for 8 induction treatment cycles, wherein each induction treatment cycle is 21 days long; administering bortezomib at a dose of 1.3 mg / m for eight induction treatment cycles. ２ on days 1, 4, 8, and 11 of every 21 day cycle; administering lenalidomide to the subject, wherein the lenalidomide is (i) orally administered to the subject at a dose of 25 mg on each of days 1-14 of each 21-day cycle for eight induction treatment cycles, or (ii) the subject's eGFR is between 30-60 mL / min / 1.73 m ２ is orally administered to the subject at a dose of 10 mg on each of days 1-14 of each 21-day cycle for eight induction treatment cycles; and administering dexamethasone, wherein the dexamethasone is (i) orally administered to the subject at a dose of 20 mg on days 1, 2, 4, 5, 8, 9, 11, and 12 of each 21-day cycle for eight induction treatment cycles, or (ii) orally administered to the subject at a dose of 10 mg on days 1, 2, 4, 5, 8, 9, 11, and 12 of each 21-day cycle for eight induction treatment cycles if the subject is older than 75 years old or has a body mass index (BMI) less than 18.5; and After the eight induction treatment cycles, belantamab mafodotin, wherein said belantamab mafodotin is administered intravenously to said subject at a dose of 1.9 mg / kg on day 1 of every 2 cycles starting with cycle 9, each cycle being 28 days long; (i) lenalidomide at a dose of 25 mg on each of days 1-21 of each 28 day cycle, or (ii) when the subject's eGFR is between 30-60 mL / min / 1.73 m ２ is orally administered to said subject at a dose of 10 mg on days 1 to 21 of each 28 day cycle; comprising dexamethasone, which is orally administered to the subject (i) at a dose of 40 mg on days 1, 8, 15, and 22 of each 28 day cycle, or (ii) at a dose of 20 mg on days 1, 8, 15, and 22 of each 28 day cycle if the subject is older than 75 years or has a body mass index (BMI) less than 18.5; administering maintenance therapy to said subject; 23. The method of claim 21 or 22, comprising:

26. To the subject, administering belantamab mafodotin, wherein the belantamab mafodotin is administered intravenously to the subject at a dose of 1.0 mg / kg on day 1 of each cycle for eight induction treatment cycles, wherein each induction treatment cycle is 21 days long; administering bortezomib at a dose of 1.3 mg / m for eight induction treatment cycles. ２ on days 1, 4, 8, and 11 of every 21 day cycle; administering lenalidomide to the subject, wherein the lenalidomide is (i) orally administered to the subject at a dose of 25 mg on each of days 1-14 of each 21-day cycle for eight induction treatment cycles, or (ii) the subject's eGFR is between 30-60 mL / min / 1.73 m ２ is orally administered to the subject at a dose of 10 mg on each of days 1-14 of each 21-day cycle for eight induction treatment cycles; and administering dexamethasone, wherein the dexamethasone is (i) orally administered to the subject at a dose of 20 mg on days 1, 2, 4, 5, 8, 9, 11, and 12 of each 21-day cycle for eight induction treatment cycles, or (ii) orally administered to the subject at a dose of 10 mg on days 1, 2, 4, 5, 8, 9, 11, and 12 of each 21-day cycle for eight induction treatment cycles if the subject is older than 75 years old or has a body mass index (BMI) less than 18.5; and After the eight induction treatment cycles, belantamab mafodotin, wherein said belantamab mafodotin is administered intravenously to said subject on day 1 of each cycle at a dose of 1.0 mg / kg starting with cycle 9, each cycle being 28 days long; (i) lenalidomide at a dose of 25 mg on each of days 1-21 of each 28 day cycle, or (ii) when the subject's eGFR is between 30-60 mL / min / 1.73 m ２ is orally administered to said subject at a dose of 10 mg on days 1 to 21 of each 28 day cycle; comprising dexamethasone, which is orally administered to the subject (i) at a dose of 40 mg on days 1, 8, 15, and 22 of each 28 day cycle, or (ii) at a dose of 20 mg on days 1, 8, 15, and 22 of each 28 day cycle if the subject is older than 75 years or has a body mass index (BMI) less than 18.5; administering maintenance therapy to said subject; 23. The method of claim 21 or 22, comprising:

27. To the subject, administering belantamab mafodotin, wherein the belantamab mafodotin is administered intravenously to the subject at a dose of 1.4 mg / kg on day 1 of each cycle for eight induction treatment cycles, wherein each induction treatment cycle is 21 days long; administering bortezomib at a dose of 1.3 mg / m for eight induction treatment cycles. ２ on days 1, 4, 8, and 11 of every 21 day cycle; administering lenalidomide to the subject, wherein the lenalidomide is (i) orally administered to the subject at a dose of 25 mg on each of days 1-14 of each 21-day cycle for eight induction treatment cycles, or (ii) the subject's eGFR is between 30-60 mL / min / 1.73 m ２ is orally administered to the subject at a dose of 10 mg on each of days 1-14 of each 21-day cycle for eight induction treatment cycles; and administering dexamethasone, wherein the dexamethasone is (i) orally administered to the subject at a dose of 20 mg on days 1, 2, 4, 5, 8, 9, 11, and 12 of each 21-day cycle for eight induction treatment cycles, or (ii) orally administered to the subject at a dose of 10 mg on days 1, 2, 4, 5, 8, 9, 11, and 12 of each 21-day cycle for eight induction treatment cycles if the subject is older than 75 years old or has a body mass index (BMI) less than 18.5; and After the eight induction treatment cycles, belantamab mafodotin, wherein said belantamab mafodotin is administered intravenously to said subject on day 1 of each cycle at a dose of 1.4 mg / kg starting with cycle 9, each cycle being 28 days long; (i) lenalidomide at a dose of 25 mg on each of days 1-21 of each 28 day cycle, or (ii) when the subject's eGFR is between 30-60 mL / min / 1.73 m ２ is orally administered to said subject at a dose of 10 mg on days 1 to 21 of each 28 day cycle; comprising dexamethasone, which is orally administered to the subject (i) at a dose of 40 mg on days 1, 8, 15, and 22 of each 28 day cycle, or (ii) at a dose of 20 mg on days 1, 8, 15, and 22 of each 28 day cycle if the subject is older than 75 years or has a body mass index (BMI) less than 18.5; administering maintenance therapy to said subject; 23. The method of claim 21 or 22, comprising:

28. To the subject, administering belantamab mafodotin, wherein the belantamab mafodotin is administered intravenously to the subject at a dose of 1.4 mg / kg on day 1 of cycle 1 for eight induction cycles, and from cycle 4 on, at a dose of 1.0 mg / kg on day 1 of every third cycle, wherein each induction cycle is 21 days long; administering bortezomib at a dose of 1.3 mg / m for eight induction treatment cycles. ２ on days 1, 4, 8, and 11 of every 21 day cycle; administering lenalidomide to the subject, wherein the lenalidomide is (i) orally administered to the subject at a dose of 25 mg on each of days 1-14 of each 21-day cycle for eight induction treatment cycles, or (ii) the subject's eGFR is between 30-60 mL / min / 1.73 m ２ is orally administered to the subject at a dose of 10 mg on each of days 1-14 of each 21-day cycle for eight induction treatment cycles; and administering dexamethasone, wherein the dexamethasone is (i) orally administered to the subject at a dose of 20 mg on days 1, 2, 4, 5, 8, 9, 11, and 12 of each 21-day cycle for eight induction treatment cycles, or (ii) orally administered to the subject at a dose of 10 mg on days 1, 2, 4, 5, 8, 9, 11, and 12 of each 21-day cycle for eight induction treatment cycles if the subject is older than 75 years old or has a body mass index (BMI) less than 18.5; and After the eight induction treatment cycles, belantamab mafodotin, wherein said belantamab mafodotin is administered intravenously to said subject at a dose of 1.0 mg / kg on day 1 of every 3 cycles starting with cycle 9, each cycle being 28 days long; (i) lenalidomide at a dose of 25 mg on each of days 1-21 of each 28 day cycle, or (ii) when the subject's eGFR is between 30-60 mL / min / 1.73 m ２ is orally administered to said subject at a dose of 10 mg on days 1 to 21 of each 28 day cycle; comprising dexamethasone, which is orally administered to the subject (i) at a dose of 40 mg on days 1, 8, 15, and 22 of each 28 day cycle, or (ii) at a dose of 20 mg on days 1, 8, 15, and 22 of each 28 day cycle if the subject is older than 75 years or has a body mass index (BMI) less than 18.5; administering maintenance therapy to said subject; 23. The method of claim 21 or claim 22, comprising:

29. To the subject, administering belantamab mafodotin, wherein the belantamab mafodotin is administered intravenously to the subject at a dose of 1.9 mg / kg on day 1 of cycle 1 for eight induction cycles, and from cycle 4 on, at a dose of 1.4 mg / kg on day 1 of every third cycle, wherein each induction cycle is 21 days long; administering bortezomib at a dose of 1.3 mg / m for eight induction treatment cycles. ２ on days 1, 4, 8, and 11 of every 21 day cycle; administering lenalidomide to the subject, wherein the lenalidomide is (i) orally administered to the subject at a dose of 25 mg on each of days 1-14 of each 21-day cycle for eight induction treatment cycles, or (ii) the subject's eGFR is between 30-60 mL / min / 1.73 m ２ is orally administered to the subject at a dose of 10 mg on each of days 1-14 of each 21-day cycle for eight induction treatment cycles; and administering dexamethasone, wherein the dexamethasone is (i) orally administered to the subject at a dose of 20 mg on days 1, 2, 4, 5, 8, 9, 11, and 12 of each 21-day cycle for eight induction treatment cycles, or (ii) orally administered to the subject at a dose of 10 mg on days 1, 2, 4, 5, 8, 9, 11, and 12 of each 21-day cycle for eight induction treatment cycles if the subject is older than 75 years old or has a body mass index (BMI) less than 18.5; and After the eight induction treatment cycles, belantamab mafodotin, wherein said belantamab mafodotin is administered intravenously to said subject at a dose of 1.4 mg / kg on day 1 of every 3 cycles starting with cycle 9, each cycle being 28 days long; (i) lenalidomide at a dose of 25 mg on each of days 1-21 of each 28 day cycle, or (ii) when the subject's eGFR is between 30-60 mL / min / 1.73 m ２ is orally administered to said subject at a dose of 10 mg on days 1 to 21 of each 28 day cycle; comprising dexamethasone, which is orally administered to the subject (i) at a dose of 40 mg on days 1, 8, 15, and 22 of each 28 day cycle, or (ii) at a dose of 20 mg on days 1, 8, 15, and 22 of each 28 day cycle if the subject is older than 75 years or has a body mass index (BMI) less than 18.5; administering maintenance therapy to said subject; 23. The method of claim 21 or 22, comprising:

30. To the subject, administering belantamab mafodotin to the subject intravenously at a dose of 1.9 mg / kg on day 1 of cycles 1 and 4 for eight induction cycles, and from cycle 7 on, at a dose of 1.4 mg / kg on day 1 of every third cycle, wherein each induction cycle is 21 days long; administering bortezomib at a dose of 1.3 mg / m for eight induction treatment cycles. ２ on days 1, 4, 8, and 11 of every 21 day cycle; administering lenalidomide to the subject, wherein the lenalidomide is (i) orally administered to the subject at a dose of 25 mg on each of days 1-14 of each 21-day cycle for eight induction treatment cycles, or (ii) the subject's eGFR is between 30-60 mL / min / 1.73 m ２ is orally administered to the subject at a dose of 10 mg on each of days 1-14 of each 21-day cycle for eight induction treatment cycles; and administering dexamethasone, wherein the dexamethasone is (i) orally administered to the subject at a dose of 20 mg on days 1, 2, 4, 5, 8, 9, 11, and 12 of each 21-day cycle for eight induction treatment cycles, or (ii) orally administered to the subject at a dose of 10 mg on days 1, 2, 4, 5, 8, 9, 11, and 12 of each 21-day cycle for eight induction treatment cycles if the subject is older than 75 years old or has a body mass index (BMI) less than 18.5; and After the eight induction treatment cycles, belantamab mafodotin, wherein said belantamab mafodotin is administered intravenously to said subject at a dose of 1.4 mg / kg on day 1 of every 3 cycles starting with cycle 9, each cycle being 28 days long; (i) lenalidomide at a dose of 25 mg on each of days 1-21 of each 28 day cycle, or (ii) when the subject's eGFR is between 30-60 mL / min / 1.73 m ２ is orally administered to said subject at a dose of 10 mg on days 1 to 21 of each 28 day cycle; comprising dexamethasone, which is orally administered to the subject (i) at a dose of 40 mg on days 1, 8, 15, and 22 of each 28 day cycle, or (ii) at a dose of 20 mg on days 1, 8, 15, and 22 of each 28 day cycle if the subject is older than 75 years or has a body mass index (BMI) less than 18.5; administering maintenance therapy to said subject; 23. The method of claim 21 or 22, comprising:

31. To the subject, administering belantamab mafodotin, wherein the belantamab mafodotin is administered intravenously to the subject at a dose of 1.4 mg / kg on day 1 of cycles 1 and 3 for eight induction cycles, and from cycle 6 on, at a dose of 1.0 mg / kg on day 1 of every third cycle, wherein each induction cycle is 21 days long; administering bortezomib at a dose of 1.3 mg / m for eight induction treatment cycles. ２ on days 1, 4, 8, and 11 of every 21 day cycle; administering lenalidomide to the subject, wherein the lenalidomide is (i) orally administered to the subject at a dose of 25 mg on each of days 1-14 of each 21-day cycle for eight induction treatment cycles, or (ii) the subject's eGFR is between 30-60 mL / min / 1.73 m ２ is orally administered to the subject at a dose of 10 mg on each of days 1-14 of each 21-day cycle for eight induction treatment cycles; and administering dexamethasone, wherein the dexamethasone is (i) orally administered to the subject at a dose of 20 mg on days 1, 2, 4, 5, 8, 9, 11, and 12 of each 21-day cycle for eight induction treatment cycles, or (ii) orally administered to the subject at a dose of 10 mg on days 1, 2, 4, 5, 8, 9, 11, and 12 of each 21-day cycle for eight induction treatment cycles if the subject is older than 75 years old or has a body mass index (BMI) less than 18.5; and After the eight induction treatment cycles, belantamab mafodotin, wherein said belantamab mafodotin is administered intravenously to said subject at a dose of 1.0 mg / kg on day 1 of every 3 cycles starting with cycle 9, each cycle being 28 days long; (i) lenalidomide at a dose of 25 mg on each of days 1-21 of each 28 day cycle, or (ii) when the subject's eGFR is between 30-60 mL / min / 1.73 m ２ is orally administered to said subject at a dose of 10 mg on days 1 to 21 of each 28 day cycle; comprising dexamethasone, which is orally administered to the subject (i) at a dose of 40 mg on days 1, 8, 15, and 22 of each 28 day cycle, or (ii) at a dose of 20 mg on days 1, 8, 15, and 22 of each 28 day cycle if the subject is older than 75 years or has a body mass index (BMI) less than 18.5; administering maintenance therapy to said subject; 23. The method of claim 21 or 22, comprising:

32. To the subject, administering belantamab mafodotin, wherein the belantamab mafodotin is administered intravenously to the subject at a dose of 1.0 mg / kg on days 1 of cycle 1 and cycle 5 for eight induction cycles, wherein each induction cycle is 21 days long; administering bortezomib at a dose of 1.3 mg / m for eight induction treatment cycles. ２ on days 1, 4, 8, and 11 of every 21 day cycle; administering lenalidomide to the subject, wherein the lenalidomide is (i) orally administered to the subject at a dose of 25 mg on each of days 1-14 of each 21-day cycle for eight induction treatment cycles, or (ii) the subject's eGFR is between 30-60 mL / min / 1.73 m ２ is orally administered to the subject at a dose of 10 mg on each of days 1-14 of each 21-day cycle for eight induction treatment cycles; and administering dexamethasone, wherein the dexamethasone is (i) orally administered to the subject at a dose of 20 mg on days 1, 2, 4, 5, 8, 9, 11, and 12 of each 21-day cycle for eight induction treatment cycles, or (ii) orally administered to the subject at a dose of 10 mg on days 1, 2, 4, 5, 8, 9, 11, and 12 of each 21-day cycle for eight induction treatment cycles if the subject is older than 75 years old or has a body mass index (BMI) less than 18.5; and After the eight induction treatment cycles, belantamab mafodotin, wherein said belantamab mafodotin is administered intravenously to said subject at a dose of 1.0 mg / kg on day 1 of every 3 cycles starting with cycle 9, each cycle being 28 days long; (i) lenalidomide at a dose of 25 mg on each of days 1-21 of each 28 day cycle, or (ii) when the subject's eGFR is between 30-60 mL / min / 1.73 m ２ is orally administered to said subject at a dose of 10 mg on days 1 to 21 of each 28 day cycle; comprising dexamethasone, which is orally administered to the subject (i) at a dose of 40 mg on days 1, 8, 15, and 22 of each 28 day cycle, or (ii) at a dose of 20 mg on days 1, 8, 15, and 22 of each 28 day cycle if the subject is older than 75 years or has a body mass index (BMI) less than 18.5; administering maintenance therapy to said subject; 23. The method of claim 21 or 22, comprising:

33. The method of any one of claims 21 to 32, wherein the multiple myeloma is newly diagnosed multiple myeloma.

34. 34. The method of claim 33, wherein the subject is ineligible for autologous stem cell transplant.

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