Methods for Treating AL Amyloidosis

Abstract

Antibody formulations and methods useful for treating patients with AL amyloidosis. The present disclosure relates to a method for treating certain AL amyloidosis patients. Provided herein is a method for treating patients with AL amyloidosis, comprising administering to the patient an effective dose of an antibody that competes with 2A4 (ATCC Accession No. PTA-9662) or 7D8 (ATCC Accession No. PTA-9468) for binding to human amyloid A peptide or human kappa or lambda light chain immunoglobulin, or competes with 11-1F4 (ATCC Accession No. PTA-105) for binding to kappa light chain immunoglobulin; and administering to the patient a therapeutically effective dose of daratumumab 5 to 90 minutes after completing the step of administering the antibody, wherein the patient (a) has Mayo stage IV AL amyloidosis.

Description

[Technical field]

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS This application claims priority to U.S. Provisional Patent Application No. 63 / 298,396, filed January 11, 2022, the contents of which are incorporated herein by reference in their entirety.

[0002] Sequence Listing This application contains a Sequence Listing that has been submitted electronically as an XML file entitled "50887-0021WO1_SL_ST26.XML." The XML file was created on Dec. 30, 2022 and is 22,879 bytes in size. The material in the XML file is hereby incorporated by reference in its entirety.

[0003] Field The present disclosure relates to the technical fields of immunology and medicine. [Background technology]

[0004] background AL amyloidosis involves a hematological disorder caused by clonal plasma cells that produce immunoglobulin light chains that may be misfolded and contribute to the disease. Overproduction of misfolded light chains by plasma cells results in the deposition of abnormal AL protein (amyloid) in tissues and organs of individuals with AL amyloidosis. Clinical features of AL amyloidosis include a variety of symptoms and organ dysfunction, including cardiac, renal and hepatic dysfunction, gastrointestinal complications, neuropathy and macroglossia. The mechanism by which amyloidogenic immunoglobulin light chains cause organ dysfunction has not been fully characterized, but it has been hypothesized that both amyloid deposition and prefibrillar aggregation may contribute to the cytotoxic effects on organs observed in patients with AL amyloidosis. Although AL amyloidosis may occur concomitantly in a subset of patients with multiple myeloma (up to 15%) or monoclonal gammopathy of undetermined significance (MGUS; up to 9%), AL amyloidosis is a disease entity in its own right.

[0005] AL amyloidosis is a rare disorder with an estimated incidence of 8 cases per 1,000,000. Approximately 1200 to 3200 new cases of AL amyloidosis are reported annually in the United States. Two-thirds of patients with AL amyloidosis are male, and less than 5% of patients are under 40 years of age. Both the cause and origin of AL amyloidosis remain poorly understood. Disease outcomes for patients with AL amyloidosis can be predicted based on the Mayo 4-stage prognostic staging system discussed in Kumar et al., 2012 (Kumar et al., Revised Prognostic Staging System for Light Chain Amyloidosis Incorporating Cardiac Biomarkers and Serum Free Light Chain Measurements, J Clin Oncol 30:989-995 2012), where outcomes for stage IV patients are very severe.

[0006] Current treatments for patients with AL amyloidosis aim to reduce or eliminate bone marrow damage, i.e., plasma cells responsible for producing light chains, thereby limiting or stopping the production of amyloid. The most aggressive treatment options include stem cell transplantation and high-dose chemotherapy for patients who can tolerate it. Other therapeutic regimens include drug combinations such as melphalan, prednisone, and dexamethasone, often used to treat hematological malignancies, and proteosome inhibitors such as bortezomib to reduce light chain production. There are currently no approved treatments for AL amyloidosis that directly target the potentially toxic forms of amyloidogenic proteins. Some treatment options can provide some relief from morbidity associated with AL amyloidosis, but few, if any, have been demonstrated to improve patient outcomes.

[0007] In 2021, the FDA approved the use of subcutaneous daratumumab in combination with cyclophosphamide-bortezomib-dexamethasone (CyBorD) for the treatment of patients with newly diagnosed AL amyloidosis with Mayo stages I to IIIA (https: / / www.fda.gov / drugs / drug-approvals-and-databases / fda-grants-accelerated-approval-darzalex-faspro-newly-diagnosed-light-chain-amyloidosis). Despite this, no clear survival benefit has been observed for patients with AL amyloidosis treated with daratumumab. In the phase 3 ANDROMEDA study, 56 patients died (27 in the daratumumab group (daratumumab + CyBorD) and 29 in the control group (CyBorD)) during a median follow-up period of 11.4 months. Kastritis et al. N Engl J Med. 2021 Jul 1;385(1):46-58.

[0008] Furthermore, Mayo stage IV patients with AL amyloidosis represent a patient subset with no currently approved treatment and a very high burden of morbidity and mortality, a population estimated to amount to approximately 2,760 patients in the United States and 6,900 to 10,350 patients in the United States and European Union combined. Thus, there is an unmet need for therapies that improve health, including reducing the risk of mortality or enhancing quality of life, in patients with AL amyloidosis. [Prior art documents] [Non-patent literature]

[0009] [Non-Patent Document 1] Kumar et al., Revised Prognostic Staging System for Light Chain Amyloidosis Incorporating Cardiac Biomarkers and Serum Free Light Chain Measurements, J Clin Oncol 30:989-995 2012 Summary of the Invention [Means for solving the problem]

[0010] overview The present disclosure relates to methods of treating certain patients with AL amyloidosis.

[0011] Provided herein is a method of treating a patient having AL amyloidosis, the method comprising administering to the patient an effective dosage of an antibody that competes with 2A4 (ATCC Accession No. PTA-9662) or 7D8 (ATCC Accession No. PTA-9468) for binding to human amyloid A peptide or human kappa or lambda light chain immunoglobulin, or that competes with 11-1F4 (ATCC Accession No. PTA-105) for binding to kappa light chain immunoglobulin; and administering to the patient a therapeutically effective dosage of daratumumab 5 to 90 minutes after completion of the step of administering the antibody, wherein the patient (a) has Mayo stage IV AL amyloidosis.

[0012] In some embodiments, the patient has a 6MWT > 150 meters and an EF > 50%. In some embodiments, the patient has a 6MWT > 30 meters and ≦ 550 meters. In some embodiments, the patient has an EF > 50%. In some embodiments, the patient has a 6MWT > 150 meters. In some embodiments, the selected patient has a cardiac complication. In some embodiments, the selected patient has Mayo stage IV AL amyloidosis and has a cardiac complication. In some embodiments, the selected patient has Mayo stage IV AL amyloidosis, a cardiac complication, and a 6MWT > 30 meters and ≦ 550 meters. In some embodiments, the therapeutically effective dose of daratumumab to the patient is administered approximately 60 minutes after completion of administration of the antibody.

[0013] Also provided herein is a method of treating a patient with AL amyloidosis, comprising: (a) Below: (i) The patient's Mayo stage of AL amyloidosis; (ii) the patient's 6-minute walk distance (6MWT); (iii) the patient's ejection fraction (EF); or (iv) Cardiac complications of the patient determining one or more of: (b) if the patient has Mayo stage IV amyloidosis, selecting the patient for treatment with (i) an antibody that competes with 2A4 (ATCC Accession No. PTA-9662) or 7D8 (ATCC Accession No. PTA-9468) for binding to human amyloid A peptide or human kappa or lambda light chain immunoglobulin, or competes with 11-1F4 (ATCC Accession No. PTA-105) for binding to kappa light chain immunoglobulin, and (ii) daratumumab; (c) administering to the selected patient an effective dose of the antibody; and (d) administering a therapeutically effective dose of daratumumab to the selected patient 5 to 90 minutes after completion of the antibody administering step. A method is provided, comprising:

[0014] In some embodiments, the selected patient has a 6MWT > 150 meters and an EF > 50%. In some embodiments, the selected patient has a 6MWT > 30 meters and < 550 meters. In some embodiments, the selected patient has an EF > 50%. In some embodiments, the selected patient has a 6MWT > 150 meters. In some embodiments, the selected patient has a 6MWT > 30 meters and < 550 meters. In some embodiments, the selected patient has a cardiac complication. In some embodiments, the selected patient has Mayo stage IV AL amyloidosis and has a cardiac complication. In some embodiments, the selected patient has Mayo stage IV AL amyloidosis, a cardiac complication, and a 6MWT > 30 meters and < 550 meters.

[0015] In some embodiments, the therapeutically effective dose of daratumumab is administered to the patient approximately 60 minutes after completion of administration of the antibody.

[0016] Provided herein is a method of treating a patient with Mayo stage IV AL amyloidosis and having NYHA class III or NYHA class IV, comprising the steps of administering to the patient a therapeutically effective dose of an antibody that competes with 2A4 (ATCC Accession No. PTA-9662) or 7D8 (ATCC Accession No. PTA-9468) for binding to human amyloid A peptide or human kappa or lambda light chain immunoglobulin, or competes with an amount of 11-1F4 (ATCC Accession No. PTA-105) for binding to kappa light chain immunoglobulin; and administering a therapeutically effective dose of daratumumab to the patient 5 to 90 minutes after completion of the tap, wherein the patient has one or more of the following: (a) a 6-minute walk distance (6MWT) of > 30 meters and < 550 meters; (b) a 6MWT of > 150 meters and an EF > 50%; (c) Mayo stage IV and an EF > 50%; (d) Mayo stage IV and 6MWT > 30 meters and < 550 meters; (e) Mayo stage IV and 6MWT > 150 meters and an EF > 50%; (f) having cardiac complications; (g) having Mayo stage IV AL amyloidosis and having cardiac complications; or (h) having Mayo stage IV AL amyloidosis, cardiac complications and 6MWT > 30 meters and < 550 meters.

[0017] In some embodiments, the patient has a 6MWT > 150 meters and an EF > 50%. In some embodiments, the patient has a 6MWT > 30 meters and < 550 meters. In some embodiments, the patient has an EF > 50%. In some embodiments, the patient has a 6MWT > 150 meters. In some embodiments, the patient has cardiac complications. In some embodiments, the patient has Mayo stage IV AL amyloidosis and has cardiac complications. In some embodiments, the patient has Mayo stage IV AL amyloidosis, cardiac complications and a 6MWT > 30 meters and < 550 meters.

[0018] In some embodiments, the patient's NYHA class is reduced by at least 2 classes. In some embodiments, the patient's NYHA class is assessed after 9 months or more of treatment.

[0019] Provided herein is a method of reducing mortality or risk of mortality in a patient with Mayo stage IV AL amyloidosis and having NYHA class III or NYHA class IV, comprising the steps of administering to the patient a therapeutically effective dose of an antibody that competes with 2A4 (ATCC Accession No. PTA-9662) or 7D8 (ATCC Accession No. PTA-9468) for binding to human amyloid A peptide or human kappa or lambda light chain immunoglobulin, or competes with an amount of 11-1F4 (ATCC Accession No. PTA-105) for binding to kappa light chain immunoglobulin; and Also provided is a method comprising administering a therapeutically effective dose of daratumumab to the patient 5 to 90 minutes after completion of the step of administering the antibody, wherein the patient has one or more of the following: (a) a six minute walk distance (6MWT) of > 30 meters and < 550 meters; (b) a 6MWT of > 150 meters and an EF > 50%; (c) Mayo stage IV and an EF > 50%; (d) Mayo stage IV and a 6MWT of > 30 meters and < 550 meters; (e) Mayo stage IV and a 6MWT of > 150 meters and an EF > 50%; (f) having cardiac complications; (g) having Mayo stage IV AL amyloidosis and having cardiac complications; or (h) having Mayo stage IV AL amyloidosis, cardiac complications and a 6MWT of > 30 meters and < 550 meters.

[0020] In some embodiments, the risk of mortality is all-cause mortality. In some embodiments, the risk of mortality is cardiac mortality. In some embodiments, the risk of mortality is assessed 9 months or more after treatment. In some embodiments, the risk of mortality is reduced by at least 15% compared to the risk of mortality in a control population. In some embodiments, the mortality is reduced within 8 months after treatment. In some embodiments, the mortality is reduced within 9 months after treatment. In some embodiments, the mortality is reduced within 10 months after treatment. In some embodiments, the mortality is reduced within 11 months after treatment. In some embodiments, the mortality is reduced within 12 months after treatment.

[0021] In some embodiments, the patient has a 6MWT > 150 meters and an EF > 50%. In some embodiments, the patient has a 6MWT > 30 meters and < 550 meters. In some embodiments, the patient has an EF > 50%. In some embodiments, the patient has a 6MWT > 150 meters. In some embodiments, the patient has cardiac complications. In some embodiments, the patient has Mayo stage IV AL amyloidosis and has cardiac complications. In some embodiments, the patient has Mayo stage IV AL amyloidosis, cardiac complications and a 6MWT > 30 meters and < 550 meters.

[0022] Provided herein is a method of reducing the risk of hospitalization in a patient with Mayo stage IV AL amyloidosis, comprising the steps of administering to the patient a therapeutically effective dose of an antibody that competes with 2A4 (ATCC Accession No. PTA-9662) or 7D8 (ATCC Accession No. PTA-9468) for binding to human amyloid A peptide or human kappa or lambda light chain immunoglobulin, or competes with an amount of 11-1F4 (ATCC Accession No. PTA-105) for binding to kappa light chain immunoglobulin; and ... Also provided is a method comprising administering a therapeutically effective dose of daratumumab to the patient after 90 minutes, wherein the patient has one or more of the following: (a) a 6-minute walk distance (6MWT) of > 30 meters and < 550 meters; (b) a 6MWT of > 150 meters and an EF > 50%; (c) a Mayo stage IV and an EF > 50%; (d) a Mayo stage IV and a 6MWT of > 30 meters and < 550 meters; (e) a Mayo stage IV and a 6MWT of > 150 meters and an EF > 50%; (f) a cardiac complication; (g) a Mayo stage IV AL amyloidosis and a cardiac complication; or (h) a Mayo stage IV AL amyloidosis, a cardiac complication and a 6MWT of > 30 meters and < 550 meters.

[0023] In some embodiments, the risk of hospitalization in the patient is reduced by at least 20% compared to the risk of hospitalization in a control population.

[0024] In some embodiments, the patient has a 6MWT > 150 meters and an EF > 50%. In some embodiments, the patient has a 6MWT > 30 meters and < 550 meters. In some embodiments, the patient has an EF > 50%. In some embodiments, the patient has a 6MWT > 150 meters. In some embodiments, the patient has cardiac complications. In some embodiments, the patient has Mayo stage IV AL amyloidosis and has cardiac complications. In some embodiments, the patient has Mayo stage IV AL amyloidosis, cardiac complications and a 6MWT > 30 meters and < 550 meters.

[0025] Provided herein is a method of increasing the number of days alive out of hospital (DAOH) in a patient with Mayo stage IV amyloidosis, comprising the steps of administering to the patient a therapeutically effective dose of an antibody that competes with 2A4 (ATCC Accession No. PTA-9662) or 7D8 (ATCC Accession No. PTA-9468) for binding to human amyloid A peptide or human kappa or lambda light chain immunoglobulin, or competes with an amount of 11-1F4 (ATCC Accession No. PTA-105) for binding to kappa light chain immunoglobulin; and administering a therapeutically effective dose of daratumumab to the patient 5 to 90 minutes after completion of the step of administering to the patient a therapeutically effective dose of daratumumab, wherein the patient has one or more of the following: (a) a six minute walk distance (6MWT) of > 30 meters and < 550 meters; (b) a 6MWT of > 150 meters and an EF > 50%; (c) Mayo stage IV and an EF > 50%; (d) Mayo stage IV and 6MWT > 30 meters and < 550 meters; (e) Mayo stage IV and 6MWT > 150 meters and an EF > 50%; (f) having cardiac complications; (g) having Mayo stage IV AL amyloidosis and having cardiac complications; or (h) having Mayo stage IV AL amyloidosis, cardiac complications and 6MWT > 30 meters and < 550 meters.

[0026] In some embodiments, the number of DAOH is increased for at least 20 days after one month of treatment compared to a control population. In some embodiments, the number of DAOH is increased for at least 100 days after six months of treatment compared to DAOH in a control population. In some embodiments, the number of DAOH is increased by at least 300 after 12 months of treatment compared to DAOH in a control population. In some embodiments, the number of DAOH is increased by at least 600 after 24 months of treatment compared to DAOH in a control population. In some embodiments, the number of DAOH is increased by at least 900 after 48 months of treatment compared to DAOH in a control population.

[0027] In some embodiments, the patient has a 6MWT > 150 meters and an EF > 50%. In some embodiments, the patient has a 6MWT > 30 meters and < 550 meters. In some embodiments, the patient has an EF > 50%. In some embodiments, the patient has a 6MWT > 150 meters. In some embodiments, the patient has cardiac complications. In some embodiments, the patient has Mayo stage IV AL amyloidosis and has cardiac complications. In some embodiments, the patient has Mayo stage IV AL amyloidosis, cardiac complications, and a 6MWT > 30 meters and < 550 meters.

[0028] Provided herein is a method of reducing NTproBNP levels in a patient with Mayo stage IV AL amyloidosis, comprising the steps of administering to said patient a therapeutically effective dose of an antibody that competes with 2A4 (ATCC Accession No. PTA-9662) or 7D8 (ATCC Accession No. PTA-9468) for binding to human amyloid A peptide or human kappa or lambda light chain immunoglobulin, or competes with an amount of 11-1F4 (ATCC Accession No. PTA-105) for binding to kappa light chain immunoglobulin; and completing the step of administering the antibody. and administering a therapeutically effective dose of daratumumab to the patient 5 to 90 minutes after completion of the procedure, wherein the patient has one or more of the following: (a) a 6-minute walk distance (6MWT) of > 30 meters and < 550 meters; (b) a 6MWT of > 150 meters and an EF > 50%; (c) a Mayo stage IV and an EF > 50%; (d) a Mayo stage IV and a 6MWT of > 30 meters and < 550 meters; (e) a Mayo stage IV and a 6MWT of > 150 meters and an EF > 50%; (f) having a cardiac complication; (g) having Mayo stage IV AL amyloidosis and having a cardiac complication; or (h) having Mayo stage IV AL amyloidosis, a cardiac complication, and a 6MWT of > 30 meters and < 550 meters.

[0029] In some embodiments, the NTproBNP level is reduced by at least 31% from baseline after 3 months of treatment. In some embodiments, the NTproBNP level is reduced by at least 45% from baseline after 3 months of treatment. In some embodiments, the NTproBNP level is reduced by at least 60% from baseline after 3 months of treatment. In some embodiments, the NTproBNP level is reduced by at least 60% from baseline to a nadir >400pg / ml after 3 months of treatment. In some embodiments, the NTproBNP level is reduced to a nadir <400pg / ml after 3 months of treatment. In some embodiments, the NTproBNP level is reduced by at least 45% from baseline after 6 months of treatment. In some embodiments, the NTproBNP level is reduced by at least 60% from baseline to a nadir >400pg / ml after 6 months of treatment. In some embodiments, the NTproBNP level is reduced by at least 60% from baseline to a nadir >400pg / ml after 6 months of treatment. In some embodiments, NTproBNP levels are reduced to a nadir <400 pg / ml after 3 months of treatment.

[0030] In some embodiments, the patient has a 6MWT > 150 meters and an EF > 50%. In some embodiments, the patient has a 6MWT > 30 meters and < 550 meters. In some embodiments, the patient has an EF > 50%. In some embodiments, the patient has a 6MWT > 150 meters. In some embodiments, the patient has cardiac complications. In some embodiments, the patient has Mayo stage IV AL amyloidosis and has cardiac complications. In some embodiments, the patient has Mayo stage IV AL amyloidosis, cardiac complications and a 6MWT > 30 meters and < 550 meters.

[0031] Provided herein is a method of improving cardiac response rates in patients with Mayo stage IV AL amyloidosis, comprising the steps of administering a therapeutically effective amount of an antibody that competes with 2A4 (ATCC Accession No. PTA-9662) or 7D8 (ATCC Accession No. PTA-9468) for binding to human amyloid A peptide or human kappa or lambda light chain immunoglobulin, or competes with an amount of 11-1F4 (ATCC Accession No. PTA-105) for binding to kappa light chain immunoglobulin; and administering a therapeutically effective amount of an antibody that competes with 2A4 (ATCC Accession No. PTA-9662) or 7D8 (ATCC Accession No. PTA-9468) for binding to human amyloid A peptide or human kappa or lambda light chain immunoglobulin; and administering a therapeutically effective amount of an antibody that competes with 2A4 (ATCC Accession No. PTA-9662) or 7D8 (ATCC Accession No. PTA-9468) for binding to kappa ... Also provided are methods that include subsequently administering a therapeutically effective dose of daratumumab to the patient, wherein the patient has one or more of the following: (a) a six minute walk distance (6MWT) of > 30 meters and < 550 meters; (b) a 6MWT of > 150 meters and an EF > 50%; (c) Mayo stage IV and an EF > 50%; (d) Mayo stage IV and a 6MWT of > 30 meters and < 550 meters; (e) Mayo stage IV and a 6MWT of > 150 meters and an EF > 50%; (f) having cardiac complications; (g) having Mayo stage IV AL amyloidosis and having cardiac complications; or (h) having Mayo stage IV AL amyloidosis, cardiac complications and a 6MWT of > 30 meters and < 550 meters.

[0032] In some embodiments, the cardiac response rate is increased by at least 30% after 6 months of treatment compared to baseline. In some embodiments, the cardiac response rate is increased by at least 50% after 12 months of treatment compared to baseline. In some embodiments, the cardiac response rate is increased by at least 75% after 12 months of treatment compared to baseline.

[0033] In some embodiments, the patient has a 6MWT > 150 meters and an EF > 50%. In some embodiments, the patient has a 6MWT > 30 meters and < 550 meters. In some embodiments, the patient has an EF > 50%. In some embodiments, the patient has a 6MWT > 150 meters. In some embodiments, the patient has cardiac complications. In some embodiments, the patient has Mayo stage IV AL amyloidosis and has cardiac complications. In some embodiments, the patient has Mayo stage IV AL amyloidosis, cardiac complications and a 6MWT > 30 meters and < 550 meters.

[0034] Provided herein is a method of improving 6-minute walk distance (6MWT) in patients with Mayo stage IV AL amyloidosis, comprising the steps of administering a therapeutically effective dose of an antibody that competes with 2A4 (ATCC Accession No. PTA-9662) or 7D8 (ATCC Accession No. PTA-9468) for binding to human amyloid A peptide or human kappa or lambda light chain immunoglobulin, or competes with an amount of 11-1F4 (ATCC Accession No. PTA-105) for binding to kappa light chain immunoglobulin; and completing the step of administering the antibody. and administering a therapeutically effective dose of daratumumab to the patient 90 minutes after the first administration of daratumumab to the patient, wherein the patient has one or more of the following: (a) a six minute walk distance (6MWT) of > 30 meters and < 550 meters; (b) a 6MWT of > 150 meters and an EF > 50%; (c) Mayo stage IV and an EF > 50%; (d) Mayo stage IV and 6MWT > 30 meters and < 550 meters; (e) Mayo stage IV and 6MWT > 150 meters and an EF > 50%; (f) having cardiac complications; (g) having Mayo stage IV AL amyloidosis and having cardiac complications; or (h) having Mayo stage IV AL amyloidosis, cardiac complications and 6MWT > 30 meters and < 550 meters.

[0035] In some embodiments, the 6MWT achieved is at least 300 meters. In some embodiments, the 6MWT achieved is at least 300 meters after 3 months of treatment. In some embodiments, the 6MWT achieved is at least 300 meters after 6 months of treatment. In some embodiments, the 6MWT achieved is at least 300 meters after 9 months of treatment. In some embodiments, the 6MWT achieved is at least 300 meters after 12 months of treatment. In some embodiments, the 6MWT achieved is at least 300 meters after 15 months of treatment. In some embodiments, the 6MWT achieved is at least 300 meters after 18 months of treatment.

[0036] In some embodiments, the 6MWT improves by at least 33 meters compared to baseline. In some embodiments, the 6MWT improves by at least 33 meters after 3 months of treatment compared to baseline. In some embodiments, the 6MWT improves by at least 33 meters after 6 months of treatment compared to baseline. In some embodiments, the 6MWT improves by at least 33 meters after 9 months of treatment compared to baseline. In some embodiments, the 6MWT improves by at least 33 meters after 12 months of treatment compared to baseline. In some embodiments, the 6MWT improves by at least 33 meters after 15 months of treatment. In some embodiments, the 6MWT improves by at least 33 meters after 18 months of treatment. In some embodiments, the achieved 6MWT is at least 300 meters after 18 months of treatment. In some embodiments, the 6MWT improves by at least 33 meters after 18 months of treatment compared to baseline.

[0037] In some embodiments, the patient has a 6MWT > 150 meters and an EF > 50%. In some embodiments, the patient has a 6MWT > 30 meters and < 550 meters. In some embodiments, the patient has an EF > 50%. In some embodiments, the patient has a 6MWT > 150 meters. In some embodiments, the patient has cardiac complications. In some embodiments, the patient has Mayo stage IV AL amyloidosis and has cardiac complications. In some embodiments, the patient has Mayo stage IV AL amyloidosis, cardiac complications and a 6MWT > 30 meters and < 550 meters.

[0038] Provided herein is a method of increasing the Kansas City Cardiomyopathy Questionnaire (KCCQ) score in patients with Mayo stage IV AL amyloidosis, comprising the steps of administering a therapeutically effective dose of an antibody that competes with 2A4 (ATCC Accession No. PTA-9662) or 7D8 (ATCC Accession No. PTA-9468) for binding to human amyloid A peptide or human kappa or lambda light chain immunoglobulin, or competes with an amount of 11-1F4 (ATCC Accession No. PTA-105) for binding to kappa light chain immunoglobulin; and administering a therapeutically effective dose of daratumumab to the patient 5 to 90 minutes after completion of the test, wherein the patient has one or more of the following: (a) a 6-minute walk distance (6MWT) of > 30 meters and < 550 meters; (b) a 6MWT of > 150 meters and an EF > 50%; (c) Mayo stage IV and an EF > 50%; (d) Mayo stage IV and 6MWT > 30 meters and < 550 meters; (e) Mayo stage IV and 6MWT > 150 meters and an EF > 50%; (f) having cardiac complications; (g) having Mayo stage IV AL amyloidosis and having cardiac complications; or (h) having Mayo stage IV AL amyloidosis, cardiac complications and 6MWT > 30 meters and < 550 meters.

[0039] In some embodiments, the KCCQ score is increased by at least 5 after 3 months of treatment compared to baseline. In some embodiments, the KCCQ score is increased by at least 10 after 3 months of treatment compared to baseline. In some embodiments, the KCCQ score is increased by at least 15 after 3 months of treatment compared to baseline. In some embodiments, the KCCQ score improves by at least 20 after 3 months of treatment compared to baseline. In some embodiments, the KCCQ score improves by at least 5 after 12 months of treatment compared to baseline. In some embodiments, the KCCQ score improves by at least 10 after 12 months of treatment compared to baseline. In some embodiments, the KCCQ score improves by at least 15 after 12 months of treatment compared to baseline. In some embodiments, the KCCQ score improves by at least 20 after 12 months of treatment compared to baseline.

[0040] In some embodiments, the patient has a 6MWT > 150 meters and an EF > 50%. In some embodiments, the patient has a 6MWT > 30 meters and < 550 meters. In some embodiments, the patient has an EF > 50%. In some embodiments, the patient has a 6MWT > 150 meters. In some embodiments, the patient has cardiac complications. In some embodiments, the patient has Mayo stage IV AL amyloidosis and has cardiac complications. In some embodiments, the patient has Mayo stage IV AL amyloidosis, cardiac complications and a 6MWT > 30 meters and < 550 meters.

[0041] Provided herein is a method of increasing major organ progression-free survival in patients with Mayo stage IV AL amyloidosis, comprising the steps of administering to the patient a therapeutically effective dose of an antibody that competes with 2A4 (ATCC Accession No. PTA-9662) or 7D8 (ATCC Accession No. PTA-9468) for binding to human amyloid A peptide or human kappa or lambda light chain immunoglobulin, or competes with an amount of 11-1F4 (ATCC Accession No. PTA-105) for binding to kappa light chain immunoglobulin; and completing the step of administering the antibody. Also provided is a method comprising administering a therapeutically effective dose of daratumumab to the patient 5 to 90 minutes later, wherein the patient has one or more of the following: (a) a 6-minute walk distance (6MWT) of > 30 meters and < 550 meters; (b) a 6MWT of > 150 meters and an EF > 50%; (c) a Mayo stage IV and an EF > 50%; (d) a Mayo stage IV and a 6MWT of > 30 meters and < 550 meters; (e) a Mayo stage IV and a 6MWT of > 150 meters and an EF > 50%; (f) a cardiac complication; (g) a Mayo stage IV AL amyloidosis and a cardiac complication; or (h) a Mayo stage IV AL amyloidosis, a cardiac complication and a 6MWT of > 30 meters and < 550 meters.

[0042] In some embodiments, the NTproBNP level is reduced by at least 31% from baseline after 3 months of treatment. In some embodiments, the NTproBNP level is reduced by at least 45% from baseline after 3 months of treatment. In some embodiments, the NTproBNP level is reduced by at least 60% from baseline after 3 months of treatment. In some embodiments, the NTproBNP level is reduced by at least 60% from baseline to a nadir >400pg / ml after 3 months of treatment. In some embodiments, the NTproBNP level is reduced to a nadir <400pg / ml after 3 months of treatment. In some embodiments, the NTproBNP level is reduced by at least 45% from baseline after 6 months of treatment. In some embodiments, the NTproBNP level is reduced by at least 60% from baseline to a nadir >400pg / ml after 6 months of treatment. In some embodiments, the NTproBNP level is reduced by at least 60% from baseline to a nadir >400pg / ml after 6 months of treatment. In some embodiments, NTproBNP levels are reduced to a nadir <400 pg / ml after 3 months of treatment.

[0043] In some embodiments, the patient has a 6MWT > 150 meters and an EF > 50%. In some embodiments, the patient has a 6MWT > 30 meters and < 550 meters. In some embodiments, the patient has an EF > 50%. In some embodiments, the patient has a 6MWT > 150 meters. In some embodiments, the patient has cardiac complications. In some embodiments, the patient has Mayo stage IV AL amyloidosis and has cardiac complications. In some embodiments, the patient has Mayo stage IV AL amyloidosis, cardiac complications and a 6MWT > 30 meters and < 550 meters.

[0044] Provided herein is a method of treating a patient with AL amyloidosis, comprising the steps of: (a) determining that the patient has a 6-minute walk distance (6MWT) of ≥ 30 meters and ≤ 550 meters, or a 6MWT of ≥ 150 meters, and / or an ejection fraction (EF) > 50%; (b) selecting the patient for treatment with human amyloid A peptide or an antibody that competes with 2A4 (ATCC Accession No. PTA-9662) or 7D8 (ATCC Accession No. PTA-9468) for binding to human kappa or lambda light chain immunoglobulin, or competes with 11-1F4 (ATCC Accession No. PTA-105) for binding to kappa light chain immunoglobulin, and daratumumab; (c) administering an effective dosage of the antibody to the selected patient; and (d) administering a therapeutically effective amount of daratumumab to the selected patient 5 to 90 minutes after completion of the step of administering the antibody, wherein the patient is: (a) Mayo stage IV Also provided are methods for treating AL amyloidosis, the method comprising the steps of: (a) having one or more of: (b) a six minute walk distance (6MWT) of > 30 meters and < 550 meters; (c) a 6MWT of > 150 meters and an EF > 50%; (d) Mayo stage IV and an EF > 50%; (e) Mayo stage IV and a 6MWT of > 30 meters and < 550 meters; (f) Mayo stage IV and a 6MWT of > 150 meters and an EF > 50%; (g) having cardiac complications; (h) having Mayo stage IV AL amyloidosis and having cardiac complications; or (i) having Mayo stage IV AL amyloidosis, cardiac complications and a 6MWT of > 30 meters and < 550 meters.

[0045] In some embodiments, the patient has Mayo stage IV AL amyloidosis. In some embodiments, the patient has 6MWT > 150 meters and EF > 50%. In some embodiments, the patient has 6MWT > 30 meters and ≦ 550 meters. In some embodiments, the patient has EF > 50%. In some embodiments, the patient has 6MWT > 150 meters. In some embodiments, the patient has cardiac complications. In some embodiments, the patient has Mayo stage IV AL amyloidosis and cardiac complications. In some embodiments, the patient has Mayo stage IV AL amyloidosis, cardiac complications, and 6MWT > 30 meters and ≦ 550 meters.

[0046] Provided herein is a method of treating a patient with AL amyloidosis who has demonstrated a 6-minute walk distance (6MWT) of ≧30 meters and ≦550 meters, or a 6MWT of greater than or equal to 150 meters and / or an ejection fraction (EF) of greater than 50%, comprising the steps of administering to the patient an effective dose of daratumumab and an antibody that competes with 2A4 (ATCC Accession No. PTA-9662) or 7D8 (ATCC Accession No. PTA-9468) for binding to human amyloid A peptide or human kappa or lambda light chain immunoglobulin, or competes with 11-1F4 (ATCC Accession No. PTA-105) for binding to kappa light chain immunoglobulin; and administering to the patient a therapeutically effective amount of daratumumab 5 to 90 minutes after completion of the step of administering the antibody, wherein the patient is: (a) in a state of Mayo stage IV or later; Also provided are methods for treating AL amyloidosis, the method comprising the steps of: (a) having one or more of: (b) a six minute walk distance (6MWT) of > 30 meters and < 550 meters; (c) a 6MWT of > 150 meters and an EF > 50%; (d) Mayo stage IV and an EF > 50%; (e) Mayo stage IV and a 6MWT of > 30 meters and < 550 meters; (f) Mayo stage IV and a 6MWT of > 150 meters and an EF > 50%; (g) having cardiac complications; (h) having Mayo stage IV AL amyloidosis and having cardiac complications; or (i) having Mayo stage IV AL amyloidosis, cardiac complications and a 6MWT of > 30 meters and < 550 meters.

[0047] In some embodiments, the patient has Mayo stage IV AL amyloidosis. In some embodiments, the patient has 6MWT > 150 meters and EF > 50%. In some embodiments, the patient has 6MWT > 30 meters and ≦ 550 meters. In some embodiments, the patient has EF > 50%. In some embodiments, the patient has 6MWT > 150 meters. In some embodiments, the patient has cardiac complications. In some embodiments, the patient has Mayo stage IV AL amyloidosis and cardiac complications. In some embodiments, the patient has Mayo stage IV AL amyloidosis, cardiac complications, and 6MWT > 30 meters and ≦ 550 meters.

[0048] Provided herein is a method of reducing the risk of mortality by at least 45% in a patient with AL amyloidosis, comprising the steps of administering to the patient an effective dose of an antibody that competes with 2A4 (ATCC Accession No. PTA-9662) or 7D8 (ATCC Accession No. PTA-9468) for binding to human amyloid A peptide or human kappa or lambda light chain immunoglobulin, or competes with 11-1F4 (ATCC Accession No. PTA-105), 6MWT for binding to kappa light chain immunoglobulin, and daratumumab; and administering to the patient a therapeutically effective amount of daratumumab 5 to 90 minutes after completion of the step of administering the antibody, wherein the patient is: (a) in a state of Mayo stage IV or later; Also provided are methods for treating AL amyloidosis, the method comprising the steps of: (a) having one or more of: (b) a six minute walk distance (6MWT) of > 30 meters and < 550 meters; (c) a 6MWT of > 150 meters and an EF > 50%; (d) Mayo stage IV and an EF > 50%; (e) Mayo stage IV and a 6MWT of > 30 meters and < 550 meters; (f) Mayo stage IV and a 6MWT of > 150 meters and an EF > 50%; (g) having cardiac complications; (h) having Mayo stage IV AL amyloidosis and having cardiac complications; or (i) having Mayo stage IV AL amyloidosis, cardiac complications and a 6MWT of > 30 meters and < 550 meters.

[0049] In some embodiments, the risk of mortality is a risk of all-cause mortality. In some embodiments, the risk of all-cause mortality is reduced by at least about 48.9%. In some embodiments, the risk of all-cause mortality is reduced by at least about 50%. In some embodiments, the risk of all-cause mortality is reduced by at least about 50.2%. In some embodiments, the risk of all-cause mortality is reduced by at least about 60%. In some embodiments, the risk of all-cause mortality is reduced by at least about 70%. In some embodiments, the risk of all-cause mortality is reduced by at least about 79.9%. In some embodiments, the risk of all-cause mortality is reduced by at least about 81.5%.

[0050] In some embodiments, the risk of mortality is a risk of cardiac mortality. In some embodiments, the risk of cardiac mortality is reduced by at least about 75%. In some embodiments, the risk of cardiac mortality is reduced by at least about 62.2%.

[0051] In some embodiments, the patient has Mayo stage IV AL amyloidosis. In some embodiments, the patient has 6MWT > 150 meters and EF > 50%. In some embodiments, the patient has 6MWT > 30 meters and ≦ 550 meters. In some embodiments, the patient has EF > 50%. In some embodiments, the patient has 6MWT > 150 meters. In some embodiments, the selected patient has cardiac complications. In some embodiments, the selected patient has Mayo stage IV AL amyloidosis and cardiac complications. In some embodiments, the selected patient has Mayo stage IV AL amyloidosis, cardiac complications, and 6MWT > 30 meters and ≦ 550 meters.

[0052] Provided herein is a method of reducing longitudinal global strain (GLS) in a patient with AL amyloidosis, comprising the steps of administering to a selected patient an effective dose of an antibody that competes with 2A4 (ATCC Accession No. PTA-9662) or 7D8 (ATCC Accession No. PTA-9468) for binding to human amyloid A peptide or human kappa or lambda light chain immunoglobulin, or competes with 11-1F4 (ATCC Accession No. PTA-105), 6MWT for binding to kappa light chain immunoglobulin, and daratumumab; and administering to the patient a therapeutically effective amount of daratumumab 5 to 90 minutes after completion of the step of administering the antibody, wherein the patient is: (a) at least one of the following: (i) at least one of the following: (a) at least one of the following: (i) at least one of the following: (a) at least one of the following: (b) at least one of the following: (c) at least one of the following: (d) at least one of the following: (a) at least one of the following: (i) at least one of the following: (a) at least one of the following: (b) at least one of the following: (c ... Also provided are methods for treating AL amyloidosis, the method comprising the steps of: (a) having one or more of: (b) a six minute walk distance (6MWT) of > 30 meters and < 550 meters; (c) a 6MWT of > 150 meters and an EF > 50%; (d) Mayo stage IV and an EF > 50%; (e) Mayo stage IV and a 6MWT of > 30 meters and < 550 meters; (f) Mayo stage IV and a 6MWT of > 150 meters and an EF > 50%; (g) having cardiac complications; (h) having Mayo stage IV AL amyloidosis and having cardiac complications; or (i) having Mayo stage IV AL amyloidosis, cardiac complications and a 6MWT of > 30 meters and < 550 meters.

[0053] In some embodiments, the administering step results in a reduction in GLS in the patient of about 0.1% to about 10%. In some embodiments, the administering step results in a reduction in GLS in the human subject of about 0.5% to about 10%. In some embodiments, the administering step results in a reduction in GLS in the human subject of about 1% to about 10%. In some embodiments, the administering step results in a reduction in GLS in the human subject of at least about 0.5%. In some embodiments, the administering step results in a reduction in GLS in the human subject of at least about 1.0%. In some embodiments, the administering step results in a reduction in GLS in the human subject of at least about 2.0%. In some embodiments, the administering step results in a reduction in GLS in the human subject of at least about 10%.

[0054] In some embodiments, the patient has Mayo stage IV AL amyloidosis. In some embodiments, the patient has 6MWT > 150 meters and EF > 50%. In some embodiments, the patient has 6MWT > 30 meters and ≦ 550 meters. In some embodiments, the patient has EF > 50%. In some embodiments, the patient has 6MWT > 150 meters. In some embodiments, the patient has cardiac complications. In some embodiments, the patient has Mayo stage IV AL amyloidosis and cardiac complications. In some embodiments, the patient has Mayo stage IV AL amyloidosis, cardiac complications, and 6MWT > 30 meters and ≦ 550 meters.

[0055] Provided herein is a method of improving the Short 36-Item Physical Component Score (SF-36PCS) in patients with AL amyloidosis, comprising the steps of administering to the patient an effective dose of an antibody that competes with 2A4 (ATCC Accession No. PTA-9662) or 7D8 (ATCC Accession No. PTA-9468) for binding to human amyloid A peptide or human kappa or lambda light chain immunoglobulin, or competes with 11-1F4 (ATCC Accession No. PTA-105) for binding to kappa light chain immunoglobulin, and daratumumab; and administering to the patient a therapeutically effective amount of daratumumab 5 to 90 minutes after completion of the step of administering the antibody, wherein the SF-36v2 score is determined at least one month after treatment, and the patient is: (a) Mayo stage IV Also provided are methods for treating AL amyloidosis, the method comprising the steps of: (a) having one or more of: (b) a six minute walk distance (6MWT) of > 30 meters and < 550 meters; (c) a 6MWT of > 150 meters and an EF > 50%; (d) Mayo stage IV and an EF > 50%; (e) Mayo stage IV and a 6MWT of > 30 meters and < 550 meters; (f) Mayo stage IV and a 6MWT of > 150 meters and an EF > 50%; (g) having cardiac complications; (h) having Mayo stage IV AL amyloidosis and having cardiac complications; or (i) having Mayo stage IV AL amyloidosis, cardiac complications and a 6MWT of > 30 meters and < 550 meters.

[0056] In some embodiments, the duration of treatment is effective to achieve or maintain at least about a 5-point increase from baseline in SF-36v2. In some embodiments, the SF-36v2 PCS score is determined after 2 months of treatment. In some embodiments, the SF-36v2 PCS score is determined after 3 months of treatment. In some embodiments, the SF-36v2 PCS score is determined after 6 months of treatment. In some embodiments, the SF-36v2 PCS score is determined after 9 months of treatment. In some embodiments, the SF-36v2 PCS score is determined after 12 months of treatment.

[0057] In some embodiments, the patient has Mayo stage IV AL amyloidosis. In some embodiments, the patient has 6MWT > 150 meters and EF > 50%. In some embodiments, the patient has 6MWT > 30 meters and ≦ 550 meters. In some embodiments, the patient has EF > 50%. In some embodiments, the patient has 6MWT > 150 meters. In some embodiments, the patient has cardiac complications. In some embodiments, the patient has Mayo stage IV AL amyloidosis and cardiac complications. In some embodiments, the patient has Mayo stage IV AL amyloidosis, cardiac complications, and 6MWT > 30 meters and ≦ 550 meters.

[0058] Also provided herein is a method of reducing mortality or risk of mortality in a patient with Mayo stage IV AL amyloidosis, comprising administering to the patient an effective dosage of an antibody that competes with 2A4 (ATCC Accession No. PTA-9662) or 7D8 (ATCC Accession No. PTA-9468) for binding to human amyloid A peptide or human kappa or lambda light chain immunoglobulin, or that competes with 11-1F4 (ATCC Accession No. PTA-105) for binding to kappa light chain immunoglobulin; administering to the patient a therapeutically effective dosage of daratumumab 5 to 90 minutes after completion of the step of administering the antibody.

[0059] In some embodiments, the risk of mortality is all-cause mortality, hi some embodiments, the risk of mortality is cardiac mortality.

[0060] In some embodiments, the risk of mortality is reduced after 1 month of treatment. In some embodiments, the risk of mortality is reduced after 2 months of treatment. In some embodiments, the risk of mortality is reduced after 3 months of treatment. In some embodiments, the risk of mortality is reduced after 4 months of treatment. In some embodiments, the risk of mortality is reduced after 5 months of treatment. In some embodiments, the risk of mortality is reduced after 6 months of treatment. In some embodiments, the risk of mortality is reduced after 7 months of treatment. In some embodiments, the risk of mortality is reduced after 8 months of treatment. In some embodiments, the risk of mortality is reduced after 9 months of treatment. In some embodiments, the risk of mortality is reduced after 10 months of treatment. In some embodiments, the risk of mortality is reduced after 11 months of treatment. In some embodiments, the risk of mortality is reduced after 12 months of treatment.

[0061] In some embodiments, the risk of mortality is reduced by at least 15% compared to the risk of mortality in a control population.

[0062] In some embodiments, the patient has a 6MWT > 150 meters and an EF > 50%. In some embodiments, the patient has a 6MWT > 30 meters and < 550 meters. In some embodiments, the patient has an EF > 50%. In some embodiments, the patient has a 6MWT > 150 meters. In some embodiments, the patient has cardiac complications. In some embodiments, the patient has Mayo stage IV AL amyloidosis and has cardiac complications. In some embodiments, the patient has Mayo stage IV AL amyloidosis, cardiac complications and a 6MWT > 30 meters and < 550 meters.

[0063] Also provided herein is a method of reducing global longitudinal strain (GLS) in a patient with Mayo stage IV AL amyloidosis, comprising administering to the patient an effective dosage of an antibody that competes with 2A4 (ATCC Accession No. PTA-9662) or 7D8 (ATCC Accession No. PTA-9468) for binding to human amyloid A peptide or human kappa or lambda light chain immunoglobulin, or that competes with 11-1F4 (ATCC Accession No. PTA-105) for binding to kappa light chain immunoglobulin.

[0064] In some embodiments, the administering step results in a reduction in GLS in the patient of about 0.1% to about 10%. In some embodiments, the administering step results in a reduction in GLS in the human subject of about 0.5% to about 10%. In some embodiments, the administering step results in a reduction in GLS in the human subject of about 1% to about 10%. In some embodiments, the administering step results in a reduction in GLS in the human subject of at least about 0.5%. In some embodiments, the administering step results in a reduction in GLS in the human subject of at least about 1.0%. In some embodiments, the administering step results in a reduction in GLS in the human subject of at least about 2.0%. In some embodiments, the administering step results in a reduction in GLS in the human subject of at least about 10%.

[0065] In some embodiments, the patient has a 6MWT > 150 meters and an EF > 50%. In some embodiments, the patient has a 6MWT > 30 meters and < 550 meters. In some embodiments, the patient has an EF > 50%. In some embodiments, the patient has a 6MWT > 150 meters. In some embodiments, the patient has cardiac complications. In some embodiments, the patient has Mayo stage IV AL amyloidosis and has cardiac complications. In some embodiments, the patient has Mayo stage IV AL amyloidosis, cardiac complications and a 6MWT > 30 meters and < 550 meters.

[0066] Also provided herein is a method of reducing global longitudinal strain (GLS) in a patient with Mayo stage IV AL amyloidosis, comprising administering to the patient an effective dosage of an antibody that competes with 2A4 (ATCC Accession No. PTA-9662) or 7D8 (ATCC Accession No. PTA-9468) for binding to human amyloid A peptide or human kappa or lambda light chain immunoglobulin, or that competes with 11-1F4 (ATCC Accession No. PTA-105) for binding to kappa light chain immunoglobulin; and administering to the patient a therapeutically effective dosage of daratumumab 5 to 90 minutes after completion of the step of administering the antibody.

[0067] In some embodiments, the administering step results in a reduction in GLS in the patient of about 0.1% to about 10%. In some embodiments, the administering step results in a reduction in GLS in the human subject of about 0.5% to about 10%. In some embodiments, the administering step results in a reduction in GLS in the human subject of about 1% to about 10%. In some embodiments, the administering step results in a reduction in GLS in the human subject of at least about 0.5%. In some embodiments, the administering step results in a reduction in GLS in the human subject of at least about 1.0%. In some embodiments, the administering step results in a reduction in GLS in the human subject of at least about 2.0%. In some embodiments, the administering step results in a reduction in GLS in the human subject of at least about 10%.

[0068] In some embodiments, the patient has a 6MWT > 150 meters and an EF > 50%. In some embodiments, the patient has a 6MWT > 30 meters and < 550 meters. In some embodiments, the patient has an EF > 50%. In some embodiments, the patient has a 6MWT > 150 meters. In some embodiments, the patient has cardiac complications. In some embodiments, the patient has Mayo stage IV AL amyloidosis and has cardiac complications. In some embodiments, the patient has Mayo stage IV AL amyloidosis, cardiac complications and a 6MWT > 30 meters and < 550 meters.

[0069] Also provided herein is a method of treating a patient having AL amyloidosis, the method comprising administering to the patient an effective dosage of an antibody that competes with 2A4 (ATCC Accession No. PTA-9662) or 7D8 (ATCC Accession No. PTA-9468) for binding to human amyloid A peptide or human kappa or lambda light chain immunoglobulin, or that competes with 11-1F4 (ATCC Accession No. PTA-105) for binding to kappa light chain immunoglobulin; and administering to the patient a therapeutically effective dosage of daratumumab 5 to 90 minutes after completion of the step of administering the antibody, wherein the patient has (a) Mayo stage IV AL amyloidosis.

[0070] In some embodiments, the patient has a 6MWT > 150 meters and an EF > 50%. In some embodiments, the patient has a 6MWT > 30 meters and ≦ 550 meters. In some embodiments, the patient has an EF > 50%. In some embodiments, the patient has a 6MWT > 150 meters. In some embodiments, the selected patient has a cardiac complication. In some embodiments, the selected patient has Mayo stage IV AL amyloidosis and has a cardiac complication. In some embodiments, the selected patient has Mayo stage IV AL amyloidosis, a cardiac complication, and a 6MWT > 30 meters and ≦ 550 meters. In some embodiments, the therapeutically effective dose of daratumumab to the patient is administered approximately 60 minutes after completion of administration of the antibody.

[0071] In some embodiments, the antibody comprises a light chain variable region comprising the three complementarity determining regions set forth as SEQ ID NO:3, 4 and 5 or SEQ ID NO:16, 17 and 18, and a heavy chain variable region comprising the three complementarity determining regions set forth as SEQ ID NO:6, 7 and 8 or SEQ ID NO:19, 20 and 21. In some embodiments, the light chain variable region comprises the amino acid sequence set forth as SEQ ID NO:1 or 14. In some embodiments, the heavy chain variable region comprises the amino acid sequence set forth as SEQ ID NO:2 or 15. In some embodiments, the light chain variable region comprises the amino acid sequence set forth as SEQ ID NO:1 or 14, and the heavy chain variable region comprises the amino acid sequence set forth as SEQ ID NO:2 or 15. In some embodiments, the antibody comprises a light chain comprising the amino acid sequence set forth as SEQ ID NO:10, and a heavy chain comprising the amino acid sequence set forth as SEQ ID NO:11, 12 or 13. In some embodiments, the antibody comprises a light chain comprising the amino acid sequence set forth as SEQ ID NO:10, and a heavy chain comprising the amino acid sequence set forth as SEQ ID NO:12.

[0072] In some embodiments, the patient has previously undergone or has concurrently undergone treatment with melphalan, prednisone, dexamethasone, bortezomib, cyclophosphamide, lenalidomide, doxorubicin, or combinations thereof.

[0073] In some embodiments, the antibody comprises a light chain variable region comprising the three complementarity determining regions of 2A4, 7D8 or 11-1F4, and a heavy chain variable region comprising the three complementarity determining regions of 2A4, 7D8 or 11-1F4, respectively. In some embodiments, the antibody is a humanized version of 2A4. In some embodiments, the antibody is a humanized or chimeric version of 11-1F4. In some embodiments, the antibody is viltamimab.

[0074] In some embodiments, the patient shows improvement in the 36-Item Short Form Survey Physical Component Score (SF-36PCS) or SF-36v2 after treatment with the antibody. In some embodiments, after 9 months of treatment, the change in the patient's score on the SF-36PCS or SF-36v2 is at least 5 points higher than a different patient who has not received the antibody at the same time point.

[0075] In some embodiments, a therapeutically effective dose of the antibody is administered from a pharmaceutical formulation comprising the antibody at a concentration within the range of about 1 mg / mL to about 100 mg / mL. In some embodiments, a therapeutically effective dose of the antibody is from about 0.5 mg / kg to about 30 mg / kg, and the antibody is administered intravenously or subcutaneously at a frequency of about weekly to about four times a year. In some embodiments, a therapeutically effective dose of the antibody is present at a concentration of about 50 mg / mL.

[0076] In some embodiments, the therapeutically effective dose is administered intravenously after transferring the amount of formulation required for the dose from the vial to an intravenous bag containing the liquid, hi some embodiments, the therapeutically effective dose is about 24 mg / kg and the antibody is administered intravenously every 28 days.

[0077] In some embodiments, the duration of treatment is at least 15 months. In some embodiments, the duration of treatment is at least 12 months. In some embodiments, the duration of treatment is at least 9 months. In some embodiments, the duration of treatment is at least 6 months. In some embodiments, the duration of treatment is at least 3 months.

[0078] In some embodiments, the duration is effective to achieve or maintain at least about a 3 point increase from baseline in the SF-36PCS or SF-36v2.

[0079] In some embodiments, the antibody is a Fab, Fab', F(ab')2, F(ab)c, Dab, Nanobody or Fv.

[0080] In some embodiments, treatment results in a 20% relative reduction in hospitalizations. In some embodiments, treatment results in a 31%-60% reduction in NTproBNP from baseline. In some embodiments, treatment results in a >60% reduction in NTproBNP levels from baseline to a nadir NTproBNP >400 pg / mL. In some embodiments, treatment results in a nadir NTproBNP level of <400 pg / mL.

[0081] In some embodiments, treatment results in at least a 5 point change to a 20 point change in the Kansas City Cardiomyopathy Questionnaire (KCCQ) score.

[0082] In some embodiments, after 3 months of treatment, there is at least a 33 meter improvement in the 6MWT. In some embodiments, after 6 months of treatment, there is at least a 33 meter improvement in the 6MWT. In some embodiments, after 9 months of treatment, there is at least a 33 meter improvement in the 6MWT. In some embodiments, after 12 months of treatment, there is at least a 33 meter improvement in the 6MWT. In some embodiments, after 15 months of treatment, there is at least a 33 meter improvement in the 6MWT. In some embodiments, after 18 months of treatment, there is at least a 33 meter improvement in the 6MWT.

[0083] In some embodiments, if the patient has an NTproBNP level > 8500 pg / mL, the patient is excluded from receiving the treatment.

[0084] In some embodiments, the patient has not undergone an autologous transplant prior to administration of the effective dose of the antibody, hi some embodiments, the patient is unable to undergo an autologous transplant during treatment.

[0085] In some embodiments, daratumumab is administered 120 minutes after the completion of the step of administering the antibody. In some embodiments, daratumumab is administered 90 minutes after the completion of the step of administering the antibody. In some embodiments, daratumumab is administered 75 minutes after the completion of the step of administering the antibody. In some embodiments, daratumumab is administered 60 minutes after the completion of the step of administering the antibody. In some embodiments, daratumumab is administered 30 minutes after the completion of the step of administering the antibody. In some embodiments, daratumumab is administered 15 minutes after the completion of the step of administering the antibody. In some embodiments, daratumumab is administered 5 minutes after the completion of the step of administering the antibody.

[0086] In some embodiments, patients meet the following criteria: (i) previously described or currently documented clinical signs and symptoms supporting a diagnosis of heart failure in the setting of a definitive diagnosis of AL amyloidosis in the absence of any other possible explanation for heart failure; and (ii) an echocardiogram demonstrating a mean left ventricular wall thickness in diastolic >12 mm in the absence of an endomyocardial biopsy or other cause demonstrating AL amyloidosis. In some embodiments, the other cause includes severe hypertension or aortic stenosis. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0087] Detailed Description The present disclosure provides a method for treating certain AL amyloidosis patients, i.e., patients with Mayo stage IV AL amyloidosis.In some embodiments, the Mayo stage IV AL amyloidosis patients have a baseline 6-minute walk distance (6MWT; may be referred to as 6-minute walk test (6MWT) distance) greater than or equal to 150 meters, and have a baseline EF greater than 50%, the Mayo stage IV patients have a baseline 6MWT greater than or equal to 150 meters and an ejection fraction (EF) greater than 50%, have cardiac complications; have Mayo stage IV AL amyloidosis and have cardiac complications; and / or have Mayo stage IV AL amyloidosis, cardiac complications and 6MWT≧30 meters and≦550 meters.In some embodiments, the patients have an ejection fraction greater than 50%. The method includes administering to such patient an antibody that competes with antibody 2A4 (ATCC Accession No. PTA-9662) or antibody 7D8 (ATCC Accession No. PTA-9468) for binding to human amyloid A peptide or human kappa or lambda light chain immunoglobulin, or that competes with antibody 11-1F4 (ATCC Accession No. PTA-105) for binding of its light chain to kappa immunoglobulin, and administering to the patient a therapeutically effective dose of daratumumab 5 to 90 minutes after administering the antibody, wherein the patient has Mayo stage IV AL amyloidosis. Patients with Mayo stage IV amyloidosis may have: 6MWT > 30 meters and < 550 meters; 6MWT > 150 meters and EF > 50% at baseline; Mayo stage IV and 6MWT > 30 meters and < 550 meters; Mayo stage IV and EF > 50% at baseline; Mayo stage IV, 6MWT > 150 meters and EF > 50% at baseline; with cardiac complications; Mayo stage IV AL amyloidosis and cardiac complications; or Mayo stage IV AL amyloidosis, cardiac complications and 6MWT > 30 meters and < 550 meters. In some embodiments, the antibody is virutamimab.

[0088] I. Definition The term "antibody" includes intact antibodies and antigen-binding fragments thereof. Typically, fragments compete with the intact antibody from which they are derived for specific binding to a target and include separated heavy and light chains Fab, Fab', F(ab')2, F(ab)c, Dab, nanobody and Fv. Fragments may be produced by recombinant DNA techniques or by enzymatic or chemical separation of intact immunoglobulins. The term "antibody" also includes bispecific or multispecific antibodies and / or humanized antibodies. Bispecific or bifunctional or multifunctional antibodies are artificial hybrid antibodies having two or more different heavy / light chain pairs and two or more different binding sites (see, for example, Songsivilai and Lachmann, Clin. Exp. Immunol., 79:315-321 (1990); Kostelny et al., J. Immunol., 148:1547-53 (1992)).

[0089] The term "baseline" includes an initial measurement of a condition (e.g., a score described herein, a response to treatment, etc., as measured by a test or other described measurement technique) obtained at an early time point and used for comparison over time to look for changes and for comparison with later data.

[0090] The term "censored" refers to a situation in which the value of a measurement or observation is only partially known. For example, if a study is conducted to measure the effect of a drug on mortality, patients who discontinue the study are considered to have survived throughout the duration of the study, regardless of their unknown fate (i.e., alive or dead), and survival is estimated for the period of the study where data indicating mortality are missing.

[0091] The term "control population" or "control group" includes a population or group of patients who can receive a placebo, another treatment, or no drug or treatment (e.g., treatment with any of the antibodies described herein). Patients receiving treatment can be compared to a control population or group.

[0092] The term "cardiac complications" refers to either previously described or currently documented clinical signs and symptoms that support a diagnosis of heart failure in the context of a definitive diagnosis of AL amyloidosis in the absence of any other possible explanation for heart failure, and an endomyocardial biopsy demonstrating AL amyloidosis or an echocardiogram demonstrating a mean left ventricular wall thickness >12 mm in diastolic time that would adequately describe the degree of wall thickening in the absence of other causes (e.g., severe hypertension, aortic stenosis).

[0093] The term "ejection fraction" or "EF" refers to a measurement of how much blood the left ventricle pumps out with each contraction. An ejection fraction of 50 percent means that 50 percent of the total volume of blood in the left ventricle is pushed out with each heartbeat. Ejection fraction is used as a measurement of heart failure. The EF of a normal heart is typically between 50 and 70 percent. 41 to 49 percent is considered borderline, and an EF below 40 percent may be evidence of heart failure or cardiomyopathy.

[0094] The term "hazard ratio" or "HR" reflects the instantaneous probability of an event (death or progression) in the experimental arm as a ratio to the likelihood in the comparison arm (i.e., hazard rate). When the HR is 1.0, there is no clear advantage to either arm. The lower the HR value, the greater the reduction in risk of death or progression for the experimental treatment arm of the study, calculated as 1-HR. For example, an HR of 0.84 is equivalent to a 16% relative reduction in event risk compared to the control arm of the study.

[0095] The term "humanized immunoglobulin" or "humanized antibody" refers to an immunoglobulin or antibody that comprises at least one humanized immunoglobulin or antibody chain (i.e., at least one humanized light or heavy chain). The term "humanized immunoglobulin chain" or "humanized antibody chain" (i.e., "humanized immunoglobulin light chain" or "humanized immunoglobulin heavy chain") refers to an immunoglobulin or antibody chain (i.e., light or heavy chain, respectively) that has a variable region that comprises a variable framework region substantially derived from a human immunoglobulin or antibody and a complementarity determining region (CDR) substantially derived from a non-human immunoglobulin or antibody (e.g., at least one CDR, preferably two CDRs, more preferably three CDRs), and further comprises a constant region (e.g., at least one constant region or portion thereof in the case of a light chain, and preferably three constant regions in the case of a heavy chain). The term "humanized variable region" (e.g., "humanized light chain variable region" or "humanized heavy chain variable region") refers to a variable region comprising a variable framework region substantially derived from a human immunoglobulin or antibody and complementarity determining regions (CDRs) substantially derived from a non-human immunoglobulin or antibody.

[0096] The term "Mayo stage IV patient" or "stage IV" refers to a patient with stage IV disease according to the prognostic staging system established by the Mayo Clinic (Kumar et al., Revised Prognostic Staging System for Light Chain Amyloidosis Incorporating Cardiac Biomarkers and Serum Free Light Chain Measurements, J Clin Oncol 30:989-995 2012), which incorporates both cardiac biomarkers and levels of amyloidogenic light chain synthesis. Collectively, patients with stage I, stage II, or stage III disease are referred to herein as "Mayo stage I-III patients" or "stage I-III patients." In some embodiments, patients are identified as having stage IV AL amyloidosis if they meet the criteria for the following three prognostic variables: troponin-T (cTnT) > ​​0.025ng / mL, N-terminal pro-B-type natriuretic peptide (NT-ProBNP) > 1,800pg / mL, and difference between involved and uninvolved light chains (FLC-diff or dFLC) > 18mg / dL. In certain embodiments, patients may be identified as Mayo stage IV as defined by: (1) NT-proBNP > 1800pg / mL, (2) troponin-T > 0.03ng / mL, and (3) dFLC > 18mg / dL.

[0097] The term "p-value" or "p" refers to a number between 0 and 1 that relates to the significance of the results obtained. A small p-value indicates strong evidence against the null hypothesis (i.e., that there is no effect), e.g., ≦0.1 indicates statistical significance, and p≦0.001 is even more statistically significant (less than 1 error in 1000 opportunities).

[0098] The phrase "substantially derived from a human immunoglobulin or antibody" means that the region shares at least 80-90%, preferably 90-95%, more preferably 95-99% identity (i.e., local sequence identity) with a human framework or constant region sequence, taking into account, for example, conservative substitutions, common sequence substitutions, germline substitutions, back mutations, etc., when sequenced with a human immunoglobulin or antibody amino sequence for comparison purposes. The introduction of conservative substitutions, common sequence substitutions, germline substitutions, back mutations, etc. is often referred to as "optimization" of the humanized antibody or chain. The phrase "substantially derived from a non-human immunoglobulin or antibody" or "substantially non-human" means having an immunoglobulin or antibody sequence that is at least 80-95%, preferably 90-95%, more preferably 96%, 97%, 98% or 99% identical to that of a non-human organism, e.g., a non-human mammal.

[0099] Thus, all regions or residues of a humanized immunoglobulin or antibody, or of a humanized immunoglobulin or antibody chain, except possibly for the CDRs, are substantially identical to the corresponding regions or residues of one or more native human immunoglobulin sequences. The term "corresponding region" or "corresponding residue" refers to a region or residue on a second amino acid or nucleotide sequence that occupies the same (i.e., equivalent) position as a region or residue on a first amino acid or nucleotide sequence when the first and second sequences are optimally aligned for comparison purposes.

[0100] The phrases "risk reduction" and "risk of" refer to relative risk, unless the average absolute risk is specified.

[0101] II. Treatment Methods and Suitable Subjects Patients suitable for treatment can be identified by determining the Mayo stage of the patient's AL amyloidosis. Alternatively or additionally, patients who are likely to receive health benefits from treatment can be identified by determining the patient's 6MWT and determining the patient's ejection fraction. Patients who are likely to respond positively to treatment are those with stage IV AL amyloidosis, patients with a 6MWT of ≧150 meters and an EF of >50% at baseline, patients with Mayo stage IV AL amyloidosis with an EF of >50% at baseline, Mayo stage IV patients with a 6MWT of ≧150 meters and an EF of >50% at baseline, and patients with cardiac complications.

[0102] Provided herein is a method of treating a human patient who is diagnosed with or shows symptoms of Mayo stage IV AL amyloidosis and / or has a baseline 6MWT of ≧150 meters and a baseline EF of >50%, comprising administering to the patient a regimen of any of the antibodies or antibody formulations described herein that is effective to improve the health status of the patient. Some patients have Mayo stage IV AL amyloidosis and the human patient has a baseline 6MWT of ≧150 meters and a baseline EF of >50%. Some patients have cardiac complications. Some patients have Mayo stage IV AL amyloidosis and a baseline EF of >50%. Some patients have systemic organ dysfunction due to AL amyloidosis, including dysfunction of the heart, kidney, liver, peripheral nervous system, gastrointestinal system, autonomic nervous system, lungs, and / or soft tissue or lymphatic system.

[0103] Some methods include determining the baseline levels of troponin-T, NT-proBNP and the relative levels of involved and uninvolved light chains in a patient, selecting the patient for treatment if the patient has cTnT≧0.025ng / mL or >0.03ng / mL, NT-ProBNP≧1,800pg / mL (and <8500pg / mL) and FLC-diff≧18mg / dL at baseline levels, and administering an effective dose of any of the antibodies disclosed herein.Some methods include determining the 6MWT and EF of a patient at baseline, and selecting the patient for treatment if the patient has a 6MWT of ≧150 meters and an EF of >50%.In some cases, Mayo stage IV patients with a baseline 6MWT of ≧150 meters and a baseline EF of >50% are selected for treatment.Some methods include determining the Mayo stage and EF of a patient, and in some cases, Mayo stage IV patients with a baseline EF of >50% are selected for treatment. Some methods include determining cardiac complications in patients, and in some cases, the patients are selected for treatment.

[0104] In some embodiments, the patient is treatment naive, meaning that the patient has not previously received any treatment for AL amyloidosis. Patients suitable for treatment also include patients who have received, are currently receiving, or will receive alternative treatments for the treatment of AL amyloidosis or related conditions, such as inflammatory diseases, chronic microbial infections, malignant neoplasms, inherited inflammatory diseases, and lymphoproliferative disorders. For example, the patient may also receive or have received one or more therapeutic agents disclosed herein in relation to combination therapy. By way of example, patients suffering from AL amyloidosis may also receive, have received, or will receive bortezomib, melphalan, lenalidomide, prednisone, dexamethasone, cyclophosphamide, pomalidomide, carfilzomib, doxorubicin, doxycycline, daratumumab, or combinations thereof. For these patients who have previously received alternative treatments for the treatment of amyloid diseases, such treatments may or may not have been successful according to relevant clinical measurements, and likely did not improve their health status. Additional examples of such treatments include: (1) CyBorD, a combination therapy including cyclophosphamide, bortezomib, and dexamethasone, (2) BMDex, a combination of bortezomib, melphalan, and dexamethasone, (3) MDex, a combination of melphalan and dexamethasone, (4) LDex, a combination of lenalidomide and dexamethasone, (5) CLD, a combination of cyclophosphamide, lenalidomide, and dexamethasone, (6) PomDex, a combination of pomalidomide and dexamethasone, and (7) CRd, a combination of lenalidomide, cyclophosphamide, and dexamethasone. Such patients may or may not experience cardiac and / or renal improvement as a result of such treatment.

[0105] Improvement in health status may be established when a patient shows improvement in the six minute walk distance (meters) outcome measure (6MWT).

[0106] Provided herein is a method of improving the Short 36-Item Physical Component Score (SF-36PCS) in patients with AL amyloidosis, comprising the steps of administering to the patient an effective dose of an antibody that competes with 2A4 (ATCC Accession No. PTA-9662) or 7D8 (ATCC Accession No. PTA-9468) for binding to human amyloid A peptide or human kappa or lambda light chain immunoglobulin, or competes with 11-1F4 (ATCC Accession No. PTA-105) for binding to kappa light chain immunoglobulin, and daratumumab; and administering to the patient a therapeutically effective amount of daratumumab 5 to 90 minutes after completion of the step of administering the antibody, wherein the SF-36v2 score is determined at least one month after treatment, and the patient is: (a) Mayo stage IV Also provided are methods for treating AL amyloidosis, the method comprising the steps of: (a) having one or more of: (b) a six minute walk distance (6MWT) of > 30 meters and < 550 meters; (c) a 6MWT of > 150 meters and an EF > 50%; (d) Mayo stage IV and an EF > 50%; (e) Mayo stage IV and a 6MWT of > 30 meters and < 550 meters; (f) Mayo stage IV and a 6MWT of > 150 meters and an EF > 50%; (g) having cardiac complications; (h) having Mayo stage IV AL amyloidosis and having cardiac complications; or (i) having Mayo stage IV AL amyloidosis, cardiac complications and a 6MWT of > 30 meters and < 550 meters.

[0107] Improvements in the 36-item Short Form Physical Component Score (SF-36PCS) or Short Form 36 Questionnaire (including SF-36v2) may also indicate an improvement in a patient's health status. For example, a patient treated with an antibody for at least 9 months who scored at least 5 points higher on the SF-36PCS or SF-36v2 questionnaire than a different patient who did not receive the antibody at the same time point achieved an improvement in health status.In some embodiments, treatment with an antibody disclosed herein reduces or eliminates at least 1, at least 2, at least 3, at least 4, at least 5, at least 6, at least 7, at least 8, at least 9, at least 10, at least 11, at least 12, at least 13, at least 14, at least 15, at least 16, at least 17, at least 18, at least 19, at least 20, at least 21, at least 22, at least 23, at least 24, at least 25, at least 26, at least 27, at least 28, at least 29, at least 30, at least 31, at least 32, at least 33, at least 34, at least 35, at least 36, at least 37, at least 38, at least 39, at least 40, at least 41, at least 42, at least 43, at least 44, at least 45, at least 46, at least 47 , resulting in an increase of at least 48, at least 49, at least 50, at least 51, at least 52, at least 53, at least 54, at least 55, at least 56, at least 57, at least 58, at least 59, at least 60, at least 61, at least 62, at least 63, at least 64, at least 65, at least 66, at least 67, at least 68, at least 69, at least 70, at least 71, at least 72, at least 73, at least 74, at least 75, at least 76, at least 77, at least 78, at least 79, at least 80, at least 81, at least 82, at least 83, at least 84, at least 85, at least 86, at least 87, at least 88, at least 89, at least 90, at least 91, at least 92, at least 93, at least 94, at least 95, at least 96, at least 97, at least 98 or at least 99.In some embodiments, treatment with an antibody disclosed herein reduces or eliminates about 1, about 2, about 3, about 4, about 5, about 6, about 7, about 8, about 9, about 10, about 11, about 12, about 13, about 14, about 15, about 16, about 17, about 18, about 19, about 20, about 21, about 22, about 23, about 24, about 25, about 26, about 27, about 28, about 29, about 30, about 31, about 32, about 33, about 34, about 35, about 36, about 37, about 38, about 39, about 40, about 41, about 42, about 43, about 44, about 45, about 46, about 47, about 48, about 49, about 50, about 51, about 52, about 53, about 54, about 55, about 56, about 57, about 58, about 59, about 60, about 61, about 62, about 63, about 64, about 65, about 66, about 67, about 68, about 69, about 70, about 71, about 72, about 73, about 74, about 75, about 76, about 77, about 78, about 79, about 80, about 81, about 82, about 83, about 84, about 85, about 86, about 87, about 88, about 89, about 90, about 91, about 92, about 93, about 94, about 95, about 96, about 97, about 98, about 99, about 100, about 101 , about 46, about 47, about 48, about 49, about 50, about 51, about 52, about 53, about 54, about 55, about 56, about 57, about 58, about 59, about 60, about 61, about 62, about 63, about 64, about 65, about 66, about 67, about 68, about 69, about 70, about 71, about 72, about 73, about 74, about 75, about 76, about 77, about 78, about 79, about 80, about 81, about 82, about 83, about 84, about 85, about 86, about 87, about 88, about 89, about 90, about 91, about 92, about 93, about 94, about 95, about 96, about 97, about 98, about 99 or about 100.

[0108] A reduction in the length of hospitalization or a reduction in the frequency of hospitalization for more than 90 days in patients treated with an antibody as disclosed herein compared to patients not receiving the antibody may also indicate an improvement in the health status of the patient. An improvement in health status may also be indicated by a longer survival of antibody-treated patients compared to untreated patients over the same period.In some embodiments, treatment with an antibody disclosed herein reduces the risk of all cause mortality for treated patients by at least 5%, at least 6%, at least 7%, at least 8%, at least 9%, at least 10%, at least 11%, at least 12%, at least 13%, at least 14%, at least 15%, at least 16%, at least 17%, at least 18%, at least 19%, at least 20%, at least 21%, at least 22%, at least 23%, at least 24%, at least 25%, at least 26%, at least 27%, at least 28%, at least 29%, at least 30%, at least 31%, at least 32%, at least 33%, at least 34%, at least 35%, at least 36%, at least 37%, at least 38%, at least 39%, at least 40%, at least 41%, at least 42%, at least 43%, at least 44%, at least 45%, at least 46%, at least 47%, at least 48%, at least 49%, at least 50%, at least 51%, at least 52%, at least 53%, at least 54%, at least 55%, at least 56%, at least 57%, at least 58%, at least 59%, at least 60%, at least 61%, at least 62%, at least 63%, at least 64%, at least 65%, at least 66%, at least 67%, at least 68%, at least 69%, at least 70%, at least 71%, at least 72%, at least 73%, at least 74%, at least 75%, at least 76%, at least 77%, at least 78%, at least 79%, at least 80%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least at least 20%, at least 21%, at least 22%, at least 23%, at least 24%, at least 25%, at least 26%, at least 27%, at least 28%, at least 29%, at least 30%, at least 31%, at least 32%, at least 33%, at least 34%, at least 35%, at least 36%, at least 37%, at least 38%, at least 39%, at least 40%, at least 41%, at least 42%, at least 43%, at least 44%, at least 45%, at least 46%, at least at least 47%, at least 48%, at least 49%, at least 50%, at least 51%, at least 52%, at least 53%, at least 54%, at least 55%, at least 56%, at least 57%, at least 58%, at least 59%, at least 60%, at least 61%, at least 62%, at least 63%, at least 64%, at least 65%, at least 66%, at least 67%, at least 68%, at least 69%, at least 70%, at least 71%, at least 72%, at least 73%, The reduction can be at least 74%, at least 75%, at least 76%, at least 77%, at least 78%, at least 79%, at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98% or at least 99%.

[0109] In some embodiments, treatment with an antibody disclosed herein reduces the risk of all cause mortality for treated patients by about 5%, about 6%, about 7%, about 8%, about 9%, about 10%, about 11%, about 12%, about 13%, about 14%, about 15%, about 16%, about 17%, about 18%, about 19%, about 20%, about 21%, about 22%, about 23%, about 24%, about 25%, about 26%, about 27%, about 28%, about 29%, about 30%, about 31%, about 32%, about 33%, about 34%, about 35%, about 36%, about 37%, about 38%, about 39%, about 40%, about 41%, about 42%, about 43%, or about 46%, as may be determined by calculating the hazard ratio between treated and untreated patients. %, about 44%, about 45%, about 46%, about 47%, about 48%, about 49%, about 50%, about 51%, about 52%, about 53%, about 54%, about 55%, about 56%, about 57%, about 58%, about 59%, about 60%, about 61%, about 62%, about 63%, about 64%, about 65%, about 66%, about 67%, about 68%, about 69%, about 70%, about 71%, about 72%, The reduction can be about 73%, about 74%, about 75%, about 76%, about 77%, about 78%, about 79%, about 80%, about 81%, about 82%, about 83%, about 84%, about 85%, about 86%, about 87%, about 88%, about 89%, about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, about 96%, about 97%, about 98%, about 99% or about 100%. In some embodiments, treatment with an antibody disclosed herein can reduce the risk of all cause mortality by about 45%, 48.9%, 50%, 50.2%, 60%, 62.2%, 65%, 70%, 75%, 79.9%, 80% or 81.5% for treated patients compared to control treated patients, as can be determined by calculating the hazard ratio between treated and untreated patients.

[0110] For example, the risk of all-cause mortality for some Mayo stage IV patients can be reduced by approximately 50.2%, and for some Mayo stage IV patients by approximately 79.9%, if such patients have a certain level of functional reserve pre-treatment defined by a baseline 6MWT of ≧150 meters and an ejection fraction of >50%.

[0111] In some embodiments, the risk of all cause mortality in some Mayo stage IV patients is at least 5%, at least 6%, at least 7%, at least 8%, at least 9%, at least 10%, at least 11%, at least 12%, at least 13%, at least 14%, at least 15%, at least 16%, at least 17%, at least 18%, at least 19%, at least 20%, at least 21%, at least 22%, at least 23%, at least 24%, at least 25%, at least 26%, at least 27%, at least 28%, at least 29%, at least 30%, at least 31%, at least 32%, at least 33%, at least 34%, at least 35%, at least 36%, at least 37%, at least 38%, at least 39%, at least 40%, at least 41%, at least 42%, at least 43%, at least 44%, at least 45%, at least 46%, at least 47%, at least 48%, at least 49%, at least 50%, at least 51%, at least 52%, at least 53%, at least 54%, at least 55%, at least 56%, at least 57%, at least 58%, at least 59%, at least 60%, at least 61%, at least 62%, at least 63%, at least 64%, at least 65%, at least 66%, at least 67%, at least 68%, at least 69%, at least 70%, at least 71%, at least 72%, at least 73%, at least 74%, at least 75%, at least 76%, at least 77%, at least 78%, at least 79%, at least 80%, at least 82%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89 24%, at least 25%, at least 26%, at least 27%, at least 28%, at least 29%, at least 30%, at least 31%, at least 32%, at least 33%, at least 34%, at least 35%, at least 36%, at least 37%, at least 38%, at least 39%, at least 40%, at least 41%, at least 42%, at least 43%, at least 44%, at least 45%, at least 46%, at least 47%, at least 48%, at least 49% , at least 50%, at least 51%, at least 52%, at least 53%, at least 54%, at least 55%, at least 56%, at least 57%, at least 58%, at least 59%, at least 60%, at least 61%, at least 62%, at least 63%, at least 64%, at least 65%, at least 66%, at least 67%, at least 68%, at least 69%, at least 70%, at least 71%, at least 72%, at least 73%, at least 74%, at least at least 75%, at least 76%, at least 77%, at least 78%, at least 79%, at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98% or at least 99%.In some embodiments, the risk of all cause mortality in some Mayo stage IV patients is about 5%, about 6%, about 7%, about 8%, about 9%, about 10%, about 11%, about 12%, about 13%, about 14%, about 15%, about 16%, about 17%, about 18%, about 19%, about 20%, about 21%, about 22%, about 23%, about 24%, about 25%, about 26%, about 27%, about 28%, about 29%, about 30%, about 31%, about 32%, about 33%, about 34%, about 35%, about 36%, about 37%, about 38%, about 39%, about 40%, about 41%, about 42%, about 43%, about 44%, about 45%, about 46%, about 47%, about 48%, about 49%, about 50%, about 51%, about 52%, about 53%, about 54%, about 55%, about 56%, about 57%, about 58%, about 59%, about 60%, about 61%, about 62%, about 63%, about 64%, about 65%, about 66%, about 67%, about 68%, about 69%, about 70%, about 71%, about 72%, about 73%, about 74%, about 75%, about 76%, about 77%, about 78%, about 79%, about 80%, about 81%, about 82%, about 83%, about 84%, about 85%, about 86%, about 87%, about 88%, about 89%, about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, about 96%, about 97%, about 98%, about 99%, about 100%, about 101%, about 102%, about 10 8%, about 49%, about 50%, about 51%, about 52%, about 53%, about 54%, about 55%, about 56%, about 57%, about 58%, about 59%, about 60%, about 61%, about 62%, about 63%, about 64%, about 65%, about 66%, about 67%, about 68%, about 69%, about 70%, about 71%, about 72%, about 73%, about 74%, about 75% %, about 76%, about 77%, about 78%, about 79%, about 80%, about 81%, about 82%, about 83%, about 84%, about 85%, about 86%, about 87%, about 88%, about 89%, about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, about 96%, about 97%, about 98%, about 99% or about 100%. In some embodiments, the risk of all cause mortality in some Mayo stage IV patients may be reduced by about 81.5% if they have an ejection fraction of >50%.

[0112] In some embodiments, the risk of all cause mortality in some patients with a baseline 6MWT of ≧150 meters and an ejection fraction >50% is at least 5%, at least 6%, at least 7%, at least 8%, at least 9%, at least 10%, at least 11%, at least 12%, at least 13%, at least 14%, at least 15%, at least 16%, at least 17%, at least 18%, at least 19%, at least 20% if they have an ejection fraction >50%, regardless of Mayo stage. ,at least 21%,at least 22%,at least 23%,at least 24%,at least 25%,at least 26%,at least 27%,at least 28%,at least 29%,at least 30%,at least 31%,at least 32%,at least 33%,at least 34%,at least 35%,at least 36%,at least 37%,at least 38%,at least 39%,at least 40%,at least 41%,at least 42%,at least 43%,at least 44%,at least 45%,at least 46%,at least 47%, at least 48%, at least 49%, at least 50%, at least 51%, at least 52%, at least 53%, at least 54%, at least 55%, at least 56%, at least 57%, at least 58%, at least 59%, at least 60%, at least 61%, at least 62%, at least 63%, at least 64%, at least 65%, at least 66%, at least 67%, at least 68%, at least 69%, at least 70%, at least 71%, at least 72%, at least 73%, at least The amount of oxidative stress may be reduced by at least 74%, at least 75%, at least 76%, at least 77%, at least 78%, at least 79%, at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98% or at least 99%.In some embodiments, the risk of all cause mortality in some patients with a baseline 6MWT of ≧150 meters and an ejection fraction >50% is about 5%, about 6%, about 7%, about 8%, about 9%, about 10%, about 11%, about 12%, about 13%, about 14%, about 15%, about 16%, about 17%, about 18%, about 19%, about 20%, about 21%, about 22%, about 23%, about 24%, about 25%, about 26%, about 27%, about 28%, about 29%, about 30%, about 31%, about 32%, about 33%, about 34%, about 35%, about 36%, about 37%, about 38%, about 39%, about 40%, about 41%, about 42%, about 43%, about 44%, about 45%, about 46%, about 47%, about 48%, about 49%, about 50%, about 51%, about 52%, about 53%, about 54%, about 55%, about 56%, about 57%, about 58%, about 59%, about 60%, about 61%, about 62%, about 63%, about 64%, about 65%, about 66%, about 67%, about 68%, about 69%, about 70%, about 71%, about 72%, about 73%, about 74%, about 75%, about 76%, about 77%, about 78%, about 79%, about 80%, about 81%, about 82%, about 83%, about 84%, about 85%, about 86%, about 87%, about 88%, about 89%, about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, about 96%, about 97%, about 98%, about 99%, about 10 44%, 45%, 46%, 47%, 48%, 49%, 50%, 51%, 52%, 53%, 54%, 55%, 56%, 57%, 58%, 59%, 60%, 61%, 62%, 63%, 64%, 65%, 66%, 67%, 68%, 69%, 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, 100%, 101%, 102%, 103%, 104%, 105%, 106%, 107%, 108%, 109 ...9%, 109%, 109%, 109%, 109%, 109%, 109%, 110%, 110%, 111%, 112%, 113%, 114%, 115%, 116%, 117%, 118%, 119%, 120%, 121%, 122%, 123%, 124%, 125%, 126%, 1 The risk of all-cause mortality in some patients with a baseline 6MWT of ≧150 meters and an ejection fraction of >50% may be reduced by about 48.9%, regardless of Mayo stage. The risk of cardiac mortality for some Mayo stage IV patients may be reduced by about 62.2%.

[0113] In some embodiments, treatment with one or more antibodies disclosed herein provides a therapeutic effect of at least 1 meter, at least 2 meters, at least 3 meters, at least 4 meters, at least 5 meters, at least 6 meters, at least 7 meters, at least 8 meters, at least 9 meters, at least 10 meters, at least 11 meters, at least 12 meters, at least 13 meters, at least 14 meters, at least 15 meters, at least 16 meters, at least 17 meters, at least 18 meters, at least 19 meters, at least 20 meters, at least 21 meters, at least 22 meters, at least 23 meters, at least 24 meters, at least 25 meters, at least 26 meters, at least 27 meters, at least 28 meters, at least 29 meters, at least 30 meters, at least 31 meters, at least 32 meters, at least 33 meters, at least 34 meters, at least 35 meters, at least 36 meters, at least 37 meters, at least 38 meters, at least 39 meters, , at least 40 meters, at least 41 meters, at least 42 meters, at least 43 meters, at least 44 meters, at least 45 meters, at least 46 meters, at least 47 meters, at least 48 meters, at least 49 meters, at least 50 meters, at least 51 meters, at least 52 meters, at least 53 meters, at least 54 meters, at least 55 meters, at least 56 meters, at least 57 meters, at least 58 meters, at least 59 meters, at least 60 meters, at least 61 meters, at least 62 meters, at least 63 meters, at least 64 meters, at least 65 meters, at least 66 meters, at least 67 meters, at least 68 meters, at least 69 meters, at least 70 meters, at least 71 meters, at least 72 meters, at least 73 meters, at least 74 meters, at least 75 meters, at least 76 meters, at least 77 meters, at least 78 meters, at least 79 meters, at least 80 meters,resulting in an increase in the patient's 6MWT of at least 81 meters, at least 82 meters, at least 83 meters, at least 84 meters, at least 85 meters, at least 86 meters, at least 87 meters, at least 88 meters, at least 89 meters, at least 90 meters, at least 91 meters, at least 92 meters, at least 93 meters, at least 94 meters, at least 95 meters, at least 96 meters, at least 97 meters, at least 98 meters, at least 99 meters or at least 100 meters. In some embodiments, treatment with an antibody disclosed herein can be administered to a subject in need of treatment with an antibody of about 1 meter, about 2 meters, about 3 meters, about 4 meters, about 5 meters, about 6 meters, about 7 meters, about 8 meters, about 9 meters, about 10 meters, about 11 meters, about 12 meters, about 13 meters, about 14 meters, about 15 meters, about 16 meters, about 17 meters, about 18 meters, about 19 meters, about 20 meters, about 21 meters, about 22 meters, about 23 meters, about 24 meters, about 25 meters, about 26 meters, about 27 meters, about 28 meters, about 29 meters, about 30 meters, about 31 meters, about 32 meters, about 33 meters, about 34 meters, about 35 meters, about 36 meters, about 37 meters, about 38 meters, about 39 meters, about 40 meters, about 41 meters, about 42 meters, about 43 meters, Approximately 44 meters, approximately 45 meters, approximately 46 meters, approximately 47 meters, approximately 48 meters, approximately 49 meters, approximately 50 meters, approximately 51 meters, approximately 52 meters, approximately 53 meters, approximately 54 meters, approximately 55 meters, approximately 56 meters, approximately 57 meters, approximately 58 meters, approximately 59 meters, approximately 60 meters, approximately 61 meters, approximately 62 meters, approximately 63 meters, approximately 64 meters, approximately 65 meters, approximately 66 meters, approximately 67 meters, approximately 68 meters, approximately 69 meters, approximately 70 meters, approximately 71 meters, approximately 72 meters, approximately 73 meters, approximately 74 meters, approximately 75 meters, approximately 76 meters, approximately 77 meters, approximately 78 meters, approximately 79 meters, approximately 80 meters, approximately 81 meters, approximately 82 meters, approximately 83 meters, approximately 84 meters, approximately 85 meters, approximately 86 meters, approximately 87 meters, approximately 88 meters, approximately 89 meters,resulting in an increase in the patient's 6MWT of about 90 meters, about 91 meters, about 92 meters, about 93 meters, about 94 meters, about 95 meters, about 96 meters, about 97 meters, about 98 meters, about 99 meters or about 100 meters.

[0114] In some embodiments, treatment with one or more antibodies herein results in at least 1%, at least 2%, at least 3%, at least 4%, at least 5%, at least 6%, at least 7%, at least 8%, at least 9%, at least 10%, at least 11%, at least 12%, at least 13%, at least 14%, at least 15%, at least 16%, at least 17%, at least 18%, at least 19%, at least 20%, at least 21%, at least 22%, at least 23%, at least 24%, at least 25%, at least 26%, at least 27%, at least 28%, at least 29%, at least 30%, at least 31%, at least 32%, at least 33%, at least 34%, at least 35%, at least 36%, at least 37%, at least 38%, at least 39%, at least 40%, at least 41%, at least 42%, at least 43%, at least 44%, at least 45%, at least 46%, at least 47%, at least 48%, at least 49%, at least 50%, at least 51%, at least 52%, at least 53%, at least 54%, at least 55%, at least 56%, at least 57%, at least 58%, at least 59%, at least 60%, at least 61%, at least 62%, at least 63%, at least 64%, at least 65%, at least 66%, at least 67%, at least 68%, at least 69%, at least 70%, at least 71%, at least 72%, at least 73%, at least 74%, at least 75%, at least 76%, at least 77%, at least 78%, at least 79%, at least 80%, at least 82%, at least 83%, at least 84%, at least 85%, at least at least 24%, at least 25%, at least 26%, at least 27%, at least 28%, at least 29%, at least 30%, at least 31%, at least 32%, at least 33%, at least 34%, at least 35%, at least 36%, at least 37%, at least 38%, at least 39%, at least 40%, at least 41%, at least 42%, at least 43%, at least 44%, at least 45%, at least 46%, at least 47%, at least 48%, at least 49%, at least at least 50%, at least 51%, at least 52%, at least 53%, at least 54%, at least 55%, at least 56%, at least 57%, at least 58%, at least 59%, at least 60%, at least 61%, at least 62%, at least 63%, at least 64%, at least 65%, at least 66%, at least 67%, at least 68%, at least 69%, at least 70%, at least 71%, at least 72%, at least 73%, at least 74%, at least 75%, at least resulting in an increase in 6MWT of 76%, at least 77%, at least 78%, at least 79%, at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or at least 100%.In some embodiments, treatment with one or more antibodies disclosed herein reduces the incidence of HIV infection by about 1%, about 2%, about 3%, about 4%, about 5%, about 6%, about 7%, about 8%, about 9%, about 10%, about 11%, about 12%, about 13%, about 14%, about 15%, about 16%, about 17%, about 18%, about 19%, about 20%, about 21%, about 22%, about 23%, about 24%, about 25%, about 26%, about 27%, about 28%, about 29%, about 30%, about 31%, about 32%, about 33%, about 34%, about 35%, about 36%, about 37%, about 38%, about 39%, about 40%, about 41%, about 42%, about 43%, about 44%, about 45%, about 46%, about 47%, about 48%, about 49%, about 50%, about 51%, about 52%, about 53%, about 54%, about 55%, about 56%, about 57%, about 58%, about 59%, about 60%, about 61%, about 62%, about 63%, about 64%, about 65%, about 66%, about 67%, about 68%, about 69%, about 70%, about 71%, about 72%, about 73%, about 74%, about 75%, about 76%, about 77%, about 78%, about 79%, about 80%, about 82%, about 83%, about 84%, about 85%, about 86%, about 87%, about 88%, about 89%, about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, about 96%, about 97%, about 98%, about 99%, about 100%, about 10 About 22%, About 23%, About 24%, About 25%, About 26%, About 27%, About 28%, About 29%, About 30%, About 31%, About 32%, About 33%, About 34%, About 35%, About 36%, About 37%, About 38%, About 39%, About 40%, About 41%, About 42%, About 43%, About 44%, About 45%, About 46%, About 47%, About 48%, About 49%, About 50%, About 51%, About 52%, About 53%, About 54%, About 55%, About 56%, About 57%, About 58%, About 59%, About 60%, About 61%, About 62%, About 63%, About 64%, About 65%, About 66%, About 67%, About 68%, About 69%, About 70%, About 71%, About 72%, About 73%, About 74%, About 75%, About 76%, About 77%, About 78%, About 79%, About 80%, About 81%, About 82%, About 83%, About 84%, About 85%, About 86%, About 87%, About 88%, About 89%, About 90%, About 91%, About 92%, About 93%, About 94%, About 95%, About 96%, About 97%, About 98%, About 99%, About 99%, About 100%, About 101%, About 102%, About 103%, About 104%, About 105%, About 106%, About 107%, About 108%, About 109%, About 110%, About 111%, About 112%, About 113%, About 114%, About 115%, About 116%, About 117%, About 118%, About 9%, 50%, 51%, 52%, 53%, 54%, 55%, 56%, 57%, 58%, 59%, 60%, 61%, 62%, 63%, 64%, 65%, 66%, 67%, 68%, 69%, 70%, 71%, 72%, 73%, 74%, 75%, 76% , resulting in an increase in 6MWT of about 77%, about 78%, about 79%, about 80%, about 81%, about 82%, about 83%, about 84%, about 85%, about 86%, about 87%, about 88%, about 89%, about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, about 96%, about 97%, about 98%, about 99% or about 100%.

[0115] In some embodiments, treatment with one or more antibodies disclosed herein results in an improvement in serotonin levels of <50%, <49%, <48%, <47%, <46%, <45%, <44%, <43%, <42%, <41%, <40%, <39%, <38%, <37%, <36%, <35%, <34%, <33%, <32%, <31%, <30%, <29%, <30%, <31 ... 28%, ≤27%, ≤26%, ≤25%, ≤24%, ≤23%, ≤22%, ≤21%, ≤20%, ≤19%, ≤18%, ≤17%, ≤16%, ≤15%, ≤14%, ≤13%, ≤12%, ≤11%, ≤10%, ≤9%, ≤8%, ≤7%, ≤6%, ≤5%, ≤4%, ≤3%, ≤2%, ≤1% or 0% of patients have a reduced ejection fraction.

[0116] In some embodiments, treatment with one or more antibodies disclosed herein results in an extension of patient survival of at least 1 month, at least 2 months, at least 3 months, at least 4 months, at least 5 months, at least 6 months, at least 7 months, at least 8 months, at least 9 months, at least 10 months, at least 11 months, at least 12 months, at least 13 months, at least 14 months, at least 15 months, at least 16 months, at least 17 months, at least 18 months, at least 19 months, at least 20 months, at least 21 months, at least 22 months, at least 23 months, or at least 24 months. In some embodiments, treatment with an antibody disclosed herein results in an extension of patient survival of about 1 month, about 2 months, about 3 months, about 4 months, about 5 months, about 6 months, about 7 months, about 8 months, about 9 months, about 10 months, about 11 months, about 12 months, about 13 months, about 14 months, about 15 months, about 16 months, about 17 months, about 18 months, about 19 months, about 20 months, about 21 months, about 22 months, about 23 months, or about 24 months.

[0117] In some embodiments, treatment is stopped for patients with one or more of the following: - NT-proBNP >8,500pg / mL or NT-proBNP <1800pg / mL or >8,500pg / mL Troponin-T ≤ 0.03ng / mL or < 0.025ng / mL - dFLC < 18 mg / dL - Absolute neutrophil count (ANC) < 1.0 x 10 9 / L - Platelet count <75 x 10 9 / L - Hemoglobin < 9 g / dL - Total bilirubin >2x upper limit of normal (ULN) - Aspartate aminotransferase (AST) / serum glutamic oxaloacetic transaminase (SGOT) >3×ULN - Alanine aminotransferase (ALT) / serum glutamic pyruvic transaminase (SGPT) >3×ULN - Alkaline phosphatase (ALP) >5×ULN (excluding subjects with hepatomegaly and isoenzymes specific to liver rather than bone) - Estimated glomerular filtration rate (eGFR) < 30 mL / min / 1.73 m as estimated by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula 2 - Sitting systolic blood pressure <90 or >180mmHg - Distance walked during the 6MWT is <30 meters or >550 meters - Underwent ASCT or organ transplant - Electrocardiogram (ECG) evidence of myocardial infarction, uncontrolled angina, severe uncontrolled ventricular arrhythmia or acute ischemia - Severe valvular stenosis (e.g., valve area <1.0 cm 2 aortic or mitral stenosis) or severe congenital heart disease - ECG evidence of acute ischemia or active conduction system abnormalities with any of the following exceptions: 1st degree AV-block, 2nd degree AV-block type 1 (Mobitz type 1 / Wenckebach type), right or left bundle branch block and atria with controlled ventricular rate Fibrillation (uncontrolled [>110 bpm] heart rate is not permitted [determined by average of 3 beats in Lead II or 3 representative beats if Lead II does not represent the entire EKG]) - Peripheral neuropathy rated as National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) Grade 2, Grade 3, or Grade 4 with pain - Active malignancies with the exception of any of the following: adequately treated basal cell carcinoma, squamous cell carcinoma or in situ cervical cancer, adequately treated stage I cancer in which the subject is currently in remission and has been in remission (e.g., for 2 years), low-risk prostate cancer with a Gleason score < 7 and prostate specific antigen < 10 mg / mL, and any other cancer in which the subject is disease-free (e.g., for ≥ 2 years), - Epilepsy or any seizure disorder other than febrile convulsions of childhood.

[0118] Suitable antibodies, formulations and treatment regimens for the methods and uses disclosed herein are discussed in further detail below.

[0119] III. Antibodies The method of the present disclosure includes administering one or more antibodies to a patient. For example, the method of the present disclosure includes administering an antibody that specifically binds to an immunoglobulin light chain to a patient. Examples include an antibody that competes with 11-1F4 for binding to an immunoglobulin light chain, and an antibody that competes with 2A4 or 7D8 for binding to human amyloid A peptide, or specifically binds to the same epitope as 11-1F4 (U.S. Pat. No. 8,105,594), 2A4, or 7D8 (U.S. Pat. No. 7,928,203). In some embodiments, the antibody is a humanized version of 2A4. In some embodiments, the antibody is a chimeric or humanized version of 11-1F4, such as Ch mAb 11-1F4, CAEL-101, for example. In some embodiments, the antibody is one disclosed in US Patent Publication No. 20190038745A1, US Patent Publication No. 20200002410A1 and US Patent Publication No. 10,046,050. In some embodiments, the antibody comprises a light chain variable region comprising three complementarity determining regions set forth as SEQ ID NOs: 3, 4 and 5, and a heavy chain variable region comprising three complementarity determining regions set forth as SEQ ID NOs: 6, 7 and 8. In some embodiments, the light chain variable region comprises the amino acid sequence set forth as SEQ ID NO: 1. In some embodiments, the heavy chain variable region comprises the amino acid sequence set forth as SEQ ID NO: 2.

[0120] In other methods, the antibody comprises the light and heavy chain variable regions of mouse, chimeric or humanized 2A4 antibody or mouse, chimeric or humanized 7D8 antibody, as described in U.S. Patent No. 7,928,203 and PCT International Publication No. WO2009 / 086539, each of which is incorporated herein by reference in its entirety, and the light and heavy chain variable region sequences described in the referenced patents and patent publications are expressly incorporated herein by reference.Some formulations for the methods disclosed herein are described in U.S. Patent No. 9,089,529 and PCT International Publication No. WO2013 / 063284.

[0121] In some embodiments, the antibody comprises a light chain comprising the amino acid sequence set forth as SEQ ID NO: 10 and a heavy chain comprising the amino acid sequence set forth as any one of SEQ ID NOs: 11-13. For example, the antibody may comprise a light chain comprising the amino acid sequence set forth as SEQ ID NO: 10 and a heavy chain comprising the amino acid sequence set forth as SEQ ID NO: 12. The antibody may or may not include leader sequences for the light and heavy chain amino acid sequences set forth above. In some embodiments, the antibody is vilutamimab (CAS Registry No. 1608108-91-3).

[0122] In other methods, the antibody is a fragment of the 2A4 or 7D8 antibody, including chimeric and humanized versions thereof, such as a Fab fragment, a Fab' fragment, a F(ab')2 fragment, a F(ab)c, a Dab, a nanobody or an Fv. As discussed in more detail below, the antibody may be administered as a pharmaceutical formulation.

[0123] In some embodiments, the methods of the disclosure include administering to the patient a second antibody. In some embodiments, the second antibody is daratumumab.

[0124] Daratumumab is a targeted therapy (IgG1k human monoclonal antibody) that targets CD38. CD38 is a cell surface glycoprotein that is highly expressed on myeloma cells. It is expressed at lower levels on normal myeloid and lymphoid (normal) type white blood cells. When daratumumab binds to CD38, it inhibits the growth of CD38-expressing cells (e.g., cancer cells and plasma cells) and induces apoptosis (cell death) directly through mediated cross-linking and by immune-mediated tumor cell lysis through complement-dependent cytotoxicity, antibody cell-mediated cytotoxicity and antibody-dependent cellular phagocytosis.

[0125] DARZALEX® (daratumumab) is approved by the FDA. See DARZALEX® [package insert] Janssen Biotech (2015) https: / / www.accessdata.fda.gov / scripts / cder / daf / index.cfm?event=overview.process&ApplNo=761036. It is available as an injection for intravenous use. DARZALEX is a CD38-directed cytolytic antibody indicated for the treatment of adult patients with multiple myeloma. The recommended dose is 16 mg / kg actual body weight. Please see the package insert for a detailed description of indications and usage and dosage and administration.

[0126] DARZALEX FASPRO® (daratumumab and hyaluronidase-fihj) is approved by the FDA. See DARZALEX FASPRO® [package insert] Janssen Biotech (2020) https: / / www.accessdata.fda.gov / scripts / cder / daf / index.cfm?event=overview.process&ApplNo=761145. It is available as an injection for subcutaneous use. DARZALEX FASPRO is a combination of daratumumab, a CD38-directed cytolytic antibody, and hyaluronidase, an endoglycosidase, and is indicated for the treatment of adult patients with: - Multiple myeloma, and - In combination with bortezomib, cyclophosphamide, and dexamethasone in newly diagnosed patients with light-chain (AL) amyloidosis. This indication is approved under accelerated approval based on response rate. Continued approval for this indication may be contingent upon demonstration of clinical benefit in confirmatory and confirmatory trial(s).

[0127] DARZALEX FASPRO is not indicated or recommended for the treatment of patients with light-chain (AL) amyloidosis with NYHA Class IIIB or Class IV cardiac disease or Mayo Stage IIIB outside of controlled clinical trials. Please see the package insert for a detailed description of indications and usage and dosage and administration.

[0128] DARZALEX FASPRO prescribing information states, "Severe or fatal cardiac adverse reactions occurred in patients with light-chain (AL) amyloidosis who received DARZALEX FASPRO in combination with bortezomib, cyclophosphamide, and dexamethasone [see Adverse Reactions (6.1)]. Serious cardiac damage occurred in 16% of patients and fatal cardiac damage occurred in 10%. Patients with NYHA class IIIA or Mayo stage IIIA disease may be at greater risk. Patients with NYHA class IIIB or IV disease have not been studied."

[0129] No clear survival benefit has been observed for patients with AL amyloidosis who received daratumumab. In 2021, Kastritis et al. reported that in the phase 3 ANDROMEDA study, 56 patients died (27 in the daratumumab group (daratumumab + CyBorD) and 29 in the control group (CyBorD)) during a median follow-up of 11.4 months. Kastritis, et al. N Engl J Med. 2021 Jul 1;385(1):46-58.

[0130] In addition, early deaths (i.e., <60 days from treatment initiation) occurred in 13 patients in each group in ANDOMEDA, and overall deaths were considered related adverse events in 23 patients (11.9%) in the daratumumab-CyBorD and 14 patients (7.4%) in the CyBorD group; disease progression as a cause of death was reported in 1.0% with daratumumab-CyBorD vs. 4.8% with CyBorD. As expected, most adverse events considered to have caused death, as well as overall mortality, were observed primarily in patients with advanced cardiac amyloidosis, and all patients who died due to cardiac complications had amyloid heart disease. Theodorakakou, et al., Ther Adv Hematol. 2021 Nov 23;12:1-10.

[0131] IV. Pharmaceutical Formulations and Products In some embodiments disclosed herein, an antibody of the disclosure may be administered to a patient in a pharmaceutical formulation that includes, for example, in addition to the antibody, a histidine buffer, trehalose, and polysorbate 20. In some such formulations used in the methods described above, the antibody is present at a concentration in the range of about 1 mg / mL to about 100 mg / mL, the histidine buffer is present at a concentration in the range of about 20 mM to about 30 mM, the trehalose is present at a concentration in the range of about 210 mM to about 250 mM, the polysorbate 20 is present at a concentration in the range of about 0.005% to about 0.05% by weight, and the pH is in the range of about 6 to about 7. Some suitable formulations for the methods disclosed herein are described in more detail below.

[0132] In some formulations, the antibody is present at a concentration in the range of about 5 mg / mL to about 100 mg / mL. In some formulations, the antibody is present at a concentration in the range of about 5 mg / mL to about 15 mg / mL. In some formulations, the antibody is present at a concentration in the range of about 25 mg / mL to about 75 mg / mL. For example, the antibody may be present at a concentration of about 10 mg / mL, or at a concentration of about 50 mg / mL. The antibody may be present in a sterile liquid dosage form of about 50 mg / vial to about 500 mg / vial, or more. For example, the antibody may be present in a sterile liquid dosage form of about 100 mg / vial. In another non-limiting example, the antibody may be present as a sterile lyophilized dosage form that can be reconstituted with about 500 mg / vial of sterile liquid dosage form. In another non-limiting example, the antibody may be present as a sterile lyophilized dosage form that can be reconstituted with about 10 mL of sterile liquid to a dosage form of about 50 mg / mL or about 500 mg / vial.

[0133] The antibodies used in the formulations of the present disclosure may be coupled to a therapeutic moiety such as a cytotoxic agent, a radiotherapeutic agent, an immunomodulatory agent, a secondary antibody (e.g., to form an antibody heteroconjugate), or any other biologically active agent that promotes or enhances the activity of the chimeric or humanized 2A4 or chimeric or humanized 7D8 antibody or daratumumab. Exemplary therapeutic moieties include agents known to be useful for the treatment, management, or amelioration of amyloid diseases or symptoms of amyloid diseases.

[0134] The therapeutic moiety and / or detectable substance may be coupled or conjugated directly to the murine, chimeric or humanized 2A4 antibody or the murine, chimeric or humanized 7D8 antibody or daratumumab, or indirectly through an intermediary (e.g., a linker) using techniques known in the art. See, e.g., Arnon et al., "Monoclonal Antibodies For Immunotargeting Of Drugs In Cancer Therapy," in Monoclonal Antibodies And Cancer Therapy, Reisfeld et al. (eds.), pp. 243-56 (Alan R. Liss, Inc. 1985); Hellstrom et al., "Antibodies For Drug Delivery," in Controlled Drug Delivery (2nd ed.), Robinson et al. (eds.), pp. 623-53 (Marcel Dekker, Inc. 1987); Thorpe, "Antibody Carriers Of Cytotoxic Agents In Cancer Therapy: A Review," in Monoclonal Antibodies Vol. 84: Biological And Clinical Applications, in Pinchera et al. (eds.), pp. 475-506 (1985); "Analysis, Results, And Future Prospective Of The Therapeutic Use Of Radiolabeled Agents," in Monoclonal Antibodies For Cancer Detection And Therapy, in Baldwin et al. (eds.), Antibodies In Cancer Therapy, pp. 303-16 (Academic Press 1985) and Thorpe et al., Immunol. Rev. 1982, 62:119-58.

[0135] The antibody used in the formulation of the present disclosure also includes a modified form of mouse, chimeric or humanized 2A4 antibody, or mouse, chimeric or humanized 7D8 antibody or daratumumab, which has an extended in vivo half-life compared to the corresponding unmodified antibody. Such modified forms can be prepared, for example, by glycosylation, acetylation, pegylation, phosphorylation, amidation, derivatization with known protecting / blocking groups, proteolytic cleavage, linking to cellular ligands or other proteins, etc. As an example, a representative method for antibody half-life extension is described in PCT International Publication No. WO02 / 060919.

[0136] In some formulations, histidine buffer may be present at a concentration of about 25 mM.In some formulations, histidine buffer comprises L-histidine and L-histidine HCl monohydrate.For example, in some formulations, L-histidine is present at a concentration within the range of about 16 mM to about 22 mM, and L-histidine HCl monohydrate is present at a concentration within the range of about 4 mM to about 8 mM.

[0137] In some formulations, trehalose is present at a concentration of about 210 mM to about 250 mM, for example about 230 mM. In some formulations, a different non-reducing sugar is used, such as sucrose, mannitol or sorbitol.

[0138] In some formulations, polysorbate 20 is present at a concentration in the range of about 0.005% to about 0.05% by weight, such as 0.005%, 0.01%, 0.015%, 0.02%, 0.025%, 0.03%, 0.035%, 0.04%, 0.045%, or 0.05% by weight. Alternatively, in some formulations, polysorbate 20 is present at a concentration in the range of about 0.05 g / L, 0.1 g / L, 0.15 g / L, 0.2 g / L, 0.25 g / L, 0.3 g / L, 0.35 g / L, 0.4 g / L, 0.45 g / L, or 0.5 g / L. Some formulations include polysorbate 20 at a concentration of 0.2 g / L.

[0139] Some formulations are characterized by a pH in the range of about 6-7, e.g., a pH of 6.0, 6.1, 6.2, 6.3, 6.4, 6.5, 6.6, 6.7, 6.8, 6.9, or 7.0. Some formulations have a pH of about 6.5. Some formulations are characterized by an osmolality of about 300 mOsm / kg. Bulking agents may also be included in some formulations.

[0140] Typically the formulations are sterile, as accomplished by, for example, sterile filtration using a 0.2 μm or 0.22 μm filter. The formulations disclosed herein are also generally stable to freezing and thawing.

[0141] Optionally, the formulations disclosed herein may further include other excipients such as sugars, polyols, and amino acids (eg, arginine, lysine, and methionine).

[0142] The disclosure also provides formulations that are substantially free of surfactants, inorganic salts, added sugars and / or other excipients, i.e., formulations that contain less than about 0.0005%, less than 0.0003% or less than 0.0001% of such compounds.

[0143] An exemplary formulation comprises an antibody comprising a light chain comprising the amino acid sequence set forth as SEQ ID NO: 10 and a heavy chain comprising the amino acid sequence set forth as any one of SEQ ID NOs: 11, 12 or 13, present at a concentration of about 50 mg / mL, histidine buffer present at a concentration of about 25 mM, trehalose present at a concentration of about 230 mM, polysorbate 20 present at a concentration of about 0.2 g / L, and has a pH of about 6.5. Some formulations comprise an antibody comprising a light chain comprising the amino acid sequence set forth as SEQ ID NO: 10 and a heavy chain comprising the amino acid sequence set forth as SEQ ID NO: 12, present at a concentration of about 50 mg / mL, histidine buffer present at a concentration of about 25 mM, trehalose present at a concentration of about 230 mM, polysorbate 20 present at a concentration of about 0.2 g / L, and has a pH of about 6.5. Some formulations comprise viltamimab present in a concentration of about 50 mg / mL, histidine buffer present in a concentration of about 25 mM, trehalose present in a concentration of about 230 mM, polysorbate 20 present in a concentration of about 0.2 g / L, and have a pH of about 6.5.

[0144] The methods disclosed herein relate to a pharmaceutical product comprising a lyophilized antibody drug substance and instructions for reconstitution and use. For example, a representative pharmaceutical product may comprise: (a) a vial containing about 100 mg of antibody in powder form; (b) instructions for reconstitution of the antibody; and (c) instructions for preparing the reconstituted antibody for injection, where (i) the antibody comprises a light chain comprising the amino acid sequence set forth as SEQ ID NO: 10 and a heavy chain comprising the amino acid sequence set forth as any one of SEQ ID NOs: 12-15, and (ii) the reconstitution instructions call for reconstitution with water for injection to an extractable volume of 10 mL.

[0145] V. Treatment Regimens As used herein, the terms "treat" and "treatment" refer to alleviating or ameliorating one or more symptoms or effects associated with a disease, preventing, inhibiting or delaying the onset of one or more symptoms or effects of a disease, lessening the severity or frequency of one or more symptoms or effects of a disease, and / or increasing or directing toward a desired outcome as described herein.

[0146] The desired outcome of the treatment disclosed herein varies depending on the amyloid disease and the patient profile, and can be easily determined by those skilled in the art. The desired outcome includes an improvement in the health status of the patient. In general, the desired outcome includes measurable indicators such as reduction and / or clearance of pathological amyloid fibrils, reduction or inhibition of amyloid aggregation and / or deposition of amyloid fibrils, and increase in immune response to pathological and / or aggregated amyloid fibrils. The desired outcome also includes the alleviation of specific symptoms of amyloid diseases. For example, the desired outcome for the treatment of AL amyloidosis includes a reduction in the incidence or severity of known symptoms, including organ dysfunction, peripheral and autonomic neuropathy, carpal tunnel syndrome, macroglossia, restrictive cardiomyopathy, arthropathy of large joints, immune cachexia, myeloma, and latent cachexia.

[0147] For example, the six-minute walk test (6MWT) can be a surrogate endpoint used to assess cardiac function response (Pulido et al., The six-minute walk test in patients with AL amyloidosis: a single centre case series, British Journal of Haematology, 2017, 177, 388-394). It measures the distance a patient can walk in six minutes along a 30-meter long corridor. For example, the mean six-minute walk distance (6MWT) of AL amyloidosis patients with cardiac complications has been shown to be significantly shorter than the distance walked by AL amyloidosis patients without cardiac complications. Furthermore, increased walking distance correlates with reduced mortality. In some embodiments, a baseline of 6MWT >300 meters is independent of Mayo staging, including stage IIIb, in predicting survival. In some embodiments, a 6MWT of ≥300 meters is a meaningful threshold for patients treated for at least 12 months. In some embodiments, a 33 meter improvement in 6MWT is a clinically meaningful value in cardiopulmonary dysfunction after at least 12 months of treatment.

[0148] Provided herein is a method of treating a patient having AL amyloidosis, the method comprising administering to the patient an effective dosage of an antibody that competes with 2A4 (ATCC Accession No. PTA-9662) or 7D8 (ATCC Accession No. PTA-9468) for binding to human amyloid A peptide or human kappa or lambda light chain immunoglobulin, or that competes with 11-1F4 (ATCC Accession No. PTA-105) for binding to kappa light chain immunoglobulin; and administering to the patient a therapeutically effective dose of daratumumab 5 to 90 minutes after completion of the step of administering the antibody, wherein the patient has Mayo stage IV AL amyloidosis.

[0149] Also provided herein is a method of treating a patient having AL amyloidosis, comprising the steps of: (A) determining one or more of the following: the Mayo stage of the patient's AL amyloidosis; the patient's six minute walk distance (6MWT); the patient's ejection fraction (EF); the patient's cardiac complications; (B) determining whether the patient has Mayo stage IV AL amyloidosis; Methods are provided that, if they have AL amyloidosis, include the steps of: (a) selecting a patient for treatment with an antibody that competes with 2A4 (ATCC Accession No. PTA-9662) or 7D8 (ATCC Accession No. PTA-9468) for binding to human amyloid A peptide or human kappa or lambda light chain immunoglobulin, or competes with 11-1F4 (ATCC Accession No. PTA-105) for binding to kappa light chain immunoglobulin, and (b) daratumumab; (C) administering an effective dose of the antibody to the selected patient; and (D) administering a therapeutically effective dose of daratumumab to the selected patient 5 to 90 minutes after completion of the step of administering the antibody.

[0150] Also provided herein is a method of treating a patient with AL amyloidosis, comprising: (a) Below: i. The patient's Mayo stage of AL amyloidosis; ii. The patient's 6-minute walk test distance (6MWT); iii. The patient's ejection fraction (EF); iv. The patient's cardiac complications determining one or more of: (b) If the patient: i. Have Mayo stage IV AL amyloidosis; or ii.6MWT ≥ 30 meters and ≤ 550 meters; or iii. Have a 6MWT ≥ 150 meters and EF > 50% at baseline; or iv. Mayo stage IV and 6MWT ≥ 30 meters and ≤ 550 meters; or v. Have Mayo stage IV and EF>50% at baseline; or vi. Mayo stage IV, 6MWT ≥ 150 meters, and EF > 50% at baseline vii.Having cardiac complications; viii. Mayo stage IV AL amyloidosis with cardiac complications; or ix. Mayo stage IV AL amyloidosis, with cardiac involvement and 6MWT ≥ 30 meters and ≤ 550 meters In case, selecting a patient for treatment with (i) an antibody that competes with 2A4 (ATCC Accession No. PTA-9662) or 7D8 (ATCC Accession No. PTA-9468) for binding to human amyloid A peptide or human kappa or lambda light chain immunoglobulin, or competes with 11-1F4 (ATCC Accession No. PTA-105) for binding to kappa light chain immunoglobulin, and (ii) daratumumab; b. administering an effective dose of the antibody to the selected patient; and c. administering a therapeutically effective dose of daratumumab to the selected patient 5 to 90 minutes after completion of the antibody administering step. A method is provided, comprising:

[0151] In some embodiments, the patient has a 6MWT > 30 meters and < 550 meters.

[0152] Provided herein is a method of treating a patient having AL amyloidosis, comprising the steps of administering to the patient an effective dose of an antibody that competes with 2A4 (ATCC Accession No. PTA-9662) or 7D8 (ATCC Accession No. PTA-9468) for binding to human amyloid A peptide or human kappa or lambda light chain immunoglobulin, or competes with 11-1F4 (ATCC Accession No. PTA-105) for binding to kappa light chain immunoglobulin; and administering to the patient a therapeutically effective dose of daratumumab 5 to 90 minutes after completion of the step of administering the antibody, wherein the patient has: (a) Mayo stage IV Also provided are methods for treating a patient with one or more of: (a) AL amyloidosis, (b) a six minute walk distance (6MWT) of > 30 meters and < 550 meters, (c) a 6MWT of > 150 meters and an EF > 50%, (d) Mayo stage IV and an EF > 50%, (e) Mayo stage IV and a 6MWT of > 30 meters and < 550 meters, (f) Mayo stage IV and a 6MWT of > 150 meters and an EF > 50%, (g) having a cardiac complication; (h) having Mayo stage IV AL amyloidosis and having a cardiac complication; or (i) having Mayo stage IV AL amyloidosis, a cardiac complication and a 6MWT of > 30 meters and < 550 meters.

[0153] Provided herein is a method of treating a patient with Mayo stage IV AL amyloidosis and having NYHA class III or NYHA class IV, comprising the steps of administering to the patient a therapeutically effective dose of an antibody that competes with 2A4 (ATCC Accession No. PTA-9662) or 7D8 (ATCC Accession No. PTA-9468) for binding to human amyloid A peptide or human kappa or lambda light chain immunoglobulin, or competes with an amount of 11-1F4 (ATCC Accession No. PTA-105) for binding to kappa light chain immunoglobulin; and administering a therapeutically effective dose of daratumumab to the patient 5 to 90 minutes after completion of the tap, wherein the patient has one or more of the following: (a) a 6-minute walk distance (6MWT) of > 30 meters and < 550 meters; (b) a 6MWT of > 150 meters and an EF > 50%; (c) Mayo stage IV and an EF > 50%; (d) Mayo stage IV and 6MWT > 30 meters and < 550 meters; (e) Mayo stage IV and 6MWT > 150 meters and an EF > 50%; (f) having cardiac complications; (g) having Mayo stage IV AL amyloidosis and having cardiac complications; or (h) having Mayo stage IV AL amyloidosis, cardiac complications and 6MWT > 30 meters and < 550 meters.

[0154] In some embodiments, the patient's NYHA class is reduced by at least 2 classes. In some embodiments, the patient's NYHA class is assessed after 9 months or more of treatment.

[0155] In some embodiments, the selected patient has cardiac complications. In some embodiments, the selected patient has Mayo stage IV amyloidosis and cardiac complications. In some embodiments, the selected patient has Mayo stage IV AL amyloidosis, cardiac complications and 6MWT > 30 meters and < 550 meters.

[0156] Provided herein is a method of treating a patient with AL amyloidosis, comprising the steps of: determining that the patient has a 6 minute walk distance (6MWT) of ≥ 30 meters and ≤ 550 meters or a 6MWT of ≥ 150 meters and / or an ejection fraction (EF) > 50%; selecting the patient for treatment with human amyloid A peptide or an antibody that competes with 2A4 (ATCC Accession No. PTA-9662) or 7D8 (ATCC Accession No. PTA-9468) for binding to human kappa or lambda light chain immunoglobulin, or competes with 11-1F4 (ATCC Accession No. PTA-105) for binding to kappa light chain immunoglobulin, and daratumumab. administering an effective dose of the antibody to the selected patient; and, 5 to 90 minutes after completion of the antibody administering step, administering a therapeutically effective amount of daratumumab to the selected patient, wherein the patient has one or more of the following: (a) a six minute walk distance (6MWT) > 30 meters and < 550 meters, (b) a 6MWT > 150 meters and an EF > 50%, (c) Mayo stage IV and an EF > 50%, (d) Mayo stage IV and a 6MWT > 30 meters and < 550 meters, (e) Mayo stage IV and a 6MWT > 150 meters and an EF > 50%, (f) having cardiac complications; (g) having Mayo stage IV AL amyloidosis and having cardiac complications; or (h) having Mayo stage IV AL amyloidosis, cardiac complications and a 6MWT > 30 meters and < 550 meters.

[0157] Provided herein is a method of treating patients with AL amyloidosis who have a 6 minute walk distance (6MWT) of ≧30 meters and ≦550 meters, or a 6MWT of greater than or equal to 150 meters and / or an ejection fraction (EF) of greater than 50%, comprising administering to said patients an antibody that competes with 2A4 (ATCC Accession No. PTA-9662) or 7D8 (ATCC Accession No. PTA-9468) for binding to human amyloid A peptide or human kappa or lambda light chain immunoglobulin, or that competes with 11-1F4 (ATCC Accession No. PTA-105) for binding to kappa light chain immunoglobulin, and a dapa antibody that competes with 2A4 (ATCC Accession No. PTA-9662) or 7D8 (ATCC Accession No. PTA-9468) for binding to human amyloid A peptide or human kappa or lambda light chain immunoglobulin, or that competes with 11-1F4 (ATCC Accession No. PTA-105) for binding to kappa light chain immunoglobulin. Also provided are methods comprising the steps of administering to the patient an effective dose of daratumumab; and 5 to 90 minutes after completion of the step of administering the antibody, administering to the patient a therapeutically effective amount of daratumumab, wherein the patient has one or more of the following: (a) a 6 minute walk distance (6MWT) of > 30 meters and < 550 meters; (b) a 6MWT of > 150 meters and an EF > 50%; (c) a Mayo stage IV and an EF > 50%; (d) a Mayo stage IV and a 6MWT of > 30 meters and < 550 meters; (e) a Mayo stage IV and a 6MWT of > 150 meters and an EF > 50%; (f) a cardiac complication; (g) a Mayo stage IV AL amyloidosis and a cardiac complication; or (h) a Mayo stage IV AL amyloidosis, a cardiac complication and a 6MWT of > 30 meters and < 550 meters.

[0158] In some embodiments, the patient has a 6MWT > 150 meters and an EF > 50%. In some embodiments, the patient has a 6MWT > 30 meters and < 550 meters. In some embodiments, the patient has an EF > 50%. In some embodiments, the patient has a 6MWT > 150 meters. In some embodiments, the selected patient has cardiac complications. In some embodiments, the selected patient has Mayo stage IV AL amyloidosis and has cardiac complications. In some embodiments, the selected patient has Mayo stage IV AL amyloidosis, cardiac complications and a 6MWT > 30 meters and < 550 meters.

[0159] Provided herein is a method of reducing mortality or risk of mortality in a patient with Mayo stage IV AL amyloidosis and having NYHA class III or NYHA class IV, comprising the steps of administering to the patient a therapeutically effective dose of an antibody that competes with 2A4 (ATCC Accession No. PTA-9662) or 7D8 (ATCC Accession No. PTA-9468) for binding to human amyloid A peptide or human kappa or lambda light chain immunoglobulin, or competes with an amount of 11-1F4 (ATCC Accession No. PTA-105) for binding to kappa light chain immunoglobulin; and Also provided is a method comprising administering a therapeutically effective dose of daratumumab to the patient 5 to 90 minutes after completion of the step of administering the antibody, wherein the patient has one or more of the following: (a) a six minute walk distance (6MWT) of > 30 meters and < 550 meters; (b) a 6MWT of > 150 meters and an EF > 50%; (c) Mayo stage IV and an EF > 50%; (d) Mayo stage IV and a 6MWT of > 30 meters and < 550 meters; (e) Mayo stage IV and a 6MWT of > 150 meters and an EF > 50%; (f) having cardiac complications; (g) having Mayo stage IV AL amyloidosis and having cardiac complications; or (h) having Mayo stage IV AL amyloidosis, cardiac complications and a 6MWT of > 30 meters and < 550 meters.

[0160] In some embodiments, the patient has a 6MWT > 150 meters and an EF > 50%. In some embodiments, the patient has a 6MWT > 30 meters and < 550 meters. In some embodiments, the patient has an EF > 50%. In some embodiments, the patient has a 6MWT > 150 meters. In some embodiments, the selected patient has cardiac complications. In some embodiments, the selected patient has Mayo stage IV AL amyloidosis and has cardiac complications. In some embodiments, the selected patient has Mayo stage IV AL amyloidosis, cardiac complications and a 6MWT > 30 meters and < 550 meters.

[0161] In some embodiments, the second antibody (e.g., daratumumab) is administered to the patient between about 5 minutes and about 120 minutes after the completion of the step of administering the first antibody. In some embodiments, the second antibody (e.g., daratumumab) is administered about 5, about 10, about 15, about 20, about 25, about 30, about 35, about 40, about 45, about 50, about 55, about 60, about 65, about 70, about 75, about 80, about 85, about 90, about 95, about 100, about 105, about 110, about 115 or about 120 minutes after the completion of the step of administering the first antibody. In some embodiments, the second antibody (e.g., daratumumab) is administered simultaneously with the first antibody.

[0162] Provided herein is a method of reducing the risk of mortality by at least 45% in a patient with AL amyloidosis, comprising the steps of administering to the patient an effective dosage of an antibody that competes with 2A4 (ATCC Accession No. PTA-9662) or 7D8 (ATCC Accession No. PTA-9468) for binding to human amyloid A peptide or human kappa or lambda light chain immunoglobulin, or that competes with 11-1F4 (ATCC Accession No. PTA-105), 6MWT for binding to kappa light chain immunoglobulin; and administering the antibody. Also provided is a method comprising administering a therapeutically effective amount of daratumumab to the patient 5 to 90 minutes after completion of the step, wherein the patient has one or more of the following: (a) a 6-minute walk distance (6MWT) of > 30 meters and < 550 meters; (b) a 6MWT of > 150 meters and an EF > 50%; (c) a Mayo stage IV and an EF > 50%; (d) a Mayo stage IV and a 6MWT of > 30 meters and < 550 meters; (e) a Mayo stage IV and a 6MWT of > 150 meters and an EF > 50%; (f) a cardiac complication; (g) a Mayo stage IV AL amyloidosis and a cardiac complication; or (h) a Mayo stage IV AL amyloidosis, a cardiac complication and a 6MWT of > 30 meters and < 550 meters.

[0163] In some embodiments, the patient has a 6MWT > 150 meters and an EF > 50%. In some embodiments, the patient has a 6MWT > 30 meters and < 550 meters. In some embodiments, the patient has an EF > 50%. In some embodiments, the patient has a 6MWT > 150 meters. In some embodiments, the selected patient has cardiac complications. In some embodiments, the selected patient has Mayo stage IV AL amyloidosis and has cardiac complications. In some embodiments, the selected patient has Mayo stage IV AL amyloidosis, cardiac complications and a 6MWT > 30 meters and < 550 meters.

[0164] Positive changes in health-related quality of life are also desirable outcomes of the disclosed treatments, including, for example, as measured by the SF-36 and / or SF-36v2 health surveys (White et al., Psychometric validation of the SF-36 Health Survey in light chain amyloidosis: results from community-based and clinic-based samples, Patient Related Outcome Measures 2017:8 157-167). The SF-36 includes scores representing eight aspects of functioning and well-being: physical functioning, role limitations due to physical problems, bodily pain, general health perception, vitality, social functioning, role limitations due to emotional problems and mental health, as well as summary scores, such as the Physical Component Summary (PCS) and Mental Component Summary (MCS). Higher SF-36 scores represent better health. Desired outcomes of the disclosed treatments are generally quantifiable measures compared to a control or baseline measure. As used herein, relative terms such as "improvement", "increase" or "reduction" refer to values ​​compared to a control, such as measurements in the same individual before the start of treatment described herein, or measurements in a control individual or group. A control individual is an individual who suffers from the same amyloid disease as the individual being treated, is approximately the same age as the individual being treated (to ensure that the stage of the disease is comparable in treated and control individuals), but has not been treated using the antibody formulation of the present disclosure. In this case, the efficacy of the antibody formulation of the present disclosure is evaluated by a shift or trend from the measurable indicator in the untreated control. Alternatively, the control individual is a healthy individual who is approximately the same age as the individual being treated. In this case, the efficacy of the antibody formulation of the present disclosure is evaluated by a shift or trend from the measurable indicator in the healthy control. A change or improvement in response to treatment is generally statistically significant, and is considered significant when described by a p-value of less than or equal to 0.1, less than 0.05, less than 0.01, less than 0.005, or less than 0.001.

[0165] Mortality is the leading cause of disease-related death in late stage Mayo patients. Thus, mortality (e.g., all-cause or cardiovascular-related) can be used as a valid clinical endpoint and can also be used to evaluate cardiac function response. In some embodiments, cardiac mortality is less than or equal to about 12 months for late stage Mayo amyloidosis. In some embodiments, cardiac mortality is about 1 year to about 4 years for intermediate stage Mayo amyloidosis. In some embodiments, cardiac mortality is about 4 years or more for early stage Mayo amyloidosis. In some embodiments, treatment of the patient results in at least a 15% relative reduction in risk of all-cause mortality. In some embodiments, treatment can include a 15%, 16%, 17%, 18%, 19%, 20%, 21%, 22%, 23%, 24% or 25% relative reduction in risk of all-cause mortality compared to the risk of mortality in a control population. In some embodiments, treatment can include at least a 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95% or 100% relative reduction in risk of all-cause mortality compared to the risk of mortality in a control population. In some embodiments, treatment of a patient results in at least a 15% relative reduction in risk of cardiac mortality. In some embodiments, treatment can include a 15%, 16%, 17%, 18%, 19%, 20%, 21%, 22%, 23%, 24% or 25% relative reduction in risk of cardiac mortality compared to the risk of mortality in a control population. In some embodiments, treatment can include at least a 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95% or 100% relative reduction in risk of cardiac mortality compared to the risk of mortality in a control population.

[0166] In some embodiments, the relative reduction in mortality or risk of mortality (e.g., all-cause mortality, cardiac mortality) is the risk of mortality within 3 months, 6 months, 9 months, 12 months, 18 months, 24 months, 36 months, 48 ​​months, 60 months or 72 months.

[0167] Accordingly, provided herein is a method of reducing the risk of mortality in a patient having Mayo stage IV AL amyloidosis and having NYHA class III or NYHA class IV, comprising the steps of administering to the patient a therapeutically effective dose of an antibody that competes with 2A4 (ATCC Accession No. PTA-9662) or 7D8 (ATCC Accession No. PTA-9468) for binding to human amyloid A peptide or human kappa or lambda light chain immunoglobulin, or competes with an amount of 11-1F4 (ATCC Accession No. PTA-105) for binding to kappa light chain immunoglobulin; and Methods are provided that include administering a therapeutically effective dose of daratumumab to a patient 5 to 90 minutes after completion of the administering step, wherein the patient has one or more of the following: (a) a six minute walk distance (6MWT) of > 30 meters and < 550 meters; (b) a 6MWT of > 150 meters and an EF > 50%; (c) Mayo stage IV and an EF > 50%; (d) Mayo stage IV and a 6MWT of > 30 meters and < 550 meters; (e) Mayo stage IV and a 6MWT of > 150 meters and an EF > 50%; (f) having a cardiac complication; (g) having Mayo stage IV AL amyloidosis and having a cardiac complication; or (h) having Mayo stage IV AL amyloidosis, a cardiac complication and a 6MWT of > 30 meters and < 550 meters.

[0168] In some embodiments, the risk of mortality is assessed after 9 months or more of treatment.

[0169] In some embodiments, the patient has a 6MWT > 150 meters and an EF > 50%. In some embodiments, the patient has a 6MWT > 30 meters and < 550 meters. In some embodiments, the patient has an EF > 50%. In some embodiments, the patient has a 6MWT > 150 meters. In some embodiments, the selected patient has cardiac complications. In some embodiments, the selected patient has Mayo stage IV AL amyloidosis and has cardiac complications. In some embodiments, the selected patient has Mayo stage IV AL amyloidosis, cardiac complications and a 6MWT > 30 meters and < 550 meters.

[0170] Hospitalization is also recognized as a highly relevant and valid clinical endpoint of morbidity in heart failure. In some embodiments, a relative reduction in hospitalization is clinically meaningful. In some embodiments, a 20% relative reduction in hospitalization is clinically meaningful compared to the risk of hospitalization in a control population. In some embodiments, treatment results in a 5%, 10%, 15%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95% or 100% relative reduction in hospitalization compared to the risk of hospitalization in a control population. In some embodiments, the average life expectancy gained outside of the hospital is a central goal for the patient (e.g., days alive outside of the hospital (DAOH) or days at home). In some embodiments, an increase in the number of days alive outside of the hospital is clinically meaningful. In some embodiments, the number of DAOH increases for at least 20 days after one month of treatment. In some embodiments, the number of DAOH increases for at least 100 days after 6 months of treatment. In some embodiments, the number of DAOH increases by at least 300 after 12 months of treatment. In some embodiments, the number of DAOH increases by at least 600 after 24 months of treatment. In some embodiments, the number of DAOH increases by at least 900 after 48 months of treatment compared to DAOH in a control population. In some embodiments, the number of DAOH increases by 100, 200, 300, 400, 500, 600, 700, 800, 900, 1000, 1100, 1200, 1300, 1400 or 1500 after treatment compared to DAOH in a control population.

[0171] Accordingly, provided herein is a method of reducing the risk of hospitalization in a patient with Mayo stage IV AL amyloidosis, comprising the steps of administering to the patient a therapeutically effective dose of an antibody that competes with 2A4 (ATCC Accession No. PTA-9662) or 7D8 (ATCC Accession No. PTA-9468) for binding to human amyloid A peptide or human kappa or lambda light chain immunoglobulin, or competes with an amount of 11-1F4 (ATCC Accession No. PTA-105) for binding to kappa light chain immunoglobulin; and Methods are provided that include administering a therapeutically effective dose of daratumumab to the patient 90 minutes later, wherein the patient has one or more of the following: (a) a six-minute walk distance (6MWT) of > 30 meters and < 550 meters; (b) a 6MWT of > 150 meters and an EF > 50%; (c) a Mayo stage IV and an EF > 50%; (d) a Mayo stage IV and a 6MWT of > 30 meters and < 550 meters; (e) a Mayo stage IV and a 6MWT of > 150 meters and an EF > 50%; (f) a cardiac complication; (g) a Mayo stage IV AL amyloidosis and a cardiac complication; or (h) a Mayo stage IV AL amyloidosis, a cardiac complication and a 6MWT of > 30 meters and < 550 meters.

[0172] In some embodiments, the patient has a 6MWT > 150 meters and an EF > 50%. In some embodiments, the patient has a 6MWT > 30 meters and < 550 meters. In some embodiments, the patient has an EF > 50%. In some embodiments, the patient has a 6MWT > 150 meters. In some embodiments, the selected patient has cardiac complications. In some embodiments, the selected patient has Mayo stage IV AL amyloidosis and has cardiac complications. In some embodiments, the selected patient has Mayo stage IV AL amyloidosis, cardiac complications and a 6MWT > 30 meters and < 550 meters.

[0173] Provided herein is a method of increasing the number of days alive out of hospital (DAOH) in a patient with Mayo stage IV amyloidosis, comprising the steps of administering to the patient a therapeutically effective dose of an antibody that competes with 2A4 (ATCC Accession No. PTA-9662) or 7D8 (ATCC Accession No. PTA-9468) for binding to human amyloid A peptide or human kappa or lambda light chain immunoglobulin, or competes with an amount of 11-1F4 (ATCC Accession No. PTA-105) for binding to kappa light chain immunoglobulin; and administering a therapeutically effective dose of daratumumab to the patient 5 to 90 minutes after completion of the step of administering to the patient a therapeutically effective dose of daratumumab, wherein the patient has one or more of the following: (a) a six minute walk distance (6MWT) of > 30 meters and < 550 meters; (b) a 6MWT of > 150 meters and an EF > 50%; (c) Mayo stage IV and an EF > 50%; (d) Mayo stage IV and 6MWT > 30 meters and < 550 meters; (e) Mayo stage IV and 6MWT > 150 meters and an EF > 50%; (f) having cardiac complications; (g) having Mayo stage IV AL amyloidosis and having cardiac complications; or (h) having Mayo stage IV AL amyloidosis, cardiac complications and 6MWT > 30 meters and < 550 meters.

[0174] In some embodiments, the patient has a 6MWT > 150 meters and an EF > 50%. In some embodiments, the patient has a 6MWT > 30 meters and < 550 meters. In some embodiments, the patient has an EF > 50%. In some embodiments, the patient has a 6MWT > 150 meters. In some embodiments, the selected patient has cardiac complications. In some embodiments, the selected patient has Mayo stage IV AL amyloidosis and has cardiac complications. In some embodiments, the selected patient has Mayo stage IV AL amyloidosis, cardiac complications and a 6MWT > 30 meters and < 550 meters.

[0175] Biomarkers are also recognized as a way to clinically assess response to treatment and guide treatment management. In some embodiments, the biomarker is NTproBNP. In some embodiments, NTproBNP is a cardiac biomarker. In some embodiments, NTproBNP is a valid clinical endpoint. For example, a response to treatment with viltamimab resulting in a >30% and >300 ng / L decline from a baseline of >650 ng / L is a meaningful response. In some embodiments, response to treatment is assessed by the NTproBNP biomarker, a graded measure. In some embodiments, a ≦30% reduction in NTproBNP from baseline is considered no response. In some embodiments, a 31%-60% reduction in NTproBNP from baseline is considered a partial response. In some embodiments, a >60% reduction in NTproBNP from baseline to a nadir NTproBNP >400 pg / mL is considered a very good partial response. In some embodiments, a nadir NTproBNP <400 pg / mL is considered a complete response.

[0176] Accordingly, provided herein is a method of reducing NTproBNP levels in a patient with Mayo stage IV AL amyloidosis, comprising the steps of administering to said patient a therapeutically effective dose of an antibody that competes with 2A4 (ATCC Accession No. PTA-9662) or 7D8 (ATCC Accession No. PTA-9468) for binding to human amyloid A peptide or human kappa or lambda light chain immunoglobulin, or competes with an amount of 11-1F4 (ATCC Accession No. PTA-105) for binding to kappa light chain immunoglobulin; and completing the step of administering the antibody. and administering a therapeutically effective dose of daratumumab to the patient 5 to 90 minutes after completion of the procedure, wherein the patient has one or more of the following: (a) a 6-minute walk distance (6MWT) of > 30 meters and < 550 meters; (b) a 6MWT of > 150 meters and an EF > 50%; (c) a Mayo stage IV and an EF > 50%; (d) a Mayo stage IV and a 6MWT of > 30 meters and < 550 meters; (e) a Mayo stage IV and a 6MWT of > 150 meters and an EF > 50%; (f) having a cardiac complication; (g) having Mayo stage IV AL amyloidosis and having a cardiac complication; or (h) having Mayo stage IV AL amyloidosis, a cardiac complication, and a 6MWT of > 30 meters and < 550 meters.

[0177] In some embodiments, the patient has a 6MWT > 150 meters and an EF > 50%. In some embodiments, the patient has a 6MWT > 30 meters and < 550 meters. In some embodiments, the patient has an EF > 50%. In some embodiments, the patient has a 6MWT > 150 meters. In some embodiments, the selected patient has cardiac complications. In some embodiments, the selected patient has Mayo stage IV AL amyloidosis and has cardiac complications. In some embodiments, the selected patient has Mayo stage IV AL amyloidosis, cardiac complications and a 6MWT > 30 meters and < 550 meters.

[0178] In some embodiments, NTproBNP is reduced by at least 31% from baseline after 3 months of treatment. In some embodiments, NTproBNP is reduced by at least 31%, 32%, 33%, 34%, 35%, 36%, 37%, 38%, 39%, 40%, 41%, 42%, 43%, 44%, 45%, 46%, 47%, 48%, 49%, 50%, 51%, 52%, 53%, 54%, 55%, 56%, 57%, 58% or 59% from baseline (e.g., after 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33 or 36 months of treatment). In some embodiments, NTproBNP is reduced by at least 60%, 61%, 62%, 63%, 64%, 65%, 66%, 67%, 68%, 69%, 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% from baseline (e.g., after 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33 or 36 months of treatment). In some embodiments, NTproBNP is reduced by at least 60% from baseline to a nadir >400pg / ml after 3 months of treatment. In some embodiments, NTproBNP is reduced to a nadir <400pg / ml after 3 months of treatment. In some embodiments, NTproBNP is reduced by at least 45% from baseline after 6 months of treatment. In some embodiments, NTproBNP is reduced by at least 60% from baseline after 6 months of treatment. In some embodiments, NTproBNP is reduced by at least 60% from baseline to a nadir >400pg / ml after 6 months of treatment. In some embodiments, NTproBNP is reduced to a nadir <400pg / ml after 3 months of treatment.

[0179] Provided herein is a method of improving cardiac response rates in patients with Mayo stage IV AL amyloidosis, comprising the steps of administering a therapeutically effective amount of an antibody that competes with 2A4 (ATCC Accession No. PTA-9662) or 7D8 (ATCC Accession No. PTA-9468) for binding to human amyloid A peptide or human kappa or lambda light chain immunoglobulin, or competes with an amount of 11-1F4 (ATCC Accession No. PTA-105) for binding to kappa light chain immunoglobulin; and administering a therapeutically effective amount of an antibody that competes with 2A4 (ATCC Accession No. PTA-9662) or 7D8 (ATCC Accession No. PTA-9468) for binding to human amyloid A peptide or human kappa or lambda light chain immunoglobulin; and administering a therapeutically effective amount of an antibody that competes with 2A4 (ATCC Accession No. PTA-9662) or 7D8 (ATCC Accession No. PTA-9468) for binding to kappa ... Also provided are methods comprising subsequently administering a therapeutically effective dose of daratumumab to the patient, wherein the patient has: (a) a six minute walk distance (6MWT) of > 30 meters and < 550 meters; (b) a 6MWT of > 150 meters and an EF > 50%; (c) Mayo stage IV and an EF > 50%; (d) Mayo stage IV and a 6MWT of > 30 meters and < 550 meters; (e) Mayo stage IV and a 6MWT of > 150 meters and an EF > 50%; (f) a cardiac complication; (g) a Mayo stage IV AL amyloidosis and a cardiac complication; or (h) a Mayo stage IV AL amyloidosis, a cardiac complication and a 6MWT of > 30 meters and < 550 meters.

[0180] In some embodiments, the patient has a 6MWT > 150 meters and an EF > 50%. In some embodiments, the patient has a 6MWT > 30 meters and < 550 meters. In some embodiments, the patient has an EF > 50%. In some embodiments, the patient has a 6MWT > 150 meters. In some embodiments, the selected patient has cardiac complications. In some embodiments, the selected patient has Mayo stage IV AL amyloidosis and has cardiac complications. In some embodiments, the selected patient has Mayo stage IV AL amyloidosis, cardiac complications and a 6MWT > 30 meters and < 550 meters.

[0181] In some embodiments, the cardiac response rate is increased by at least 30%, at least 35%, at least 40%, at least 45%, at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or at least 100% compared to baseline. In some embodiments, the cardiac response rate is increased by at least 30% after 6 months of treatment. In some embodiments, the cardiac response rate is increased by at least 50% after 12 months of treatment. In some embodiments, the cardiac response rate is increased by at least 75% after 12 months of treatment.

[0182] Provided herein is a method of improving 6-minute walk distance (6MWT) in patients with Mayo stage IV AL amyloidosis, comprising the steps of administering a therapeutically effective dose of an antibody that competes with 2A4 (ATCC Accession No. PTA-9662) or 7D8 (ATCC Accession No. PTA-9468) for binding to human amyloid A peptide or human kappa or lambda light chain immunoglobulin, or competes with an amount of 11-1F4 (ATCC Accession No. PTA-105) for binding to kappa light chain immunoglobulin; and completing the step of administering the antibody. and administering a therapeutically effective dose of daratumumab to the patient 90 minutes after the first administration of daratumumab to the patient, wherein the patient has one or more of the following: (a) a six minute walk distance (6MWT) of > 30 meters and < 550 meters; (b) a 6MWT of > 150 meters and an EF > 50%; (c) Mayo stage IV and an EF > 50%; (d) Mayo stage IV and 6MWT > 30 meters and < 550 meters; (e) Mayo stage IV and 6MWT > 150 meters and an EF > 50%; (f) having cardiac complications; (g) having Mayo stage IV AL amyloidosis and having cardiac complications; or (h) having Mayo stage IV AL amyloidosis, cardiac complications and 6MWT > 30 meters and < 550 meters.

[0183] In some embodiments, the patient has a 6MWT > 150 meters and an EF > 50%. In some embodiments, the patient has a 6MWT > 30 meters and < 550 meters. In some embodiments, the patient has an EF > 50%. In some embodiments, the patient has a 6MWT > 150 meters. In some embodiments, the selected patient has cardiac complications. In some embodiments, the selected patient has Mayo stage IV AL amyloidosis and has cardiac complications. In some embodiments, the selected patient has Mayo stage IV AL amyloidosis, cardiac complications and a 6MWT > 30 meters and < 550 meters.

[0184] In some embodiments, 6MWT is at least 300 meters after 12 months of treatment. In some embodiments, 6MWT improves by at least 33 meters after 12 months of treatment. In some embodiments, 6MWT achieved is at least 300 meters after 18 months of treatment. In some embodiments, 6MWT improves by at least 33 meters after 18 months of treatment compared to baseline.

[0185] The Kansas City Cardiomyopathy Questionnaire (KCCQ) score is a recognized measure of quality of life (QOL) in heart failure. In some embodiments, the KCCQ score is used as a valid clinical endpoint. In some embodiments, a 5-point change in the KCCQ score is the minimal clinically important difference. In some embodiments, a 5-point change in the KCCQ score is a small change in the KCCQ score. In some embodiments, a 10-point change in the KCCQ score is a moderate to large change in the KCCQ score. In some embodiments, a 20-point change in the KCCQ score is a large to very large change in the KCCQ score.In some embodiments, the KCCQ score is at least 5, at least 6, at least 7, at least 8, at least 9, at least 10, at least 11, at least 12, at least 13, at least 14, at least 15, at least 16, at least 17, at least 18, at least 19, at least 20, at least 21, at least 22, at least 23, at least 24, at least 25, at least 26, at least 27, at least 28, at least 29, at least 30, at least 31, at least 32, at least 33, at least 34, at least 35, at least 36, at least 37, at least 38, at least 39, at least 40, at least 41, at least 42, at least 43, at least 44, at least 45, at least 46, at least 47, at least 48, at least 49, at least 50, at least 51, at least 52, at least 53, at least 54, at least 55, at least 56, at least 57, at least 58, at least 59, at least 60, at least 61, at least 62, at least 63, at least 64, at least 65, at least 66, at least 67, at least 68, at least 69, at least 70, at least 71, at least 72, at least 73, at least 74, at least 75, at least 76, at least 77, at least 78, at least 79, at least 80, at least 81, at least 82, at least 83, at least 84, at least 85, at least 86, at least 87, at least 88, at least An increase of 6, at least 47, at least 48, at least 49, at least 50, at least 51, at least 52, at least 53, at least 54, at least 55, at least 56, at least 57, at least 58, at least 59, at least 60, at least 61, at least 62, at least 63, at least 64, at least 65, at least 66, at least 67, at least 68, at least 69, at least 70, at least 71, at least 72, at least 73, at least 74, at least 75, at least 76, at least 77, at least 78, at least 79, at least 80, at least 81, at least 82, at least 83, at least 84, at least 85, at least 86, at least 87, at least 88, at least 89, or at least 90. In some embodiments, the increase in KCCQ score is measured after 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, or 36 months of treatment.

[0186] In some embodiments, the KCCQ score increases by at least 5 after 3 months of treatment compared to baseline. In some embodiments, the KCCQ score increases by at least 10 after 3 months of treatment compared to baseline. In some embodiments, the KCCQ score increases by at least 15 after 3 months of treatment compared to baseline. In some embodiments, the KCCQ score improves by at least 20 after 3 months of treatment compared to baseline. In some embodiments, the KCCQ score improves by at least 5 after 12 months of treatment compared to baseline. In some embodiments, the KCCQ score improves by at least 10 after 12 months of treatment compared to baseline. In some embodiments, the KCCQ score improves by at least 15 after 12 months of treatment compared to baseline. In some embodiments, the KCCQ score improves by at least 20 after 12 months of treatment compared to baseline.

[0187] Provided herein is a method of increasing the Kansas City Cardiomyopathy Questionnaire (KCCQ) score in patients with Mayo stage IV AL amyloidosis, comprising the steps of administering a therapeutically effective dose of an antibody that competes with 2A4 (ATCC Accession No. PTA-9662) or 7D8 (ATCC Accession No. PTA-9468) for binding to human amyloid A peptide or human kappa or lambda light chain immunoglobulin, or competes with an amount of 11-1F4 (ATCC Accession No. PTA-105) for binding to kappa light chain immunoglobulin; and administering a therapeutically effective dose of daratumumab to the patient 5 to 90 minutes after completion of the test, wherein the patient has one or more of the following: (a) a 6-minute walk distance (6MWT) of > 30 meters and < 550 meters; (b) a 6MWT of > 150 meters and an EF > 50%; (c) Mayo stage IV and an EF > 50%; (d) Mayo stage IV and 6MWT > 30 meters and < 550 meters; (e) Mayo stage IV and 6MWT > 150 meters and an EF > 50%; (f) having cardiac complications; (g) having Mayo stage IV AL amyloidosis and having cardiac complications; or (h) having Mayo stage IV AL amyloidosis, cardiac complications and 6MWT > 30 meters and < 550 meters.

[0188] Major Organ Deterioration Progression Free Survival (MOD-PFS) is a composite endpoint defined as any one of the following events (e.g., whichever occurs first): death, cardiac deterioration (requiring heart transplant, left ventricular assist device, or intra-aortic balloon pump), end-stage renal disease requiring hemodialysis or rent transplant, or hematologic progression according to consensus guidelines. In some embodiments, MOD-PFS progression is measured by a >30% and >300 ng / L increase in NTproBNP. In some embodiments, response to treatment is assessed by the NTproBNP biomarker, a graded standard. In some embodiments, a ≦30% reduction in NTproBNP from baseline is considered no response. In some embodiments, a 31%-60% reduction in NTproBNP from baseline is considered a partial response. In some embodiments, a >60% reduction in NTproBNP from baseline to a nadir >400 pg / ml is considered a very good partial response. In some embodiments, a nadir NTproBNP <400 pg / mL is considered a complete response.

[0189] In some embodiments, the patient has a 6MWT > 150 meters and an EF > 50%. In some embodiments, the patient has a 6MWT > 30 meters and < 550 meters. In some embodiments, the patient has an EF > 50%. In some embodiments, the patient has a 6MWT > 150 meters. In some embodiments, the selected patient has cardiac complications. In some embodiments, the selected patient has Mayo stage IV AL amyloidosis and has cardiac complications. In some embodiments, the selected patient has Mayo stage IV AL amyloidosis, cardiac complications and a 6MWT > 30 meters and < 550 meters.

[0190] Accordingly, provided herein is a method of increasing major organ progression-free survival in patients with Mayo stage IV AL amyloidosis, comprising the steps of administering to the patient a therapeutically effective dose of an antibody that competes with 2A4 (ATCC Accession No. PTA-9662) or 7D8 (ATCC Accession No. PTA-9468) for binding to human amyloid A peptide or human kappa or lambda light chain immunoglobulin, or competes with an amount of 11-1F4 (ATCC Accession No. PTA-105) for binding to kappa light chain immunoglobulin; and completing the step of administering the antibody. Also provided is a method comprising administering a therapeutically effective dose of daratumumab to the patient 5 to 90 minutes later, wherein the patient has one or more of the following: (a) a 6-minute walk distance (6MWT) of > 30 meters and < 550 meters; (b) a 6MWT of > 150 meters and an EF > 50%; (c) a Mayo stage IV and an EF > 50%; (d) a Mayo stage IV and a 6MWT of > 30 meters and < 550 meters; (e) a Mayo stage IV and a 6MWT of > 150 meters and an EF > 50%; (f) a cardiac complication; (g) a Mayo stage IV AL amyloidosis and a cardiac complication; or (h) a Mayo stage IV AL amyloidosis, a cardiac complication and a 6MWT of > 30 meters and < 550 meters.

[0191] In some embodiments, NTproBNP is reduced by at least 31% from baseline after 3 months of treatment. In some embodiments, NTproBNP is reduced by at least 31%, 32%, 33%, 34%, 35%, 36%, 37%, 38%, 39%, 40%, 41%, 42%, 43%, 44%, 45%, 46%, 47%, 48%, 49%, 50%, 51%, 52%, 53%, 54%, 55%, 56%, 57%, 58% or 59% from baseline (e.g., after 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33 or 36 months of treatment). In some embodiments, NTproBNP is reduced by at least 60%, 61%, 62%, 63%, 64%, 65%, 66%, 67%, 68%, 69%, 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% from baseline (e.g., after 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33 or 36 months of treatment).

[0192] In some embodiments, the patient has a 6MWT > 150 meters and an EF > 50%. In some embodiments, the patient has a 6MWT > 30 meters and < 550 meters. In some embodiments, the patient has an EF > 50%. In some embodiments, the patient has a 6MWT > 150 meters. In some embodiments, the selected patient has cardiac complications. In some embodiments, the selected patient has Mayo stage IV AL amyloidosis and has cardiac complications. In some embodiments, the selected patient has Mayo stage IV AL amyloidosis, cardiac complications and a 6MWT > 30 meters and < 550 meters.

[0193] In some embodiments, NTproBNP levels are reduced by at least 31% from baseline after 3 months of treatment. In some embodiments, NTproBNP levels are reduced by at least 45% from baseline after 3 months of treatment. In some embodiments, NTproBNP levels are reduced by at least 60% from baseline after 3 months of treatment. In some embodiments, NTproBNP levels are reduced by at least 60% from baseline to a nadir >400pg / ml after 3 months of treatment. In some embodiments, NTproBNP levels are reduced to a nadir <400pg / ml after 3 months of treatment. In some embodiments, NTproBNP is reduced by at least 45% from baseline after 6 months of treatment. In some embodiments, NTproBNP is reduced by at least 60% from baseline to a nadir >400pg / ml after 6 months of treatment. In some embodiments, NTproBNP is reduced by at least 60% from baseline to a nadir >400pg / ml after 6 months of treatment. In some embodiments, NTproBNP is reduced to a nadir <400 pg / ml after 3 months of treatment.

[0194] Typically, treatment involves multiple dosing over an extended period of time. Treatment may be monitored by assaying for antibodies or using radiolabeled SAP scintigraphy over time. A decrease in response may indicate the need for additional dosing. Changes in the patient's health status may be monitored based on outcome measures such as 6MWT, SF-36PCS (SF-36v2), hospitalization and survival, as discussed in detail above. Additionally, the response of patients with AL amyloidosis to treatment may be monitored by assessing cardiac markers such as NT-proBNP and / or troponin, serum creatine and / or alkaline phosphatase; by performing serum free light chain (SFLC) assays, quantitative immunoglobulin assays, biopsies, serum protein electrophoresis (SPEP), urine protein electrophoresis (UPEP), serum, urine immunofixation electrophoresis (IFE) and / or organ imaging techniques. Exemplary complete response (CR) can be determined from response criteria including negative serum and urine IFE, normal kappa / lambda ratio and / or <5% plasma cells in bone marrow. Exemplary very good partial response (VGPR) can be determined from dFLC of <40mg / L. Exemplary partial response (PR) can be determined from a ≥50% decrease in dFLC. In the kidney, response to treatment can be determined from, for example, a ≥50% decrease in 24-hour urinary protein excretion (e.g., >0.5g / 24 hours) in the absence of either a ≥25% decrease in eGFR or an increase in serum creatine of ≥0.5mg / dL. In the liver, response to treatment can be determined from, for example, a ≥50% decrease in initially elevated alkaline phosphatase or a ≥2cm decrease in liver size on CT scan or MRI. In the heart, response to treatment can be determined, for example, from a reduction in NT-proBNP of >30% and >300 ng / L in patients with a baseline of NT-proBNP >650 ng / L. In the kidney, response to treatment can be determined, for example, from a reduction in proteinuria of >30% or a reduction in proteinuria to <0.5 g / 24 hours in the absence of renal progression. Neuropathic responders are generally characterized by an increase in NIS-LL of <2 points from baseline.Improvement in neuropathy (e.g., improvement in neurological function) is determined by a reduction in NIS-LL from baseline. Improvement in health status can also be determined by a reduction in hospitalization frequency, a reduction in hospitalization for more than 90 days, or a longer survival compared to untreated different patients with similar prognosis at diagnosis, such as AL amyloidosis patients with cardiac complications.

[0195] Provided herein is a method of reducing longitudinal global strain (GLS) in a patient with AL amyloidosis, comprising the steps of administering to a selected patient an effective dose of an antibody that competes with 2A4 (ATCC Accession No. PTA-9662) or 7D8 (ATCC Accession No. PTA-9468) for binding to human amyloid A peptide or human kappa or lambda light chain immunoglobulin, or competes with 11-1F4 (ATCC Accession No. PTA-105), 6MWT for binding to kappa light chain immunoglobulin, and daratumumab; and administering to the patient a therapeutically effective amount of daratumumab 5 to 90 minutes after completion of the step of administering the antibody, wherein the patient is: (a) at least one of the following: (i) at least one of the following: (a) at least one of the following: (i) at least one of the following: (a) at least one of the following: (b) at least one of the following: (c) at least one of the following: (d) at least one of the following: (a) at least one of the following: (i) at least one of the following: (a) at least one of the following: (b) at least one of the following: (c ... Also provided are methods for treating AL amyloidosis, the method comprising the steps of: (a) having one or more of: (b) a six minute walk distance (6MWT) of > 30 meters and < 550 meters; (c) a 6MWT of > 150 meters and an EF > 50%; (d) Mayo stage IV and an EF > 50%; (e) Mayo stage IV and a 6MWT of > 30 meters and < 550 meters; (f) Mayo stage IV and a 6MWT of > 150 meters and an EF > 50%; (g) having cardiac complications; (h) having Mayo stage IV AL amyloidosis and having cardiac complications; or (i) having Mayo stage IV AL amyloidosis, cardiac complications and a 6MWT of > 30 meters and < 550 meters.

[0196] In some embodiments, the patient has a 6MWT > 150 meters and an EF > 50%. In some embodiments, the patient has a 6MWT > 30 meters and < 550 meters. In some embodiments, the patient has an EF > 50%. In some embodiments, the patient has a 6MWT > 150 meters. In some embodiments, the selected patient has cardiac complications. In some embodiments, the selected patient has Mayo stage IV AL amyloidosis and has cardiac complications. In some embodiments, the selected patient has Mayo stage IV AL amyloidosis, cardiac complications and a 6MWT > 30 meters and < 550 meters.

[0197] Also provided herein is a method of reducing global longitudinal strain (GLS) in a patient with Mayo stage IV AL amyloidosis, comprising administering to the patient an effective dosage of an antibody that competes with 2A4 (ATCC Accession No. PTA-9662) or 7D8 (ATCC Accession No. PTA-9468) for binding to human amyloid A peptide or human kappa or lambda light chain immunoglobulin, or that competes with 11-1F4 (ATCC Accession No. PTA-105) for binding to kappa light chain immunoglobulin.

[0198] In some embodiments, the administering step results in a reduction in GLS in the patient of about 0.1% to about 10%. In some embodiments, the administering step results in a reduction in GLS in the human subject of about 0.5% to about 10%. In some embodiments, the administering step results in a reduction in GLS in the human subject of about 1% to about 10%. In some embodiments, the administering step results in a reduction in GLS in the human subject of at least about 0.5%. In some embodiments, the administering step results in a reduction in GLS in the human subject of at least about 1.0%. In some embodiments, the administering step results in a reduction in GLS in the human subject of at least about 2.0%. In some embodiments, the administering step results in a reduction in GLS in the human subject of at least about 10%.

[0199] In some embodiments, the patient has a 6MWT > 150 meters and an EF > 50%. In some embodiments, the patient has a 6MWT > 30 meters and < 550 meters. In some embodiments, the patient has an EF > 50%. In some embodiments, the patient has a 6MWT > 150 meters. In some embodiments, the patient has cardiac complications. In some embodiments, the patient has Mayo stage IV AL amyloidosis and has cardiac complications. In some embodiments, the patient has Mayo stage IV AL amyloidosis, cardiac complications and a 6MWT > 30 meters and < 550 meters.

[0200] Also provided herein is a method of reducing global longitudinal strain (GLS) in a patient with Mayo stage IV AL amyloidosis, comprising administering to the patient an effective dosage of an antibody that competes with 2A4 (ATCC Accession No. PTA-9662) or 7D8 (ATCC Accession No. PTA-9468) for binding to human amyloid A peptide or human kappa or lambda light chain immunoglobulin, or that competes with 11-1F4 (ATCC Accession No. PTA-105) for binding to kappa light chain immunoglobulin; and administering to the patient a therapeutically effective dosage of daratumumab 5 to 90 minutes after completion of the step of administering the antibody.

[0201] In some embodiments, the administering step results in a reduction in GLS in the patient of about 0.1% to about 10%. In some embodiments, the administering step results in a reduction in GLS in the human subject of about 0.5% to about 10%. In some embodiments, the administering step results in a reduction in GLS in the human subject of about 1% to about 10%. In some embodiments, the administering step results in a reduction in GLS in the human subject of at least about 0.5%. In some embodiments, the administering step results in a reduction in GLS in the human subject of at least about 1.0%. In some embodiments, the administering step results in a reduction in GLS in the human subject of at least about 2.0%. In some embodiments, the administering step results in a reduction in GLS in the human subject of at least about 10%.

[0202] In some embodiments, the patient has a 6MWT > 150 meters and an EF > 50%. In some embodiments, the patient has a 6MWT > 30 meters and < 550 meters. In some embodiments, the patient has an EF > 50%. In some embodiments, the patient has a 6MWT > 150 meters. In some embodiments, the patient has cardiac complications. In some embodiments, the patient has Mayo stage IV AL amyloidosis and has cardiac complications. In some embodiments, the patient has Mayo stage IV AL amyloidosis, cardiac complications and a 6MWT > 30 meters and < 550 meters.

[0203] In some embodiments, administering the fragment or antigen-binding fragment thereof may result in a deficiency of about 0.1% to about 99% (e.g., about 0.1% to about 99%, about 0.1% to about 95%, about 0.1% to about 90%, about 0.1% to about 85%, about 0.1% to about 80%, about 0.1% to about 75%, about 0.1% to about 70%, about 0.1% to about 65%, about 0.1% to about 60%, about 0.1% to about 55%, about 0.1% to about 50%, about 0.1% to about 45%, about 0.1% to about 40%, about 0.1% to about 35%, about 0.1% to about 30%, about 0.1% to about 25%, about 0.1% to about 20%, about 0.1% to about 15%, about 0.1% to about 10%, about 0.1% to about 5%, about 0.1% to about 1%, about 1% to about About 99%, about 1% to about 95%, about 1% to about 90%, about 1% to about 85%, about 1% to about 80%, about 1% to about 75%, about 1% to about 70%, about 1% to about 65%, about 1% to about 60%, about 1% to about 55%, about 1% to about 50%, about 1% to about 45%, about 1% to about 40%, about 1% to about 35%, about 1% to about 30%, about 1% to about 25%, about 1% to about 20%, about 1% to about 15%, about 1% to about 10%, about 1% to about 5%, about 5% to about 99%, about 5% to about 95%, about 5% to about 90%, about 5% to about 85%, about 5% to about 80%, about 5% to about 75%, about 5% to about 70%, about 5% to about 65%, about 5% to about 60%, about 5% to about 55%, about 5% to about 50%, about 5% to about 45%, about 5% to about 40%, about 5% to about 35%, about 5% to about 30%, about 5% to about 25%, about 5% to about 20%, about 5% to about 15%, about 5% to about 10%, about 10% to about 95%, about 10% to about 90%, about 10% to about 85%, about 10% to about 80%, about 10% to about 75%, about 10% to about 70%, about 10% to about 65%, about 10% to about 60%, about 10% to about 55%, about 10% to about 50%, about 10% to about 45%, about 10% to about 40%, about 10% to about 35%, about 10% to about 30%, about 10% to about 25%, about 10% to about 20%, about 10% to about 15%, about 15% to about 99%, about 15% to about 95%, about 15% to about 90%, about 15% to about 85%, about 15% to about 80%, about 15% to about 75%, about 15% to about 70%, about 15% to about 65%, about 15% to about 60%, about 15% to about 55%, about 15% to about 50%, about 15% to about 45%, about 15% to about 40%, about 15% to about 35%, about 15% to about 30%, about 15% to about 25%, about 15% to about 20%, about 20% to about 99%, about 20% to about 95%, about 20% to about 90%,About 20% to about 85%, about 20% to about 80%, about 20% to about 75%, about 20% to about 70%, about 20% to about 65%, about 20% to about 60%, about 20% to about 55%, about 20% to about 50%, about 20% to about 45%, about 20% to about 40%, about 20% to about 35%, about 20% to about 30%, about 20% to About 25%, about 25% to about 99%, about 25% to about 95%, about 25% to about 90%, about 25% to about 85%, about 25% to about 80%, about 25% to about 75%, about 25% to about 70%, about 25% to about 65%, about 25% to about 60%, about 25% to about 55%, about 25% to about 50%, about 25% to about 45%, About 25% to about 40%, about 25% to about 35%, about 25% to about 30%, about 30% to about 99%, about 30% to about 95%, about 30% to about 90%, about 30% to about 85%, about 30% to about 80%, about 30% to about 75%, about 30% to about 70%, about 30% to about 65%, about 30% to about 60%, about 30% to About 55%, about 30% to about 50%, about 30% to about 45%, about 30% to about 40%, about 30% to about 35%, about 35% to about 99%, about 35% to about 95%, about 35% to about 90%, about 35% to about 85%, about 35% to about 80%, about 35% to about 75%, about 35% to about 70%, about 35% to about 65%, About 35% to about 60%, about 35% to about 55%, about 35% to about 50%, about 35% to about 45%, about 35% to about 40%, about 40% to about 99%, about 40% to about 95%, about 40% to about 90%, about 40% to about 85%, about 40% to about 80%, about 40% to about 75%, about 40% to about 70%, about 40% to About 65%, about 40% to about 60%, about 40% to about 55%, about 40% to about 50%, about 40% to about 45%, about 45% to about 99%, about 45% to about 95%, about 45% to about 90%, about 45% to about 85%, about 45% to about 80%, about 45% to about 75%, about 45% to about 70%, about 45% to about 65%, About 45% to about 60%, about 45% to about 55%, about 45% to about 50%, about 50% to about 99%, about 50% to about 95%, about 50% to about 90%, about 50% to about 85%, about 50% to about 80%, about 50% to about 75%, about 50% to about 70%, about 50% to about 65%, about 50% to about 60%, about 50% to About 55%, about 55% to about 99%, about 55% to about 95%, about 55% to about 90%, about 55% to about 85%, about 55% to about 80%, about 55% to about 75%, about 55% to about 70%, about 55% to about 65%, about 55% to about 60%, about 60% to about 99%, about 60% to about 95%, about 60% to about 90%,About 60% to about 85%, about 60% to about 80%, about 60% to about 75%, about 60% to about 70%, about 60% to about 65%, about 65% to about 99%, about 65% to about 95%, about 65% to about 90%, about 65% to about 85%, about 65% to about 80%, about 65% to about 75%, about 65% to about 70%, about 70% to about 99%, about 70% to about 95%, about 70% to about 90%, about 70% to about 85%, about 70% to about 80%, about 70% to about 75%, about 75% to about 99%, about 75% to about 95%, about 75% to about 90%, about 75% to about 85%, about 75% to about 80%, about resulting in improved cardiac contractile function as measured by longitudinal global strain (GLS) of 80% to about 99%, about 80% to about 95%, about 80% to about 90%, about 80% to about 85%, about 85% to about 99%, about 85% to about 95%, about 85% to about 90%, about 90% to about 99%, about 90% to about 95%, or about 95% to about 99% reduction (e.g., when compared to the GLS in a human subject prior to administration (e.g., when administered using any of the exemplary dosages and / or frequencies described herein),

[0204] In some embodiments, administering the fragment or antigen-binding fragment thereof increases the IL-18 expression level by at least about at least about 0.5%, at least about 1%, at least about 1.5%, at least about 2%, at least about 2.5%, at least about 3%, at least about 3.5%, at least about 4%, at least about 4.5%, at least about 5%, at least about 6%, at least about 7%, at least about 8%, at least about 9%, at least about 10%, at least about 11%, at least about 12%, at least about 13%, at least about 14%, at least about 15%, at least about 16%, at least about 17%, at least about 18%, at least about 19%, at least about 20%, at least about 21%, at least about 22%, at least about 23%, at least about 24%, at least about 25%, at least about 26%, at least about 27%, at least about 28%, at least about 29%, at least about 30%, at least about 31%, at least about 32%, at least about 33%, at least about 34%, at least about 35%, at least about 36%, at least about 37%, at least about 38%, at least about 39%, at least about 40%, at least about 41%, at least about 42%, at least about 43%, at least about 44%, at least about 45%, at least about 46%, at least about 47%, at least about 48%, at least about 49%, at least about 50%, at least about 51%, at least about 52%, at least about 53%, at least about 54%, at least about 55%, at least about 56%, at least about 57%, at least about 58%, at least about 59%, at least about 60%, at least about 61%, at least about 62%, at least about 63%, at least about 64%, at least about 6 at least about 17%, at least about 18%, at least about 19%, at least about 20%, at least about 21%, at least about 22%, at least about 23%, at least about 24%, at least about 25%, at least about 26%, at least about 27%, at least about 28%, at least about 29%, at least about 30%, at least about 31%, at least about 32%, at least about 33%, at least about 34%, at least about 35%, at least about 36%, at least about 37%, at least about 38%, at least about 39%, at least about 40%, at least about 41%, At least about 42%, at least about 43%, at least about 44%, at least about 45%, at least about 46%, at least about 47%, at least about 48%, at least about 49%, at least about 50%, at least about 51%, at least about 52%, at least about 53%, at least about 54%, at least about 55%, at least about 56%, at least about 57%, at least about 58%, at least about 59%, at least about 60%, at least about 61%, at least about 62%, at least about 63%, at least about 64%, at least about 65%, at least about 66%, at least about 67%, at least about 68%, at least about 69%, at least about 70%, at least about 71%, at least about 72%, at least about 73%, at least about 74%, at least about 75%, at least about 76%, at least about 77%, at least about 78%, at least about 79%, at least about 80%, at least about 81%, at least about 82%, at least about 83%, at least about 84%, at least about 85%, at least about 86%, at least about 87%, at least about 88%, at least about 89%, at least about 90%, at least about 91%,results in improved cardiac contractile function as measured by longitudinal global strain (GLS) of at least about 92%, at least about 93%, at least about 94%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, or at least about 99% (e.g., when administered using any of the exemplary dosages and / or frequencies described herein);

[0205] In some embodiments, administering the fragment or antigen-binding fragment thereof may result in an increase in the expression of at least about 0.1%, at least about 0.2%, at least about 0.3%, at least about 0.4%, at least about 0.5%, at least about 0.6%, at least about 0.7%, at least about 0.8%, at least about 0.9%, at least about 1%, at least about 1.1%, at least about 1.2%, at least about 1.3%, at least about 1.4%, at least about 1.5%, at least about 1.6%, at least about 1.7%, at least about 1.8%, at least about 1.9%, at least about 2%, at least about 2.1%, at least about 2.2%, at least about 2.3%, at least about 2.4%, at least about 2.5%, at least about 2.6%, at least about 2.7%, at least about 2.8%, at least about 2.9%, at least about 3.0%, at least about 3.1%, at least about 3.2%, at least about 3.3%, at least about 3.4%, at least about 3.5%, at least about 3.6%, at least about 3.7%, at least about 3.8%, at least about 3.9%, at least about 4. 4%, at least about 4.1%, at least about 4.2%, at least about 4.3%, at least about 4.4%, at least about 4.5%, at least about 4.6%, at least about 4.7%, at least about 4.8%, at least about 4.9%, or at least about 5%) of improved cardiac contractile function as measured by a GLS of at least about 2.8%, at least about 2.9%, at least about 3%, at least about 3.1%, at least about 3.2%, at least about 3.3%, at least about 3.4%, at least about 3.5%, at least about 3.6%, at least about 3.7%, at least about 3.8%, at least about 3.9%, at least about 4%, at least about 4.1%, at least about 4.2%, at least about 4.3%, at least about 4.4%, at least about 4.5%, at least about 4.6%, at least about 4.7%, at least about 4.8%, at least about 4.9%, or at least about 5%) (e.g., when administered using any of the exemplary dosages and / or frequencies described herein).

[0206] The antibody formulation may be administered intravenously or subcutaneously at a dosage range of about 0.5 mg / kg to about 30 mg / kg of host body weight. For example, the dosage may be about 0.5 mg / kg body weight, about 1.0 mg / kg, about 1.5 mg / kg, about 2.0 mg / kg, about 4.0 mg / kg, about 5.0 mg / kg, about 8.0 mg / kg, about 10 mg / kg, about 15 mg / kg, about 16 mg / kg, about 20 mg / kg, about 24 mg / kg, about 25 mg / kg, or about 30 mg / kg body weight. The dosage may also be administered according to body surface area from about 0.5 mg / m2 to about 500 mg / m2, for example, 0.5, 5, 10, 50, 100, 250, or 500 mg / m2. For intravenous dosing, an amount of antibody formulation sufficient to achieve the desired dosage for an individual patient is transferred from one or more vials into one or more intravenous bags containing fluid (e.g., saline) and administered to the patient.

[0207] Antibodies are usually administered multiple times. Exemplary treatment regimens require administration once every two weeks, once a month, or once every three to six months. For example, a patient may receive an antibody formulation once every four weeks, for example, every 28 days. The frequency of dosing may be adjusted depending on the pharmacokinetic profile of the antibody formulation in the patient. For example, the half-life of the antibody may warrant a two-week frequency of dosing. In some embodiments, the pharmaceutical formulation is administered intravenously every 28 days at an antibody dosage of about 24 mg / kg. For example, some patients may receive an intravenous dose of about 24 mg / kg virutamimab every 28 days. For example, some patients may receive an intravenous dose of about 24 mg / kg virutamimab every 28 days (± 5 days). In certain embodiments, a minimum of 21 days between doses is required. For some such patients, the virutamimab formulation transferred to the intravenous bag was initially reconstituted from a lyophilized formulation to a formulation having a pH of about 6.5 and containing about 50 mg / ml virutamimab, about 25 mM histidine buffer, about 230 mM trehalose, and about 0.2 g / L polysorbate 20. The desired dose for some patients may be administered subcutaneously undiluted from a vial containing any of the formulations disclosed herein.

[0208] In some embodiments disclosed herein, the antibody is administered to the patient for at least 8 months, at least 9 months, at least 10 months, at least 11 months, at least 12 months, at least 13 months, at least 14 months, at least 15 months, at least 16 months, at least 18 months, at least 19 months, at least 20 months, at least 21 months, at least 22 months, at least 23 months, at least 24 months or even longer.For example, the pharmaceutical preparation is administered to the patient for a duration effective to achieve or maintain an improvement in health status as indicated by an increase in 6MWT or SF-36v2 PCS score, or for a duration long enough to achieve or maintain a lower risk of mortality compared to untreated patients.For some patients, the lower risk may be established after at least 8 months of treatment.For some patients, the lower risk may be established after at least 9 months of treatment.For some patients, the lower risk may be established after at least 12 months of treatment or after at least 18 months of treatment or after 24 months of treatment. For these patients, the lower risk of mortality correlates with longer survival compared to untreated patients.

[0209] Also disclosed herein is a combination therapy for treating or preventing AL amyloidosis. Such combination therapy is carried out by administering the antibody formulation disclosed herein in combination with one or more second therapeutic agents, such as another treatment for treating or preventing AL amyloidosis. The combination therapy disclosed herein may be carried out in combination with a second treatment, and is used to treat or prevent diseases or conditions associated with amyloid disease, such as inflammatory disease, chronic microbial infection, neoplasm (including malignant neoplasm), inherited inflammatory disease, and / or lymphoproliferative disorder. Numerous treatments are available commercially and in clinical evaluation and preclinical development, any of which may be selected for use in combination with the antibody formulation of the present disclosure. Such treatments fall into several major categories, including, but not limited to: (i) nonsteroidal anti-inflammatory drugs (NSAIDs; e.g., detoprofen, diclofenac, diflunisal, etodolac, fenoprofen, flurbiprofen, ibuprofen, indomethacin, ketoprofen, meclofenameate, mefenamic acid, meloxicam, nabumeone, naproxen sodium, oxaprozin, piroxicam, sulindac, tolmetin, celecoxib, rofecoxib, aspirin, choline salicylate, salsalte, and sodium and magnesium salicylates); (ii) steroids (e.g., choline salicylate, salsalte, and sodium and magnesium salicylates); (iii) DMARDs, i.e., disease-modifying antirheumatic drugs (e.g., cyclosporine, azathioprine, methotrexate, leflunomide, cyclophosphamide, hydroxychloroquine, sulfasalazine, D-penicillamine, minocycline, and gold); (iv) recombinant proteins (e.g., ENBREL® (etanercept, a soluble TNF receptor) and REMICADE® (infliximab) chimeric monoclonal anti-TNF antibody); (v) stem cell transplantation; and / or (vi) chemotherapy.Patients with AL amyloidosis may receive treatment regimens that include drugs or drug combinations often used to treat hematological malignancies, such as melphalan, prednisone, dexamethasone, lenalidomide (REVLIMID®), proteosome inhibitors such as bortezomib (VELCADE®) and carfilzomib (KYPROLIS®), and CD38 agents, at dosages in the standard of care range.

[0210] When combination therapy is practiced, two or more drug substances are administered simultaneously or sequentially in any order, i.e., the formulations disclosed herein are administered prior to administration of the second drug substance, simultaneously with the second drug substance, or subsequent to administration of the second drug substance. For example, the combination therapy may be performed by administering the first treatment prior to (e.g., 1 minute, 5 minutes, 15 minutes, 30 minutes, 45 minutes, 1 hour, 2 hours, 4 hours, 6 hours, 12 hours, 24 hours, 48 ​​hours, 72 hours, 96 hours, 1 week, 2 weeks, 3 weeks, 4 weeks, 5 weeks, 6 weeks, 8 weeks, or 12 weeks before), simultaneously with, or subsequently to (e.g., 1 minute, 5 minutes, 15 minutes, 30 minutes, 45 minutes, 1 hour, 2 hours, 4 hours, 6 hours, 12 hours, 24 hours, 48 ​​hours, 72 hours, 96 hours, 1 week, 2 weeks, 3 weeks, 4 weeks, 5 weeks, 6 weeks, 8 weeks, or 12 weeks after) administration of the second agent / treatment (e.g., daratumumab).

[0211] The dosage, frequency and mode of administration of each component of the combination may be independently controlled. For example, one therapeutic agent / treatment may be administered orally three times a day, while the second therapeutic agent / treatment may be administered intramuscularly once a day. The combination therapy may be given in an on-off cycle with a drug holiday. The compounds may be mixed or otherwise formulated together such that one administration delivers both compounds. In this case, each therapeutic agent is generally present in an amount of 1-95% by weight of the total weight of the composition. Alternatively, the antibody formulations disclosed herein and the second therapeutic agent may be formulated separately in individual dosages. The drug combination for treatment may be provided as a component of a pharmaceutical package.

[0212] Preferably, the combination therapy of the present disclosure produces a synergistic therapeutic effect, i.e., an effect that is greater than the sum of their individual effects or therapeutic outcomes. Measurable therapeutic outcomes are described herein. For example, a synergistic therapeutic effect may be at least about 2-fold greater, or at least about 5-fold greater, or at least about 10-fold greater, or at least about 20-fold greater, or at least about 50-fold greater, or at least about 100-fold greater than the sum of the therapeutic effects produced by the single agents of a given combination. A synergistic therapeutic effect may also be observed as an increase in therapeutic effect of at least 10%, or at least 20%, or at least 30%, or at least 40%, or at least 50%, or at least 60%, or at least 70%, or at least 80%, or at least 90%, or at least 100% or more compared to the sum of the therapeutic effects produced by the single agents of a given combination. A synergistic effect is also an effect that allows the dosage of therapeutic agents to be reduced when used in combination.

[0213] Some methods of the disclosure include treating a subject with AL amyloidosis by determining one or more of the following prognostic indicators: (1) the patient's Mayo stage of AL amyloidosis, (2) the patient's six-minute walk distance (6MWT) and ejection fraction (EF) and / or the patient's Mayo stage and EF. Once prognostic indicator(s) is determined, the patient is selected for treatment if it meets one of the following treatment criteria: (1) has Mayo stage IV AL amyloidosis; (2) has 6MWT≧30 meters and ≦550 meters; (3) has 6MWT≧150 meters and EF>50% at baseline; (4) has Mayo stage IV and 6MWT≧30 meters and ≦550 meters; (5) has Mayo stage IV and EF>50% at baseline; (6) has Mayo stage IV, 6MWT≧150 meters and EF>50% at baseline, (7) has cardiac complications; (8) has Mayo stage IV AL amyloidosis and has cardiac complications; or (9) has Mayo stage IV AL amyloidosis, cardiac complications, and 6MWT≧30 meters and ≦550 meters. Treatment includes administering an effective dose of one or more antibodies disclosed herein.

[0214] In one method of the disclosure, patients who meet one or more prognostic indicators are treated with virutamimab (24 mg / kg) supplied as a sterile, lyophilized dosage form in 20 / 25 mL vials containing 500 mg virutamimab. Each vial is reconstituted with 9.6 mL of sterile water for injection (WFI) to a concentration of 50 mg / mL, resulting in a buffered, isotonic, preservative-free solution. Vilutamimab is administered once every 28 days as an initial 120 (± 10) minute IV infusion. If the subject tolerates the initial infusion, subsequent infusions may be administered over 60 (± 10) minutes. Doses are administered at intervals of at least 21 days.

[0215] Patients may be treated with concurrent standard of care chemotherapy, which may include, for example, bortezomib administered subcutaneously every week. In some embodiments, concomitant treatments are not permitted, including: other investigational drugs (e.g., drugs not approved for any indication), myeloablative chemotherapy with ASCT, organ transplantation, and doxycycline. In some embodiments, steroids are not permitted prior to enrollment in a clinical trial for the treatment of AL amyloidosis. In some embodiments, initiation of daratumumab treatment at any time other than the time of randomization is prohibited. EXAMPLES

[0216] The following examples are included to illustrate the modes disclosed herein. Certain aspects of the following examples are described in terms of the techniques and procedures discovered or contemplated by the present co-inventors to fully implement the practices disclosed herein. In light of this disclosure and the general level of skill of those skilled in the art, it will be understood that the following examples are intended to be illustrative only, and that numerous changes, modifications and alterations may be used without departing from the scope of the present disclosure.

[0217] Example 1 A Phase 3, Randomized, Multicenter, Double-Blind, Placebo-Controlled, Efficacy and Safety Study of Virutamimab Plus Standard Therapy Versus Placebo Plus Standard Therapy in MAYO Stage IV Subjects With Light-Chain (AL) Amyloidosis The primary objective of the study (NEOD001-301) is to evaluate the efficacy of virutamimab plus standard of care when administered intravenously to Mayo stage IV subjects with AL amyloidosis by assessing time to all-cause mortality. Secondary objectives are to evaluate virutamimab plus standard of care on: (1) change from baseline to 9 months in 6-minute walk test (6MWT) distance (meters), and (2) change from baseline to 9 months in health-related quality of life using the Short Form 36 Questionnaire (SF-36v2).

[0218] Newly diagnosed, Mayo stage IV subjects with AL amyloidosis will receive local standard of care chemotherapy plus virutamimab. The initial first-line chemotherapy regimen must include bortezomib. Subjects will be stratified at randomization based on their 6MWT distance (<300 meters vs. ≥300 meters) and initiation of daratumumab treatment at randomization (yes vs. no).

[0219] Subjects remain in the study until study completion, which occurs when approximately 47 primary endpoint events (mortality from any cause) are reached. The primary endpoint is time to mortality from any cause. Survival distributions are compared between treatment groups using the log-rank test.

[0220] An interim analysis will be performed when approximately 50% of events have occurred (24). The O'Brien-Fleming group sequential method will be used to split the study-wide significance level between the interim analysis (p=0.0108) and the final analysis (p=0.0984). If overwhelming efficacy (p<0.0108) is achieved at the interim analysis, the study will be stopped early.

[0221] If a subject discontinues the investigational drug before the end of the study but is willing to continue participating in study visits, the subject should have an Early Treatment Discontinuation (ETD) visit within 28-35 days after the last study drug administration and then be evaluated every 3 months (see Table 2). All visits after the ETD visit should occur as scheduled, i.e., at the times that the visits would have occurred if the subject had remained on the investigational drug.

[0222] Subject screening will occur 28 days prior to the first dose of study drug on Month 1, Day -1. The screening period may be extended with approval by the Medical Monitor. Screening assessments are listed in Table 1 herein.

[0223] Two screening 6MWTs are required prior to the first dose of study drug. The first screening 6MWT should be performed between days -28 and 5, within 3 days prior to month 1 (i.e., days 3-1), and at least 4 days prior to the second screening 6MWT. The post-baseline 6MWT may be performed on the same day as study drug administration and must be completed prior to study drug infusion. If all eligibility requirements are met, the month 1 day 1 assessment is completed and treatment begins. Each visit is noted with the first study drug infusion date as month 1 day; subsequent months are noted by their "month" and "day" using sequential numbers (e.g., the second dose is administered on month 2 day 1). "Cycles" are reserved to note chemotherapy administration. Assessment and visit windows are listed in the event schedule (Table 1). All doses of study drug will be administered at the study site starting on the day of randomization, every 28 days (± 2 days for months 1 through 3, and ± 5 days for all months thereafter) from the previous month X-day-1 visit until the EOT / ETD visit. For months 1 through 3, subjects will be evaluated weekly, although not all visits need to be at the study site. For month 3 and all subsequent months until the end of the study, subjects will only need to return to the study site every 28 days for Day 1 dosing of study drug.

[0224] First-line chemotherapy must be a bortezomib-containing regimen, with bortezomib administered subcutaneously (SC) weekly. The first dose of daratumumab-containing chemotherapy for subjects stratified to start bortezomib and daratumumab at randomization will be administered after Month 1 Day 1 study drug administration (after the post-study drug infusion observation period) such that Month 1 Day 1 of the study is the same as Cycle 1 Day 1 of chemotherapy. In addition to the visits outlined above, during the first cycle of chemotherapy, subjects must return to the study site for each weekly dose of bortezomib and for pre-dose evaluations. During the second and third cycles of chemotherapy, bortezomib must be administered at the study site during the Month 2 Day 1, Month 2 Day 15, and Month 3 Day 1 visits (i.e., Cycle 2 Day 1, Cycle 2 Day 15, and Cycle 3 Day 1, respectively). If for any reason in the investigator's opinion the subject should continue to come to the study site weekly (e.g., toxicity beyond the expected side effects of chemotherapy), the other cycle 2 and cycle 3 weekly bortezomib administrations may be administered at the study site as well. At the investigator's discretion, if the subject does not experience any unexpected or significant toxicity, the subject may receive cycle 2 days 8 and 22 and cycle 3 days 8, 15 and 22 bortezomib by their local physician rather than by the investigator. Within one day prior to or on the day of each administration of bortezomib by the local physician, a medical professional must obtain pre-dose vital signs and central laboratory samples. However, if bortezomib is administered on a Monday (or there is a holiday in between), it is acceptable to perform a homecare visit on the preceding Friday.

[0225] If a bortezomib dose is missed, chemotherapy cycles may not be aligned with monthly study drug dosing. In this case, weekly visits during months 1 through 3 should continue as described above to closely monitor the subject's health during the first month of concurrent chemotherapy. Throughout the study, monthly doses of study drug should not be delayed or skipped due to adjustments made for chemotherapy dosing.

[0226] Safety and efficacy assessments will be performed at each visit.

[0227] Autologous stem cell transplantation is not permitted during the study.

[0228] Inclusion Criteria (subjects must meet all of the following criteria): 1. Age ≥ 18 years and legal age of consent according to local regulations 2. Newly diagnosed, AL amyloidosis treatment naïve 3. Bone marrow demonstrates clonal plasma cells 4. Confirmed diagnosis of AL amyloidosis by: Histochemical diagnosis of amyloidosis as determined by polarized light microscopy of green birefringent material in Congo red-stained tissue specimens or characteristic electron microscopic findings And Confirmatory immunohistochemistry or mass spectrometry for AL amyloidosis 5. If the subject is any of the following: · be black or of African descent; Age over 75 years with concomitant monoclonal hypergammaglobulinemia, - History of familial amyloidosis with concomitant monoclonal hypergammaglobulinemia; and If there is no tissue available for classification determination and the subject meets the criteria of having biopsy-diagnosed amyloidosis with echocardiographic evidence of amyloidosis and monoclonal hypergammaglobulinemia, the subject must have gene sequencing consistent with transthyretin (TTR) wild type (i.e., no TTR mutations are present) and technetium-99m-3,3-diphosphono-1,2 propanodicarboxylic acid ( 99m Tc DPD; Rapezzi 2011), hydroxymethylene diphosphonate ( 99m Tc HMDP; Galat 2015) or pyrophosphate ( 99mTc PYP; Bokhari 2013) scintigraphy must have a score of 0 6. Cardiac complications as defined by all of the following: Previously described or currently documented clinical signs and symptoms supporting the diagnosis of heart failure in the definitive diagnosis of AL amyloidosis in the absence of an alternative explanation for heart failure Either an endomyocardial biopsy demonstrating AL amyloidosis or an echocardiogram demonstrating a mean left ventricular wall thickness >12 mm in diastolic time that would adequately describe the degree of wall thickening in the absence of other causes (e.g., severe hypertension, aortic stenosis) 7. Below: NT-proBNP ≥ 1800 pg / mL, and Troponin-T ≥ 0.025ng / mL (mcg / L) or high-sensitivity cardiac troponin T ≥ 40ng / L, and dFLC ≥ 18 mg / dL Confirmed Mayo stage IV as defined by 8. Planned first-line chemotherapy contains bortezomib administered subcutaneously (SC) weekly 9. Adequate bone marrow reserve, liver function and renal function as demonstrated by: Absolute neutrophil count (ANC) ≥ 1.0 × 109 cells / L; · Platelet count ≧75×109 / L, Hemoglobin ≥ 9g / dL, Total bilirubin ≤ 2x upper limit of normal (xULN), (except in subjects with Gilbert syndrome, in which case direct bilirubin ≤ xULN) Aspartate aminotransferase (AST) / serum glutamic oxaloacetic transaminase (SGOT) ≤ 3 × ULN Alanine aminotransferase (ALT) / serum glutamic pyruvic transaminase (SGPT) ≤ 3 × ULN Alkaline phosphatase (ALP) ≤ 5 x ULN (excluding subjects with hepatomegaly and isoenzymes specific to liver rather than bone) Estimated glomerular filtration rate (eGFR) ≥ 30 mL / min / 1.73 m2 as estimated by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula 10. Sitting systolic blood pressure: 90-180mmHg 11. 6MWT walking distance ≥ 30 meters and ≤ 550 meters at each screening 12. Women of childbearing potential (WOCBP) must have two negative pregnancy tests at screening, the second within 24 hours prior to the first dose of study drug, and agree to use highly effective physician-approved contraception from screening through 90 days after the last dose of study drug. 13. Male subjects must be surgically sterile or agree to use barrier methods in conjunction with the use of highly effective physician-approved contraception by their fertile female partner from screening through 90 days after the last study drug dose. 14. Ability to understand and willingness to sign an informed consent form prior to the start of all study procedures.

[0229] Exclusion Criteria (subjects must not meet any of the following criteria): 1. Non-AL amyloidosis 2. NT-proBNP>8,500pg / mL 3. Meets the International Myeloma Working Group (IMWG) definition of multiple myeloma, except for malignant biomarkers, with involved / uninvolved serum free light chain ratio ≥ 100 4. Subject is eligible to undergo and plans to undergo ASCT or organ transplant during the study 5. Symptomatic orthostatic hypotension that, in the investigator's medical judgment, interferes with the subject's ability to safely undergo procedures or complete study assessments. 6. Electrocardiogram (ECG) evidence of myocardial infarction, uncontrolled angina, severe uncontrolled ventricular arrhythmia, or acute ischemia within 6 months prior to the 1st month visit 7. Severe valvular stenosis (e.g., aortic or mitral stenosis with valve area <1.0 cm2) or severe congenital heart disease 8. ECG evidence of acute ischemia or active conduction system abnormality with any of the following exceptions: 1st degree AV block 2nd degree AV-block type 1 (Mobitz type 1 / Wenckebach type) Right or left bundle branch block Atrial fibrillation with controlled heart rate (uncontrolled [>110 bpm] heart rate is not permitted [determined by average of 3 beats in Lead II or 3 representative beats if Lead II does not represent the entire EKG]) 9. Peripheral neuropathy rated as National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) Grade 2, Grade 3, or Grade 4 with pain 10.Subject has received oral or IV antibiotics, antifungals, or antivirals, excluding prophylactic oral agents, within 1 week of the first day of the month 11. Prior treatment with hematopoietic growth factors, blood, or blood product transfusions within 1 week of Month 1 12. Prior radiation therapy within 4 weeks of day 1 of month 1 13. Major surgery within 4 weeks of Month 1 or planned major surgery during the study 14. Active malignancies with the exception of any of the following: Appropriately treated basal cell carcinoma of the skin, squamous cell carcinoma or in situ cervical carcinoma Adequately treated stage I cancer in which the subject is currently in remission and has been in remission for 2 years Low-risk prostate cancer with a Gleason score <7, prostate-specific antigen <10mg / mL, and cancer stages up to cT2a, cN0, and CM0 Any other cancer in which the subject has been disease-free for ≥2 years 15. History of severe allergy to any of the components of virutamimab, such as histidine / L-histidine hydrochloride monohydrate, trehalose dehydrate, or polysorbate 20, or history of grade ≥ 3 infusion-related AE or hypersensitivity to another monoclonal antibody or known hypersensitivity to diphenhydramine (or H1 antihistamine equivalent) or acetaminophen (or its equivalent, paracetamol). 16. Known, non-resolved, or active HIV, Hepatitis B, Hepatitis C or SARS-CoV-2 infection 17. Pretreatment with plasma cell-directed chemotherapy, virutamimab, daratumumab, 11-1F4, anti-serum amyloid P antibodies, doxycycline against amyloid or other investigational treatments directed against amyloid 18. Treatment with another investigational drug within 30 days of Month 1 19. Pregnant or breastfeeding women 20. Any condition that may interfere with the conduct of the study, or the procedure therefor may interfere with the conduct of the study, or which in the investigator's opinion unacceptably increases the risk to the subject from participation in the study. 21. The subject is under legal control 22. History of epilepsy or seizure disorder except for febrile convulsions in childhood 23. Waldenström hypergammaglobulinemia and / or Immunoglobulin M (IgM) monoclonal hypergammaglobulinemia

[0230] Dosage, Administration, and Schedule Investigational Medications: Investigational medications consist of intravenous virutamimab or placebo. Virutamimab dose is 24 mg / kg; however, the maximum dose administered will not exceed 2500 mg. Thus, subjects weighing 104.2 kg or more will receive the maximum dose of 2500 mg.

[0231] Virutamimab (24 mg / kg) is supplied as a sterile lyophilized dosage form in 20 / 25 mL vials containing 500 mg virutamimab. Each vial is reconstituted with 9.6 mL sterile water for injection (WFI) to a concentration of 50 mg / mL, resulting in a buffered, isotonic, preservative-free solution. The investigational product will be administered once every 28 days as an initial 120 (± 10) minute IV infusion. If the subject tolerates the initial infusion, subsequent infusions may be administered over 60 (± 10) minutes. The length of the infusion may be extended to a longer period if clinically indicated. A minimum of 21 days is required between doses.

[0232] Premedication: All subjects will be premedicated for each dose of study drug with 25 mg diphenhydramine (or equivalent dose of H1 antihistamine) and 650 mg acetaminophen (or equivalent dose of paracetamol according to local practice) within 30-90 minutes prior to study drug administration.

[0233] Standard of care chemotherapy: All subjects will receive concurrent standard of care chemotherapy, which must include bortezomib administered subcutaneously weekly for the initial first-line chemotherapy regimen. Subsequent chemotherapy regimens may be prescribed as standard of care at the investigator's discretion. Bortezomib should be administered according to approved prescribing information and local site practice. The initial first-line chemotherapy regimen may also include daratumumab. Initiation of daratumumab treatment at the time of randomization is permitted at the investigator's discretion; initiation at any other time during the study is prohibited. If chemotherapy, which may include daratumumab, is administered on the same day as the investigational drug, chemotherapy must be administered after completion of administration of the investigational drug. Antiviral prophylaxis is required.

[0234] Efficacy Endpoints Primary efficacy endpoint: time to all-cause mortality.

[0235] Secondary efficacy endpoints: change from baseline to 9 months in 6MWT distance (meters); change from baseline to 9 months in SF-36v2 physical component summary (PCS) score.

[0236] Statistical considerations Analysis Populations. The intention to treat (ITT) and safety populations will include all randomized subjects with Mayo stage IV AL amyloidosis who receive either amount of investigational drug (virutamimab or placebo). The ITT population will be the primary population used for efficacy analyses. The safety population will be the primary population used for safety analyses.

[0237] Efficacy analysis. Interim Analysis - An interim analysis will be performed when approximately 50% (or 24) events have occurred. Using the O'Brien-Fleming group sequential method, an overall significance level of 0.10 will be split between the interim analysis (p<0.0108) and the final analysis (p<0.0984). The results of the interim analysis will be evaluated to determine whether the trial can be stopped early for overwhelming efficacy.

[0238] Primary Analysis - The primary endpoint is time to all-cause mortality. All-cause mortality will include all deaths occurring after the first infusion of study drug (i.e., Study Day 1) through the last visit of the last subject in the study.

[0239] The distribution of time to all-cause mortality will be summarized using the Kaplan-Meier method. Virutamimab will be compared to placebo using the log-rank test and stratified by initiation of daratumumab treatment at randomization. Sensitivity analyses using the unstratified log-rank test may also be performed.

[0240] Hazard ratios, 90% CIs, and 95% CIs are determined based on Cox regression models stratified by initiation of daratumumab use at randomization.

[0241] The log-rank test will be used to compare virutamimab and placebo controls at a significance level of 0.0984 in the final analysis. Secondary Efficacy Analyses - Evaluate the following secondary endpoints: Change from baseline to month 9 in 6MWT distance (meters) Change from baseline to month 9 in SF-36v2 PCS score

[0242] Changes in 6MWT distance (meters) from baseline to month 9 will be analyzed using a restricted maximum likelihood (REML) based mixed-effect model for repeated measures (MMRM) model, including fixed effects for randomization stratification (<300 meters vs. ≥300 meters) and treatment group, categorical time points and treatment group x time point interactions, with baseline value included as a covariate.

[0243] SF-36v2 PCS score change from baseline to Month 9 will be analyzed using an aREML-based MMRM model with fixed effects for treatment group, categorical time points, and treatment group x time point interactions, with baseline values ​​included as covariates. An unstructured covariance model will be used. [Table 1-1] [Table 1-2] BP = blood pressure; ECG = electrocardiogram; EOI = end of infusion; EOT = end of treatment; ETD = early treatment discontinuation; HR = heart rate; NT-proBNP = N-terminal pro-brain natriuretic peptide; NYHA = New York Heart Association; PE = physical examination; SAE = serious adverse events; sFLCs = serum free light chains; 6MWT = 6-minute walk test; SF-36v2 = Short Form 36 version 2; WOCBP = women of childbearing potential 1The 28-day screening period may be extended with approval by the Medical Monitor. Individual test results not meeting eligibility requirements may be repeated, with the exception of the 6MWT; rescreening is permitted once per subject. 2 Bortezomib-containing chemotherapy on cycle days 2-8 and 22 and cycle days 3-8, 15 and 22 should be administered at the study site by the investigator if the subject had significant toxicity, otherwise may be administered by a local physician at the investigator's discretion. See footnote 25 for further details. 3 The EOT / ETD visit will occur 28-35 days after the last dose of study drug. 4 At the first screening visit, a comprehensive cardiac, hematological and oncological medical history is obtained; in addition, for all other conditions, relevant medical history for the past 5 years (including any major hospitalizations and surgeries), and the subject's current medical condition are obtained. At the second screening visit, any changes / additions to the medical history from the first screening visit are assessed. 5 Mass spectrometry tissue typing, immunoelectron microscopy, gene sequencing and / or 99m Results from Tc scintigraphy must be available prior to randomization to assess eligibility for subjects specified in inclusion criterion #5. 6 At visits where the SF-36v2 is administered, the SF-36v2 should be administered prior to the administration of any other study assessments that day. 7 If an echocardiogram is performed within 90 days prior to Screening Day -28, it does not need to be repeated at Screening and the previous result may be used for eligibility. After Screening, within the study visit window, perform an echocardiogram on Day 1 or within 10 days prior thereto every 6 months; if not performed within 60 days prior to visit, repeat at EOT / ETD. 8ECGs will be performed three times as follows: Month 1, Day 1: within 45 minutes pre-dose and 1 hour (± 15 minutes) after EOI; and for each Day 1 visit for each month, within 45 minutes pre-dose or any time on non-infusion days. Medications given for prevention of chemotherapy-induced side effects should not be administered prior to completion of the post-infusion ECG. 9 A thorough PE examination will include height (screening only), weight, and examination of: general appearance; head, ears, eyes, nose and throat; neck; skin; cardiovascular system; respiratory system; gastrointestinal system; and nervous system. Evaluate macroglossia, submandibular lymph nodes / distention, gland enlargement, ecchymosis, liver / spleen size (palpable + / -), ascites (+ / -), and edema (which should be quantified on a scale of 0 to 4). 10 Symptom-based PE should be as clinically indicated and also include assessment of body weight and macroglossia, submandibular lymph nodes / distention, gland enlargement, ecchymosis, liver / spleen size (palpable + / -), ascites (+ / -) and edema (which should be quantified on a scale of 0-4). 11 SARS-CoV-2 testing should be performed once within 14 days prior to dosing on Day 1, either at the first or second screening visit. 12 Local laboratory results for hematology and chemistry will be used for subject management and should be reviewed for safety assessment prior to administration of chemotherapy, but will not be collected in electronic case report forms or clinical databases. 13 Only performed if the subject returns to the study site for this visit. 14 Day 1 of Month 1. Use a local laboratory for a serum / urine pregnancy test within 24 hours prior to study drug administration. 15 Local laboratory serum / urine pregnancy test results are obtained prior to study drug administration. 16 If performed on the same day, central laboratory samples were collected prior to the 6MWT. 17 Prothrombin time / international normalized ratio and partial thromboplastin time were collected at each time point. 18 NT-proBNP should be collected prior to the 6MWT if performed on the same calendar day. 19 Subjects should be scheduled to return to the same clinic for each 6MWT from Screening 1 through Month 9 and at EOT / ETD. Post-baseline 6MWTs may be performed on the same calendar days that study drug is administered (i.e., Months 3, 6, and 9), as long as the NT-proBNP sample is collected before the 6MWT is performed and the 6MWT is completed before the start of the study drug infusion. BP and HR will be collected before and after the 6MWT. 20 The first screening 6MWT must be performed between days -28 and -5, and at least 4 days apart from the second screening 6MWT, which should be performed within 3 days prior to the Month 1 visit (i.e., days -3 to -1). 21 Randomization via the Interactive Voice and Web Response System (IXRS) can occur up to 1 day prior to the Month 1 -Day 1 visit. 22 All subjects receive 25 mg diphenhydramine (or an equivalent dose of an H1 antihistamine) and 650 mg acetaminophen (or an equivalent dose of paracetamol according to local practice) within 30-90 minutes prior to the start of the infusion. 23 Vital signs include BP, HR, respiratory rate and temperature; are assessed in the same position for all time points after the subject has rested for ≥5 minutes. Pre-dose assessment of vital signs should be performed after administration of premedication. Screening and non-infusion days: Any time; Month 1 Day: Within 30 minutes before dosing, midway through the infusion (i.e., approximately 60 minutes after the start of the infusion), immediately at EOI (+10 minutes), 0.5 hours (±10 minutes) and 1 hour (±10 minutes) after EOI. All other months Day 1: Within 30 minutes before dosing, EOI (+10 minutes) and 1 hour (±10 minutes) after EOI. 24Subjects should be closely monitored for 90 (± 10) minutes after completion of the investigational drug infusion. The investigator may extend this standard monitoring time if he deems appropriate or in accordance with local standards. In the event of any clinical problems or suspicious signs or symptoms after the infusion, the subject will remain under observation for as long as the investigator deems appropriate. 25 First-line chemotherapy must be a bortezomib-containing regimen with bortezomib administered subcutaneously weekly according to the approved prescribing information and local site practice. The initial first-line chemotherapy regimen may also include daratumumab at the investigator's discretion. Antiviral prophylaxis is required. If chemotherapy is administered on the same day as the study drug, chemotherapy must be administered after the post-infusion observation period. The number of first-line chemotherapy cycles and subsequent chemotherapy regimens will be administered per standard of care at the investigator's discretion. 26 Bortezomib must be administered at the study site on Cycle 1-Days 1, 8, 15, and 22; Cycle 2-Days 1 and 15; and Day 1 of subsequent cycles, following review of local laboratory results, study drug administration, and a post-infusion observation period. 27 Chemotherapy may be administered within one day prior to or on the day of each bortezomib dose on cycle 2 days 8 and 22 and cycle 3-8, 15 and 22 by the local physician with a home care visit by a Prothena sponsored health care provider to obtain vital signs, blood samples, and bioanalytical samples (if applicable) for central laboratory testing. If bortezomib is administered on a Monday, a home care visit may be conducted on the preceding Friday. If significant toxicity occurs during cycle 1, subjects must return to the study site for cycle 2 and cycle 3 visits until deemed appropriate by the investigator for local dosing. 28 New SAEs occurring beyond the EOT / ETD visit or >28 days after the last dose of study drug, whichever occurs later, will be reported to the sponsor and his / her designee only if, in the investigator's judgment, the SAE is related to any protocol intervention (i.e., related to study procedures or prior study drug exposure). 29 For all subjects who are randomized and receive a dose of study drug: A follow-up telephone call to assess vital signs will be conducted approximately 3 months after the subject's last visit and approximately every 3 months thereafter. If the subject prematurely discontinues study drug but agrees to return for study evaluations. [Table 2]

[0244] BP = blood pressure; ECG = electrocardiogram; ETD = early treatment interruption; HR = heart rate; NT-proBNP = N-terminal pro-brain natriuretic peptide; NYHA = New York Heart Association; PE = physical examination; RP = respiratory rate; 6MWT = 6-minute walk test; SF-36v2 = Short Form 36 version 2; WOCBP = women of childbearing potential

[0245] Table 2 footnotes 1. If a subject discontinues investigational drug before the end of the study but is willing to continue participating in study visits, the subject should have an ETD visit within 28-35 days after the last dose of investigational drug and then be evaluated every 3 months (i.e., at months 3, 6, 9, and 12 or whichever remains of these visits). All visits after the ETD visit should occur as scheduled, i.e., at the times that the visits would occur if the subject remained on investigational drug. 2. If the subject is willing to return to the research facility, otherwise the subject will undergo vital status. 3. The SF-36v2 will be administered prior to administration of any other study assessments on the day it is administered. 4. An echocardiogram will be performed within 10 days prior to Day 1 of Months 6 and 12. 5. ECG performed 3 times. 6. Symptom-based PE should be as clinically indicated and include assessment of body weight and macroglossia, submandibular lymph nodes / distention, gland enlargement, ecchymosis, liver / spleen size (palpable + / -), ascites (+ / -) and edema (which should be quantified on a scale of 0 to 4). 7. Obtain a local laboratory serum pregnancy test 90 (± 5) days after the last study drug dose. 8. Collect central laboratory samples prior to 6MWT if performed on the same day. 9. PT / INF and PTT were collected at each time point. 10. From Month 12 onwards, if the subject is willing to return to the study site, the following will be performed or collected every 3 months (e.g., Months 15, 18, 21): 6MWT (including pre- and post-6MWT BP and HR), adverse events, concomitant medications, general health status and details of any hospitalizations. 11. Withdraw if early samples establish the presence of anti-NEOD001 antibodies or if subject discontinues treatment due to suspected immunological reaction. 12. BP, HR, RR and temperature will be collected at any time during the visit. 13. Newly occurring SAEs beyond the EOT / ETD visit or >28 days after the last dose of study drug, whichever occurs later, will be reported to the sponsor and his / her designee only if, in the investigator's judgment, the SAE is related to any protocol intervention (i.e., related to study procedures or prior study drug exposure). 14. All hospitalizations and deaths occurring during this period must be reported to the Sponsor and his / her designee. 15. Vital status assessment will be performed approximately 3 months after the subject's last visit and approximately every 3 months thereafter.

[0246] Example 2 Change in longitudinal global strain (GLS) Left ventricular (LV) longitudinal global strain (GLS), assessed by echocardiography, is a measure of LV systolic function. GLS is a parameter reflecting LV deformation in the longitudinal direction, which is linked to the prognosis of numerous clinical conditions. GLS is reported as a negative value, with values ​​for normal function typically lower than -20%. GLS has been shown to be an independent predictor of overall survival in patients with AL amyloidosis, with patients with lower (more negative) GLS values ​​living longer than those with higher (less negative) GLS values. See Buss 2012; Chuy 2020; Salinaro 2017.

[0247] GLS is evaluated in subjects from the AFFIRM-AL study (Example 1) according to procedures known to those skilled in the art. See Buss 2012; Chuy 2020; Salinaro 2017. GLS is evaluated to determine the change from baseline to 6 months, 12 months, and end of treatment.

[0248] Descriptive statistics for GLS may include actual values, change from baseline, and percent change from baseline in GLS by treatment group at 6 months, 12 months, and end of treatment in the ITT population.

[0249] Administration of virutamimab to patients with Mayo stage IV AL amyloidosis reduces (ameliorates) GLS. Reduction in GLS in patients with Mayo stage IV AL amyloidosis receiving virutamimab predicts reduced mortality (e.g., improved survival) in such patients.

[0250] Administration of virutamimab and daratumumab to patients with Mayo stage IV AL amyloidosis reduces (improves) GLS. Reduction of GLS in patients with Mayo stage IV AL amyloidosis receiving virutamimab and daratumumab predicts reduced mortality (e.g., improved survival) in such patients.

[0251] References Buss SJ, Emami M, Mereles D, et al. Longitudinal left ventricular function for prediction of survival in systemic light-chain amyloidosis: incremental value compared with clinical and biochemical markers. J Am Coll Cardiol. 2012;60(12):1067-76. Chuy KL, Drill E, Yang JC, et al. Incremental value of longitudinal strain for predicting survival in patients with advanced AL amyloidosis. JACC CardioOncol. 2020;2(2):223-31. Salinaro F, Meier-Ewert HK, Miller EJ, et al. Longitudinal systolic strain, cardiac function improvement, and survival following treatment of light-chain (AL) cardiac amyloidosis. Eur Heart J Cardiovasc Imaging. 2017;18(9):1057-64

[0252] Sequence Listing SEQ ID NO: 01 Humanized antibody sequence containing mouse and human residues (humanized 2A4 light chain variable region version 3) [ka] SEQ ID NO: 02 Humanized antibody sequence containing mouse and human residues (humanized 2A4 heavy chain variable region version 3) [ka] SEQ ID NO: 03 2A4 VL CDR1 RSSQSLVHSTGNTYLH SEQ ID NO: 04 2A4 VL CDR2 KVSNRFS SEQ ID NO: 05 2A4 VL CDR3 SQSTHVPFT SEQ ID NO: 06 2A4 VH CDR1 GFTFNTYAMY SEQ ID NO: 07 2A4 VH CDR2 RIRSKSNNYAIYYADSVKD SEQ ID NO: 08 2A4 VH CDR3 PYSDSFAY SEQ ID NO: 09 7D8 VL CDR1 RSSLSLVHSTGNTYLH SEQ ID NO:10 Humanized antibody sequence containing mouse and human residues (humanized 2A4 kappa light chain) [ka] SEQ ID NO: 11 Humanized antibody sequence containing mouse and human residues (humanized 2A4 IgG1 heavy chain variant 1 (G1m1 allotype)) [ka] SEQ ID NO: 12 Humanized antibody sequence containing mouse and human residues (humanized 2A4 IgG1 heavy chain variant 2 (G1m3 allotype)) [ka] SEQ ID NO:13 Humanized antibody sequence containing mouse and human residues (humanized 2A4 IgG2 heavy chain) [ka] SEQ ID NO:14 11-1F4 Monoclonal antibody variable light [kappa] [ka] SEQ ID NO:15 11-1F4 Monoclonal antibody variable weight [ka] SEQ ID NO: 16 11-1F4 Monoclonal antibody CDR1 light chain RSSQSLVHRNGNYTLH SEQ ID NO: 17 11-1F4 Monoclonal antibody CDR2 light chain LVSNRFS SEQ ID NO:18 11-1F4 Monoclonal antibody CDR3 light chain FNTTYVPNT SEQ ID NO: 19 11-1F4 Monoclonal antibody CDR1 heavy chain SYGVSW SEQ ID NO: 20 11-1F4 monoclonal antibody CDR2 heavy chain VIWGDGSTNYHPNLMSRLSIS SEQ ID NO: 21 11-1F4 monoclonal antibody CDR3 heavy chain L.D.Y. SEQ ID NO:22 11-1F4 Monoclonal Antibody Variable Light [Kappa] [ka] SEQ ID NO:23 11-1F4 monoclonal antibody variable heavy [ka]

Claims

1. 1. A method of treating a patient with AL amyloidosis, comprising: administering to the patient an effective dose of an antibody which competes with 2A4 (ATCC Accession No. PTA-9662) or 7D8 (ATCC Accession No. PTA-9468) for binding to human amyloid A peptide or human kappa or lambda light chain immunoglobulins, or which competes with 11-1F4 (ATCC Accession No. PTA-105) for binding to kappa light chain immunoglobulins; and administering to the patient a therapeutically effective dose of daratumumab 5 to 90 minutes after completion of the step of administering the antibody, wherein the patient has: (a) Mayo stage IV AL amyloidosis; (b) 6-minute walking distance (6MWT) ≥ 30 meters and ≤ 550 meters; (c) 6MWT ≥ 150 meters and EF > 50%; (d) Mayo stage IV and EF>50%; (e) Mayo stage IV and 6MWT ≧30 meters and ≦550 meters; (f) Mayo stage IV and 6MWT ≥ 150 meters and EF > 50%; (g) having cardiac complications; (h) Mayo stage IV AL amyloidosis and cardiac complications; or (i) Mayo stage IV AL amyloidosis, cardiac involvement and 6MWT ≥ 30 meters and ≤ 550 meters The method of claim 1, further comprising one or more of:

2. 10. The method of claim 1, wherein the patient has Mayo stage IV AL amyloidosis.

3. 2. The method of claim 1, wherein the patient has a 6MWT > 150 meters and an EF > 50%.

4. 10. The method of claim 1, wherein the patient has a 6MWT > 30 meters and < 550 meters.

5. The method of claim 4, wherein the patient has an EF>50%.

6. 6. The method of claim 5, wherein the patient has a 6MWT > 150 meters.

7. The method of claim 1 , wherein the patient has a cardiac complication.

8. 10. The method of claim 1, wherein the patient has Mayo stage IV AL amyloidosis and has cardiac complications.

9. 2. The method of claim 1, wherein the patient has Mayo stage IV AL amyloidosis, cardiac involvement and 6MWT > 30 meters and < 550 meters.

10. 1. A method of treating a patient with AL amyloidosis, comprising: (A) Below: i. the patient's Mayo stage of AL amyloidosis; ii. The patient's 6-minute walk distance (6MWT); iii. The patient's ejection fraction (EF); iv. Cardiac complications of the patient determining one or more of: (B) the patient has: (i) having Mayo stage IV AL amyloidosis; (ii) 6MWT ≥ 30 meters and ≤ 550 meters; (iii) having 6MWT ≥ 150 meters and EF > 50% at baseline; (iv) having Mayo stage IV and 6MWT ≥ 30 meters and ≤ 550 meters; (v) having Mayo stage IV and EF>50% at baseline; (vi) Mayo stage IV, 6MWT ≥ 150 meters, and EF > 50% at baseline (vii) having cardiac complications; (viii) Mayo stage IV AL amyloidosis and cardiac complications; or (ix) Mayo stage IV AL amyloidosis, cardiac involvement and 6MWT ≧30 meters and ≦550 meters In the case where the nucleotide sequence has one or more of the following structure: selecting said patient for treatment with (A) an antibody that competes with 2A4 (ATCC Accession No. PTA-9662) or 7D8 (ATCC Accession No. PTA-9468) for binding to human amyloid A peptide or human kappa or lambda light chain immunoglobulin, or competes with 11-1F4 (ATCC Accession No. PTA-105) for binding to kappa light chain immunoglobulin, and (B) daratumumab; (C) administering to the selected patient an effective dose of the antibody; and (D) administering a therapeutically effective dose of daratumumab to the selected patient 5 to 90 minutes after completion of the step of administering the antibody. A method comprising:

11. 11. The method of claim 10, wherein the selected patient has Mayo stage IV amyloidosis.

12. The method of claim 10, wherein the selected patients have a 6MWT > 150 meters and an EF > 50%.

13. 11. The method of claim 10, wherein the selected patient has a 6MWT > 30 meters and < 550 meters.

14. The method of claim 11, wherein the selected patient has an EF>50%.

15. 15. The method of claim 14, wherein the selected patient has a 6MWT > 150 meters.

16. 12. The method of claim 11, wherein the selected patients have a 6MWT > 30 meters and < 550 meters.

17. The method of claim 10 , wherein the selected patient has a cardiac complication.

18. 11. The method of claim 10, wherein the selected patient has Mayo stage IV AL amyloidosis and has cardiac complications.

19. 11. The method of claim 10, wherein the selected patient has Mayo stage IV AL amyloidosis, cardiac involvement and 6MWT > 30 meters and < 550 meters.

20. 1. A method of treating a patient having Mayo stage IV AL amyloidosis and having NYHA class III or NYHA class IV, comprising: administering to the patient a therapeutically effective dose of an antibody that competes with 2A4 (ATCC Accession No. PTA-9662) or 7D8 (ATCC Accession No. PTA-9468) for binding to human amyloid A peptide or human kappa or lambda light chain immunoglobulins, or competes with an amount of 11-1F4 (ATCC Accession No. PTA-105) for binding to kappa light chain immunoglobulins; and administering to the patient a therapeutically effective dose of daratumumab 5 to 90 minutes after completion of the step of administering the antibody, wherein the patient has: (a) 6-minute walking distance (6MWT) ≥ 30 meters and ≤ 550 meters; (b) 6MWT ≥ 150 meters and EF > 50%; (c) Mayo stage IV and EF>50%; (d) Mayo stage IV and 6MWT ≧30 meters and ≦550 meters; (e) Mayo stage IV and 6MWT ≥ 150 meters and EF > 50%; (f) having cardiac complications; (g) Mayo stage IV AL amyloidosis and cardiac complications; or (h) Mayo stage IV AL amyloidosis, cardiac involvement and 6MWT ≧30 meters and ≦550 meters The method of claim 1, further comprising one or more of:

21. 21. The method of claim 20, wherein the patient has a 6MWT > 150 meters and an EF > 50%.

22. 21. The method of claim 20, wherein the patient has a 6MWT > 30 meters and < 550 meters.

23. 23. The method of claim 22, wherein the patient has an EF>50%.

24. 24. The method of claim 23, wherein the patient has a 6MWT > 150 meters.

25. 21. The method of claim 20, wherein the patient has a cardiac complication.

26. 21. The method of claim 20, wherein the patient has Mayo stage IV AL amyloidosis and has cardiac complications.

27. 21. The method of claim 20, wherein the patient has Mayo stage IV AL amyloidosis, cardiac involvement and a 6MWT > 30 meters and < 550 meters.

28. 15. The method of claim 14, wherein the patient's NYHA class is reduced by at least two classes.

29. 30. The method of any one of claims 20 or 28, wherein the patient's NYHA class is assessed after 9 months or more of treatment.

30. 1. A method of reducing mortality or risk of mortality in a patient with Mayo stage IV AL amyloidosis and with NYHA class III or NYHA class IV, comprising: administering to the patient a therapeutically effective dose of an antibody that competes with 2A4 (ATCC Accession No. PTA-9662) or 7D8 (ATCC Accession No. PTA-9468) for binding to human amyloid A peptide or human kappa or lambda light chain immunoglobulins, or competes with an amount of 11-1F4 (ATCC Accession No. PTA-105) for binding to kappa light chain immunoglobulins; and administering to the patient a therapeutically effective dose of daratumumab 5 to 90 minutes after completion of the step of administering the antibody, wherein the patient has: (a) 6-minute walking distance (6MWT) ≥ 30 meters and ≤ 550 meters; (b) 6MWT ≥ 150 meters and EF > 50%; (c) Mayo stage IV and EF>50%; (d) Mayo stage IV and 6MWT ≧30 meters and ≦550 meters; (e) Mayo stage IV and 6MWT ≥ 150 meters and EF > 50%; (f) having cardiac complications; (g) Mayo stage IV AL amyloidosis and cardiac complications; or (h) Mayo stage IV AL amyloidosis, cardiac involvement and 6MWT ≧30 meters and ≦550 meters The method of claim 1, further comprising one or more of:

31. 31. The method of claim 30, wherein the risk of mortality is all-cause mortality.

32. 31. The method of claim 30, wherein the risk of mortality is cardiac mortality.

33. The method of any one of claims 30 to 32, wherein the risk of mortality is assessed after 9 months or more of treatment.

34. The method of any one of claims 30 to 33, wherein the risk of mortality is reduced by at least 15% compared to the risk of mortality in a control population.

35. 31. The method of claim 30, wherein mortality is reduced within 8 months of treatment.

36. 31. The method of claim 30, wherein mortality is reduced within 9 months of treatment.

37. 31. The method of claim 30, wherein mortality is reduced within 10 months of treatment.

38. 31. The method of claim 30, wherein mortality is reduced within 11 months of treatment.

39. 31. The method of claim 30, wherein mortality is reduced within 12 months of treatment.

40. 31. The method of claim 30, wherein the patient has a 6MWT > 150 meters and an EF > 50%.

41. 31. The method of claim 30, wherein the patient has a 6MWT > 30 meters and < 550 meters.

42. 42. The method of claim 41, wherein the patient has an EF>50%.

43. 43. The method of claim 42, wherein the patient has a 6MWT > 150 meters.

44. 31. The method of claim 30, wherein the patient has a cardiac complication.

45. 31. The method of claim 30, wherein the patient has Mayo stage IV AL amyloidosis and has cardiac complications.

46. 31. The method of claim 30, wherein the patient has Mayo stage IV AL amyloidosis, cardiac involvement and 6MWT > 30 meters and < 550 meters.

47. 1. A method for reducing the risk of hospitalization in a patient with Mayo stage IV AL amyloidosis, comprising: administering to the patient a therapeutically effective dose of an antibody that competes with 2A4 (ATCC Accession No. PTA-9662) or 7D8 (ATCC Accession No. PTA-9468) for binding to human amyloid A peptide or human kappa or lambda light chain immunoglobulins, or competes with an amount of 11-1F4 (ATCC Accession No. PTA-105) for binding to kappa light chain immunoglobulins; and administering to the patient a therapeutically effective dose of daratumumab 5 to 90 minutes after completion of the step of administering the antibody, wherein the patient has: (a) 6-minute walking distance (6MWT) ≥ 30 meters and ≤ 550 meters; (b) 6MWT ≥ 150 meters and EF > 50%; (c) Mayo stage IV and EF>50%; (d) Mayo stage IV and 6MWT ≧30 meters and ≦550 meters; (e) Mayo stage IV and 6MWT ≥ 150 meters and EF > 50%; (f) having cardiac complications; (g) Mayo stage IV AL amyloidosis and cardiac complications; or (h) Mayo stage IV AL amyloidosis, cardiac involvement and 6MWT ≧30 meters and ≦550 meters The method of claim 1, further comprising one or more of:

48. 48. The method of claim 47, wherein the patient has a 6MWT > 150 meters and an EF > 50%.

49. 48. The method of claim 47, wherein the patient has a 6MWT > 30 meters and < 550 meters.

50. 50. The method of claim 49, wherein the patient has an EF>50%.

51. 51. The method of claim 50, wherein the patient has a 6MWT > 150 meters.

52. 48. The method of claim 47, wherein the patient has a cardiac complication.

53. 48. The method of claim 47, wherein the patient has Mayo stage IV AL amyloidosis and has cardiac complications.

54. 48. The method of claim 47, wherein the patient has Mayo stage IV AL amyloidosis, cardiac involvement and 6MWT > 30 meters and < 550 meters.

55. 48. The method of claim 47, wherein the risk of hospitalization in the patient is reduced by at least 20% compared to the risk of hospitalization in a control population.

56. 1. A method for increasing the number of days alive out of hospital (DAOH) in a patient with Mayo stage IV amyloidosis, comprising: administering to the patient a therapeutically effective dose of an antibody that competes with 2A4 (ATCC Accession No. PTA-9662) or 7D8 (ATCC Accession No. PTA-9468) for binding to human amyloid A peptide or human kappa or lambda light chain immunoglobulins, or competes with an amount of 11-1F4 (ATCC Accession No. PTA-105) for binding to kappa light chain immunoglobulins; and administering to the patient a therapeutically effective dose of daratumumab 5 to 90 minutes after completion of the step of administering the antibody, wherein the patient has: (a) 6-minute walking distance (6MWT) ≥ 30 meters and ≤ 550 meters; (b) 6MWT ≥ 150 meters and EF > 50%; (c) Mayo stage IV and EF>50%; (d) Mayo stage IV and 6MWT ≧30 meters and ≦550 meters; (e) Mayo stage IV and 6MWT ≥ 150 meters and EF > 50%; (f) having cardiac complications; (g) Mayo stage IV AL amyloidosis and cardiac complications; or (h) Mayo stage IV AL amyloidosis, cardiac involvement and 6MWT ≧30 meters and ≦550 meters The method of claim 1, further comprising one or more of:

57. 57. The method of claim 56, wherein the number of DAOH is increased for at least 20 days after one month of treatment compared to a control population.

58. 58. The method of claim 56 or 57, wherein the number of DAOH is increased for at least 100 days after 6 months of treatment compared to DAOH in a control population.

59. 59. The method of any one of claims 56-58, wherein the number of DAOH is increased by at least 300 after 12 months of treatment compared to DAOH in a control population.

60. 60. The method of any one of claims 56-59, wherein the number of DAOH is increased by at least 600 after 24 months of treatment compared to DAOH in a control population.

61. 61. The method of any one of claims 56-60, wherein the number of DAOH is increased by at least 900 after 48 months of treatment compared to DAOH in a control population.

62. 57. The method of claim 56, wherein the patient has a 6MWT > 150 meters and an EF > 50%.

63. 57. The method of claim 56, wherein the patient has a 6MWT > 30 meters and < 550 meters.

64. 64. The method of claim 63, wherein the patient has an EF>50%.

65. 65. The method of claim 64, wherein the patient has a 6MWT > 150 meters.

66. 57. The method of claim 56, wherein the patient has a cardiac complication.

67. 57. The method of claim 56, wherein the patient has Mayo stage IV AL amyloidosis and has cardiac complications.

68. 57. The method of claim 56, wherein the patient has Mayo stage IV AL amyloidosis, cardiac involvement and a 6MWT > 30 meters and < 550 meters.

69. 1. A method of reducing NTproBNP levels in a patient with Mayo stage IV AL amyloidosis, comprising: administering to the patient a therapeutically effective dose of an antibody that competes with 2A4 (ATCC Accession No. PTA-9662) or 7D8 (ATCC Accession No. PTA-9468) for binding to human amyloid A peptide or human kappa or lambda light chain immunoglobulins, or competes with an amount of 11-1F4 (ATCC Accession No. PTA-105) for binding to kappa light chain immunoglobulins; and administering to the patient a therapeutically effective dose of daratumumab 5 to 90 minutes after completion of the step of administering the antibody, wherein the patient has: (a) 6-minute walking distance (6MWT) ≥ 30 meters and ≤ 550 meters; (b) 6MWT ≥ 150 meters and EF > 50%; (c) Mayo stage IV and EF>50%; (d) Mayo stage IV and 6MWT ≧30 meters and ≦550 meters; (e) Mayo stage IV and 6MWT ≥ 150 meters and EF > 50%; (f) having cardiac complications; (g) Mayo stage IV AL amyloidosis and cardiac complications; or (h) Mayo stage IV AL amyloidosis, cardiac involvement and 6MWT ≧30 meters and ≦550 meters The method comprising:

70. 70. The method of claim 69, wherein the NTproBNP level is reduced by at least 31% from baseline after 3 months of treatment.

71. 71. The method of claim 69 or 70, wherein the NTproBNP level is reduced by at least 45% from baseline after 3 months of treatment.

72. 72. The method of any one of claims 69-71, wherein the NTproBNP levels are reduced by at least 60% from baseline after 3 months of treatment.

73. 73. The method of any one of claims 69-72, wherein the NTproBNP level is reduced by at least 60% from baseline to a nadir >400 pg / ml after 3 months of treatment.

74. 74. The method of any one of claims 69-73, wherein the NTproBNP level is reduced to a nadir <400 pg / ml after 3 months of treatment.

75. 75. The method of any one of claims 69-74, wherein the NTproBNP level is reduced by at least 45% from baseline after 6 months of treatment.

76. 76. The method of any one of claims 69-75, wherein the NTproBNP level is reduced by at least 60% from baseline after 6 months of treatment.

77. 77. The method of any one of claims 69-76, wherein the NTproBNP level is reduced by at least 60% from baseline to a nadir >400 pg / ml after 6 months of treatment.

78. 77. The method of any one of claims 69-76, wherein the NTproBNP level is reduced to a nadir <400 pg / ml after 3 months of treatment.

79. 70. The method of claim 69, wherein the patient has a 6MWT > 150 meters and an EF > 50%.

80. 70. The method of claim 69, wherein the patient has a 6MWT > 30 meters and < 550 meters.

81. 81. The method of claim 80, wherein the patient has an EF>50%.

82. 82. The method of claim 81, wherein the patient has a 6MWT > 150 meters.

83. 70. The method of claim 69, wherein the patient has a cardiac complication.

84. 70. The method of claim 69, wherein the patient has Mayo stage IV AL amyloidosis and has cardiac complications.

85. 70. The method of claim 69, wherein the patient has Mayo stage IV AL amyloidosis, cardiac involvement and 6MWT > 30 meters and < 550 meters.

86. 1. A method of improving cardiac response rate in patients with Mayo stage IV AL amyloidosis, comprising: administering a therapeutically effective amount of an antibody that competes with 2A4 (ATCC Accession No. PTA-9662) or 7D8 (ATCC Accession No. PTA-9468) for binding to human amyloid A peptide or human kappa or lambda light chain immunoglobulins, or competes with an amount of 11-1F4 (ATCC Accession No. PTA-105) for binding to kappa light chain immunoglobulins; and administering to the patient a therapeutically effective dose of daratumumab 5 to 90 minutes after completion of the step of administering the antibody, wherein the patient has: (a) 6-minute walking distance (6MWT) ≥ 30 meters and ≤ 550 meters; (b) 6MWT ≥ 150 meters and EF > 50%; (c) Mayo stage IV and EF>50%; (d) Mayo stage IV and 6MWT ≧30 meters and ≦550 meters; (e) Mayo stage IV and 6MWT ≥ 150 meters and EF > 50%; (f) having cardiac complications; (g) Mayo stage IV AL amyloidosis and cardiac complications; or (h) Mayo stage IV AL amyloidosis, cardiac involvement and 6MWT ≧30 meters and ≦550 meters The method comprising:

87. 87. The method of claim 86, wherein the cardiac response rate is increased by at least 30% after 6 months of treatment compared to baseline.

88. 88. The method of any of claims 86 or 87, wherein the cardiac response rate is increased by at least 50% after 12 months of treatment compared to baseline.

89. 89. The method of any one of claims 86-88, wherein the cardiac response rate is increased by at least 75% after 12 months of treatment compared to baseline.

90. 87. The method of claim 86, wherein the patient has a 6MWT > 150 meters and an EF > 50%.

91. 87. The method of claim 86, wherein the patient has a 6MWT > 30 meters and < 550 meters.

92. 92. The method of claim 91, wherein the patient has an EF>50%.

93. 93. The method of claim 92, wherein the patient has a 6MWT > 150 meters.

94. 87. The method of claim 86, wherein the patient has a cardiac complication.

95. 87. The method of claim 86, wherein the patient has Mayo stage IV AL amyloidosis and has cardiac complications.

96. 87. The method of claim 86, wherein the patient has Mayo stage IV AL amyloidosis, cardiac involvement and 6MWT > 30 meters and < 550 meters.

97. 1. A method of improving 6-minute walk distance (6MWT) in a patient with Mayo stage IV AL amyloidosis, comprising: administering a therapeutically effective dose of an antibody that competes with 2A4 (ATCC Accession No. PTA-9662) or 7D8 (ATCC Accession No. PTA-9468) for binding to human amyloid A peptide or human kappa or lambda light chain immunoglobulins, or competes with an amount of 11-1F4 (ATCC Accession No. PTA-105) for binding to kappa light chain immunoglobulins; and administering to the patient a therapeutically effective dose of daratumumab 5 to 90 minutes after completion of the step of administering the antibody; (a) 6-minute walking distance (6MWT) ≥ 30 meters and ≤ 550 meters; (b) 6MWT ≥ 150 meters and EF > 50%; (c) Mayo stage IV and EF>50%; (d) Mayo stage IV and 6MWT ≧30 meters and ≦550 meters; (e) Mayo stage IV and 6MWT ≥ 150 meters and EF > 50%; (f) having cardiac complications; (g) Mayo stage IV AL amyloidosis and cardiac complications; or (h) Mayo stage IV AL amyloidosis, with cardiac involvement and 6MWT ≧30 meters and ≦550 meters; method.

98. 98. The method of claim 97, wherein the 6MWT achieved is at least 300 meters.

99. 99. The method of claim 97 or 98, wherein the 6MWT achieved is at least 300 meters after 3 months of treatment.

100. 99. The method of claim 97 or 98, wherein the 6MWT achieved is at least 300 meters after 6 months of treatment.

101. 99. The method of claim 97 or 98, wherein the 6MWT achieved is at least 300 meters after 9 months of treatment.

102. 99. The method of claim 97 or 98, wherein the 6MWT achieved is at least 300 meters after 12 months of treatment.

103. 99. The method of claim 97 or 98, wherein the 6MWT achieved is at least 300 meters after 15 months of treatment.

104. 99. The method of claim 97 or 98, wherein the 6MWT achieved is at least 300 meters after 18 months of treatment.

105. 105. The method of any one of claims 97 to 104, wherein the 6MWT improves by at least 33 meters compared to a baseline.

106. 100. The method of any one of claims 97-99, wherein the 6MWT improves by at least 33 meters after 3 months of treatment compared to baseline.

107. 101. The method of any one of claims 97-100, wherein the 6MWT improves by at least 33 meters after 6 months of treatment compared to baseline.

108. 102. The method of any one of claims 97-101, wherein the 6MWT improves by at least 33 meters after 9 months of treatment compared to baseline.

109. 103. The method of any one of claims 97-102, wherein the 6MWT improves by at least 33 meters after 12 months of treatment compared to baseline.

110. 104. The method of any one of claims 97-103, wherein the 6MWT improves by at least 33 meters after 15 months of treatment.

111. 105. The method of any one of claims 97-104, wherein the 6MWT improves by at least 33 meters after 18 months of treatment.

112. 106. The method of any one of claims 97-105, wherein the 6MWT achieved is at least 300 meters after 18 months of treatment.

113. 113. The method of any one of claims 97-112, wherein the 6MWT improves by at least 33 meters after 18 months of treatment compared to baseline.

114. 98. The method of claim 97, wherein the patient has a 6MWT > 150 meters and an EF > 50%.

115. 98. The method of claim 97, wherein the patient has a 6MWT > 30 meters and < 550 meters.

116. The method of claim 115, wherein the patient has an EF>50%.

117. 117. The method of claim 116, wherein the patient has a 6MWT > 150 meters.

118. 98. The method of claim 97, wherein the patient has a cardiac complication.

119. 98. The method of claim 97, wherein the patient has Mayo stage IV AL amyloidosis and has cardiac complications.

120. 98. The method of claim 97, wherein the patient has Mayo stage IV AL amyloidosis, cardiac involvement and 6MWT > 30 meters and < 550 meters.

121. 1. A method of increasing the Kansas City Cardiomyopathy Questionnaire (KCCQ) score in a patient with Mayo stage IV AL amyloidosis, comprising: administering a therapeutically effective dose of an antibody that competes with 2A4 (ATCC Accession No. PTA-9662) or 7D8 (ATCC Accession No. PTA-9468) for binding to human amyloid A peptide or human kappa or lambda light chain immunoglobulins, or competes with an amount of 11-1F4 (ATCC Accession No. PTA-105) for binding to kappa light chain immunoglobulins; and administering to the patient a therapeutically effective dose of daratumumab 5 to 90 minutes after completion of the step of administering the antibody, wherein the patient has: (a) 6-minute walking distance (6MWT) ≥ 30 meters and ≤ 550 meters; (b) 6MWT ≥ 150 meters and EF > 50%; (c) Mayo stage IV and EF>50%; (d) Mayo stage IV and 6MWT ≧30 meters and ≦550 meters; (e) Mayo stage IV and 6MWT ≥ 150 meters and EF > 50%; (f) having cardiac complications; (g) Mayo stage IV AL amyloidosis and cardiac complications; or (h) Mayo stage IV AL amyloidosis, cardiac involvement and 6MWT ≧30 meters and ≦550 meters The method of claim 1, further comprising one or more of:

122. 122. The method of claim 121, wherein the KCCQ score is increased by at least 5 after 3 months of treatment compared to baseline.

123. 123. The method of claim 121 or 122, wherein the KCCQ score is increased by at least 10 after 3 months of treatment compared to baseline.

124. The method of any one of claims 121-123, wherein the KCCQ score is increased by at least 15 after 3 months of treatment compared to baseline.

125. 125. The method of any one of claims 121-124, wherein the KCCQ score improves by at least 20 after 3 months of treatment compared to baseline.

126. The method of any one of claims 121 to 125, wherein the KCCQ score improves by at least 5 after 12 months of treatment compared to baseline.

127. The method of any one of claims 121-126, wherein the KCCQ score improves by at least 10 after 12 months of treatment compared to baseline.

128. The method of any one of claims 121-127, wherein the KCCQ score improves by at least 15 after 12 months of treatment compared to baseline.

129. The method of any one of claims 121-128, wherein the KCCQ score improves by at least 20 after 12 months of treatment compared to baseline.

130. 122. The method of claim 121, wherein the patient has a 6MWT > 150 meters and an EF > 50%.

131. 122. The method of claim 121, wherein the patient has a 6MWT > 30 meters and < 550 meters.

132. The method of claim 131, wherein the patient has an EF>50%.

133. 133. The method of claim 132, wherein the patient has a 6MWT > 150 meters.

134. The method of claim 121, wherein the patient has a cardiac complication.

135. 122. The method of claim 121, wherein the patient has Mayo stage IV AL amyloidosis and has cardiac complications.

136. 122. The method of claim 121, wherein the patient has Mayo stage IV AL amyloidosis, cardiac involvement and 6MWT > 30 meters and < 550 meters.

137. 1. A method for increasing major organ progression-free survival in patients with Mayo class IV AL amyloidosis, comprising: administering to the patient a therapeutically effective dose of an antibody that competes with 2A4 (ATCC Accession No. PTA-9662) or 7D8 (ATCC Accession No. PTA-9468) for binding to human amyloid A peptide or human kappa or lambda light chain immunoglobulins, or competes with an amount of 11-1F4 (ATCC Accession No. PTA-105) for binding to kappa light chain immunoglobulins; and administering to the patient a therapeutically effective dose of daratumumab 5 to 90 minutes after completion of the step of administering the antibody, wherein the patient has: (a) 6-minute walking distance (6MWT) ≥ 30 meters and ≤ 550 meters; (b) 6MWT ≥ 150 meters and EF > 50%; (c) Mayo stage IV and EF>50%; (d) Mayo stage IV and 6MWT ≧30 meters and ≦550 meters; (e) Mayo stage IV and 6MWT ≥ 150 meters and EF > 50%; (f) having cardiac complications; (g) Mayo stage IV AL amyloidosis and cardiac complications; or (h) Mayo stage IV AL amyloidosis, cardiac involvement and 6MWT ≧30 meters and ≦550 meters The method of claim 1, further comprising one or more of:

138. 138. The method of claim 137, wherein the NTproBNP level is reduced by at least 31% from baseline after 3 months of treatment.

139. 139. The method of claim 137 or 138, wherein the NTproBNP level is reduced by at least 45% from baseline after 3 months of treatment.

140. 140. The method of any one of claims 137-139, wherein the NTproBNP levels are reduced by at least 60% from baseline after 3 months of treatment.

141. The method of any one of claims 137-140, wherein the NTproBNP level is reduced by at least 60% from baseline to a nadir >400 pg / ml after 3 months of treatment.

142. 142. The method of any one of claims 137-141, wherein the NTproBNP level is reduced to a nadir <400 pg / ml after 3 months of treatment.

143. The method of any one of claims 137-142, wherein the NTproBNP level is reduced by at least 45% from baseline after 6 months of treatment.

144. The method of any one of claims 137-143, wherein the NTproBNP levels are reduced by at least 60% from baseline after 6 months of treatment.

145. The method of any one of claims 137-144, wherein the NTproBNP level is reduced by at least 60% from baseline to a nadir >400 pg / ml after 6 months of treatment.

146. 146. The method of any one of claims 137-145, wherein the NTproBNP level is reduced to a nadir <400 pg / ml after 3 months of treatment.

147. 138. The method of claim 137, wherein the patient has a 6MWT≧150 meters and an EF>50%.

148. 138. The method of claim 137, wherein the patient has a 6MWT > 30 meters and < 550 meters.

149. The method of claim 148, wherein the patient has an EF>50%.

150. 150. The method of claim 149, wherein the patient has a 6MWT > 150 meters.

151. The method of claim 137, wherein the patient has a cardiac complication.

152. 138. The method of claim 137, wherein the patient has Mayo stage IV AL amyloidosis and has cardiac complications.

153. 138. The method of claim 137, wherein the patient has Mayo stage IV AL amyloidosis, cardiac involvement and 6MWT > 30 meters and < 550 meters.

154. 1. A method of treating a patient with AL amyloidosis, comprising: (a) determining that the patient has a 6 minute walk distance (6MWT) > 30 meters and < 550 meters or a 6MWT > 150 meters and / or an ejection fraction (EF) > 50%; (b) selecting said patient for treatment with an antibody that competes with 2A4 (ATCC Accession No. PTA-9662) or 7D8 (ATCC Accession No. PTA-9468) for binding to human amyloid A peptide or human kappa or lambda light chain immunoglobulin, or competes with 11-1F4 (ATCC Accession No. PTA-105) for binding to kappa light chain immunoglobulin, and daratumumab; (c) administering to the selected patient an effective dose of the antibody; and (d) administering to the selected patient a therapeutically effective amount of daratumumab 5 to 90 minutes after completion of the step of administering the antibody, wherein the patient has: (a) Mayo stage IV AL amyloidosis; (b) 6-minute walking distance (6MWT) ≥ 30 meters and ≤ 550 meters; (c) 6MWT ≥ 150 meters and EF > 50%; (d) Mayo stage IV and EF>50%; (e) Mayo stage IV and 6MWT ≧30 meters and ≦550 meters; (f) Mayo stage IV and 6MWT ≥ 150 meters and EF > 50%; (g) having cardiac complications; (h) Mayo stage IV AL amyloidosis and cardiac complications; or (i) Mayo stage IV AL amyloidosis, cardiac involvement and 6MWT ≥ 30 meters and ≤ 550 meters [0046] The method further comprises the steps of: A method comprising:

155. 155. The method of claim 154, wherein the patient has Mayo stage IV AL amyloidosis.

156. 155. The method of claim 154, wherein the patient has a 6MWT≧150 meters and an EF>50%.

157. 155. The method of claim 154, wherein the patient has a 6MWT > 30 meters and < 550 meters.

158. The method of claim 157, wherein the patient has an EF>50%.

159. 159. The method of claim 158, wherein the patient has a 6MWT > 150 meters.

160. The method of claim 154, wherein the patient has a cardiac complication.

161. 155. The method of claim 154, wherein the patient has Mayo stage IV AL amyloidosis and has cardiac complications.

162. 155. The method of claim 154, wherein the patient has Mayo stage IV AL amyloidosis, cardiac involvement and 6MWT > 30 meters and < 550 meters.

163. 1. A method of treating a patient with AL amyloidosis having a documented 6 minute walk distance (6MWT) of > 30 meters and < 550 meters or a 6MWT greater than or equal to 150 meters and / or an ejection fraction (EF) > 50%, comprising: administering to the patient an effective dose of an antibody which competes with 2A4 (ATCC Accession No. PTA-9662) or 7D8 (ATCC Accession No. PTA-9468) for binding to human amyloid A peptide or human kappa or lambda light chain immunoglobulins, or which competes with 11-1F4 (ATCC Accession No. PTA-105) for binding to kappa light chain immunoglobulins; and administering to the patient a therapeutically effective amount of daratumumab 5 to 90 minutes after completion of the step of administering the antibody, wherein the patient has: (a) Mayo stage IV AL amyloidosis; (b) 6-minute walking distance (6MWT) ≥ 30 meters and ≤ 550 meters; (c) 6MWT ≥ 150 meters and EF > 50%; (d) Mayo stage IV and EF>50%; (e) Mayo stage IV and 6MWT ≧30 meters and ≦550 meters; (f) Mayo stage IV and 6MWT ≥ 150 meters and EF > 50%; (g) having cardiac complications; (h) Mayo stage IV AL amyloidosis and cardiac complications; or (i) Mayo stage IV AL amyloidosis, cardiac involvement and 6MWT ≥ 30 meters and ≤ 550 meters [0046] The method further comprises the steps of: A method comprising:

164. 164. The method of claim 163, wherein the patient has Mayo stage IV AL amyloidosis.

165. 164. The method of claim 163, wherein the patient has a 6MWT≧150 meters and an EF>50%.

166. 164. The method of claim 163, wherein the patient has a 6MWT > 30 meters and < 550 meters.

167. The method of claim 166, wherein the patient has an EF>50%.

168. 168. The method of claim 167, wherein the patient has a 6MWT > 150 meters.

169. The method of claim 163, wherein the patient has a cardiac complication.

170. 164. The method of claim 163, wherein the patient has Mayo stage IV AL amyloidosis and has cardiac complications.

171. The method of claim 163, wherein the patient has Mayo stage IV AL amyloidosis, cardiac involvement and 6MWT > 30 meters and < 550 meters.

172. 1. A method for reducing the risk of mortality in a patient with AL amyloidosis by at least 45%, comprising: administering to said patient an effective dose of an antibody which competes with 2A4 (ATCC Accession No. PTA-9662) or 7D8 (ATCC Accession No. PTA-9468) for binding to human amyloid A peptide or human kappa or lambda light chain immunoglobulins, or which competes with 11-1F4 (ATCC Accession No. PTA-105), 6MWT for binding to kappa light chain immunoglobulins; administering to the patient a therapeutically effective amount of daratumumab 5 to 90 minutes after completion of the step of administering the antibody, wherein the patient has: (a) Mayo stage IV AL amyloidosis; (b) 6-minute walking distance (6MWT) ≥ 30 meters and ≤ 550 meters; (c) 6MWT ≥ 150 meters and EF > 50%; (d) Mayo stage IV and EF>50%; (e) Mayo stage IV and 6MWT ≧30 meters and ≦550 meters; (f) Mayo stage IV and 6MWT ≥ 150 meters and EF > 50%; (g) having cardiac complications; (h) Mayo stage IV AL amyloidosis and cardiac complications; or (i) Mayo stage IV AL amyloidosis, cardiac involvement and 6MWT ≥ 30 meters and ≤ 550 meters [0046] The method further comprises the steps of: A method comprising:

173. 173. The method of claim 172, wherein the risk of mortality is risk of all-cause mortality.

174. 174. The method of claim 173, wherein the risk of all cause mortality is reduced by at least about 48.9%.

175. The method of claim 17388, wherein the risk of all cause mortality is reduced by at least about 50%.

176. 174. The method of claim 173, wherein the risk of all cause mortality is reduced by at least about 50.2%.

177. 174. The method of claim 173, wherein the risk of all-cause mortality is reduced by at least about 60%.

178. 174. The method of claim 173, wherein the risk of all-cause mortality is reduced by at least about 70%.

179. 174. The method of claim 173, wherein the risk of all cause mortality is reduced by at least about 79.9%.

180. 174. The method of claim 173, wherein the risk of all cause mortality is reduced by at least about 81.5%.

181. 173. The method of claim 172, wherein the risk of mortality is a risk of cardiac mortality.

182. 182. The method of claim 181, wherein the risk of cardiac mortality is reduced by at least about 75%.

183. 183. The method of claim 182, wherein said risk of cardiac mortality is reduced by at least about 62.2%.

184. 173. The method of claim 172, wherein the patient has Mayo stage IV AL amyloidosis.

185. 173. The method of claim 172, wherein the patient has a 6MWT≧150 meters and an EF>50%.

186. 173. The method of claim 172, wherein the patient has a 6MWT > 30 meters and < 550 meters.

187. The method of claim 186, wherein the patient has an EF>50%.

188. 188. The method of claim 187, wherein the patient has a 6MWT > 150 meters.

189. The method of claim 172, wherein the patient has a cardiac complication.

190. 173. The method of claim 172, wherein the patient has Mayo stage IV AL amyloidosis and has cardiac complications.

191. 173. The method of claim 172, wherein the patient has Mayo stage IV AL amyloidosis, cardiac involvement and 6MWT > 30 meters and < 550 meters.

192. 1. A method of reducing global longitudinal strain (GLS) in a patient with AL amyloidosis, comprising: administering to said patient an effective dose of an antibody which competes with 2A4 (ATCC Accession No. PTA-9662) or 7D8 (ATCC Accession No. PTA-9468) for binding to human amyloid A peptide or human kappa or lambda light chain immunoglobulins, or which competes with 11-1F4 (ATCC Accession No. PTA-105), 6MWT for binding to kappa light chain immunoglobulins; administering to the patient a therapeutically effective amount of daratumumab 5 to 90 minutes after completion of the step of administering the antibody, wherein the patient has: (a) Mayo stage IV AL amyloidosis; (b) 6-minute walking distance (6MWT) ≥ 30 meters and ≤ 550 meters; (c) 6MWT ≥ 150 meters and EF > 50%; (d) Mayo stage IV and EF>50%; (e) Mayo stage IV and 6MWT ≧30 meters and ≦550 meters; (f) Mayo stage IV and 6MWT ≥ 150 meters and EF > 50%; (g) having cardiac complications; (h) Mayo stage IV AL amyloidosis and cardiac complications; or (i) Mayo stage IV AL amyloidosis, cardiac involvement and 6MWT ≥ 30 meters and ≤ 550 meters [0046] The method further comprises the steps of: A method comprising:

193. 193. The method of claim 192, wherein the administering step results in a reduction in GLS in the patient of about 0.1% to about 10%.

194. 194. The method of claim 193, wherein the administering step results in a reduction of GLS in the human subject of about 0.5% to about 10%.

195. 194. The method of claim 193, wherein the administering step results in a reduction of GLS in the human subject of about 1% to about 10%.

196. 194. The method of claim 193, wherein the administering step results in a reduction of GLS in the human subject of at least about 0.5%.

197. 194. The method of claim 193, wherein the administering step results in a reduction of GLS in the human subject of at least about 1.0%.

198. 194. The method of claim 193, wherein the administering step results in a reduction of GLS in the human subject of at least about 2.0%.

199. 194. The method of claim 193, wherein the administering step results in a reduction of GLS in the human subject of at least about 10%.

200. 193. The method of claim 192, wherein the patient has Mayo stage IV AL amyloidosis.

201. 193. The method of claim 192, wherein the patient has a 6MWT≧150 meters and an EF>50%.

202. 193. The method of claim 192, wherein the patient has a 6MWT > 30 meters and < 550 meters.

203. The method of claim 202, wherein the patient has an EF>50%.

204. 204. The method of claim 203, wherein the patient has a 6MWT > 150 meters.

205. The method of claim 192, wherein the patient has a cardiac complication.

206. 193. The method of claim 192, wherein the patient has Mayo stage IV AL amyloidosis and has cardiac complications.

207. 193. The method of claim 192, wherein the patient has Mayo stage IV AL amyloidosis, cardiac involvement and 6MWT > 30 meters and < 550 meters.

208. 1. A method of improving SF-36v2 physical component summary (PCS) score in a patient with AL amyloidosis, comprising: administering to the patient an effective dose of an antibody which competes with 2A4 (ATCC Accession No. PTA-9662) or 7D8 (ATCC Accession No. PTA-9468) for binding to human amyloid A peptide or human kappa or lambda light chain immunoglobulins, or which competes with 11-1F4 (ATCC Accession No. PTA-105) for binding to kappa light chain immunoglobulins; and administering to the patient a therapeutically effective amount of daratumumab 5 to 90 minutes after completion of the step of administering the antibody, wherein the SF-36v2 score is determined at least one month after treatment and the patient has one of the following: (a) Mayo stage IV AL amyloidosis; (b) 6-minute walking distance (6MWT) ≥ 30 meters and ≤ 550 meters; (c) 6MWT ≥ 150 meters and EF > 50%; (d) Mayo stage IV and EF>50%; (e) Mayo stage IV and 6MWT ≧30 meters and ≦550 meters; (f) Mayo stage IV and 6MWT ≥ 150 meters and EF > 50%; (g) having cardiac complications; (h) Mayo stage IV AL amyloidosis and cardiac complications; or (i) Mayo stage IV AL amyloidosis, cardiac involvement and 6MWT ≥ 30 meters and ≤ 550 meters [0046] The method further comprises the steps of: A method comprising:

209. The method of claim 208, wherein the duration of treatment is effective to achieve or maintain at least about a 5 point increase from baseline in SF-36v2.

210. The method of claim 208 or 209, wherein the SF-36v2 PCS score is determined after 2 months of treatment.

211. The method of claim 208 or 209, wherein the SF-36v2 PCS score is determined after 3 months of treatment.

212. The method of claim 208 or 209, wherein the SF-36v2 PCS score is determined after 6 months of treatment.

213. The method of claim 208 or 209, wherein the SF-36v2 PCS score is determined after 9 months of treatment.

214. The method of claim 208 or 209, wherein the SF-36v2 PCS score is determined after 12 months of treatment.

215. The method of claim 208, wherein the patient has Mayo stage IV AL amyloidosis.

216. The method of claim 208, wherein the patient has a 6MWT≧150 meters and an EF>50%.

217. 209. The method of claim 208, wherein the patient has a 6MWT > 30 meters and < 550 meters.

218. The method of claim 217, wherein the patient has an EF>50%.

219. The method of claim 218, wherein the patient has a 6MWT≧150 meters.

220. The method of claim 208, wherein the patient has a cardiac complication.

221. The method of claim 208, wherein the patient has Mayo stage IV AL amyloidosis and has cardiac complications.

222. The method of claim 208, wherein the patient has Mayo stage IV AL amyloidosis, cardiac involvement and 6MWT > 30 meters and < 550 meters.

223. 1. A method of reducing mortality or risk of mortality in a patient with Mayo stage IV AL amyloidosis, comprising: administering to said patient an effective dose of an antibody which competes with 2A4 (ATCC Accession No. PTA-9662) or 7D8 (ATCC Accession No. PTA-9468) for binding to human amyloid A peptide or human kappa or lambda light chain immunoglobulins, or which competes with 11-1F4 (ATCC Accession No. PTA-105) for binding to kappa light chain immunoglobulins; administering a therapeutically effective dose of daratumumab to said patient 5 to 90 minutes after completion of the step of administering said antibody. A method comprising:

224. 224. The method of claim 223, wherein the risk of mortality is all-cause mortality.

225. 224. The method of claim 223, wherein the risk of mortality is cardiac mortality.

226. The method of any one of claims 223 to 225, wherein the risk of mortality is reduced after one month of treatment.

227. The method of any one of claims 223 to 225, wherein said risk of mortality is reduced after 2 months of treatment.

228. The method of any one of claims 223 to 225, wherein the risk of mortality is reduced after 3 months of treatment.

229. The method of any one of claims 223 to 225, wherein said risk of mortality is reduced after 4 months of treatment.

230. The method of any one of claims 223 to 225, wherein the risk of mortality is reduced after 5 months of treatment.

231. The method of any one of claims 223 to 225, wherein the risk of mortality is reduced after 6 months of treatment.

232. The method of any one of claims 223 to 225, wherein said risk of mortality is reduced after 7 months of treatment.

233. The method of any one of claims 223 to 225, wherein said risk of mortality is reduced after 8 months of treatment.

234. The method of any one of claims 223 to 225, wherein the risk of mortality is reduced after 9 months of treatment.

235. The method of any one of claims 223-225, wherein said risk of mortality is reduced after 10 months of treatment.

236. The method of any one of claims 223 to 225, wherein the risk of mortality is reduced after 11 months of treatment.

237. The method of claims 223-225, wherein said risk of mortality is reduced after 12 months of treatment.

238. The method of any one of claims 223 to 225, wherein the risk of mortality is reduced by at least 15% compared to the risk of mortality in a control population.

239. The method of claim 223, wherein the patient has a 6MWT≧150 meters and an EF>50%.

240. 224. The method of claim 223, wherein the patient has a 6MWT > 30 meters and < 550 meters.

241. The method of claim 240, wherein the patient has EF>50%.

242. 242. The method of claim 241, wherein the patient has a 6MWT > 150 meters.

243. The method of claim 223, wherein the patient has a cardiac complication.

244. 224. The method of claim 223, wherein the patient has Mayo stage IV AL amyloidosis and has cardiac complications.

245. The method of claim 223, wherein the patient has Mayo stage IV AL amyloidosis, cardiac involvement and 6MWT > 30 meters and < 550 meters.

246. 1. A method of reducing global longitudinal strain (GLS) in a patient with Mayo stage IV AL amyloidosis, comprising administering to the patient an effective dosage of an antibody that competes with 2A4 (ATCC Accession No. PTA-9662) or 7D8 (ATCC Accession No. PTA-9468) for binding to human amyloid A peptide or human kappa or lambda light chain immunoglobulins, or that competes with 11-1F4 (ATCC Accession No. PTA-105) for binding to kappa light chain immunoglobulins.

247. The method of claim 246, wherein the administering step results in a reduction in GLS in the patient of about 0.1% to about 10%.

248. The method of claim 247, wherein the administering step results in a reduction in GLS in the patient of about 0.5% to about 10%.

249. The method of claim 247, wherein the administering step results in a reduction in GLS in the patient of about 1% to about 10%.

250. 248. The method of claim 247, wherein the administering step results in a reduction in GLS in the patient of at least about 0.5%.

251. 248. The method of claim 247, wherein the administering step results in a reduction in GLS in the patient of at least about 1.0%.

252. 248. The method of claim 247, wherein the administering step results in a reduction in GLS in the patient of at least about 2.0%.

253. 248. The method of claim 247, wherein the administering step results in a reduction in GLS of at least about 10% in the patient.

254. The method of claim 246, wherein the patient has a 6MWT≧150 meters and an EF>50%.

255. 247. The method of claim 246, wherein the patient has a 6MWT > 30 meters and < 550 meters.

256. The method of claim 246, wherein the patient has EF>50%.

257. The method of claim 246, wherein the patient has a 6MWT≧150 meters.

258. The method of claim 246, wherein the patient has a cardiac complication.

259. The method of claim 246, wherein the patient has Mayo stage IV AL amyloidosis and has cardiac complications.

260. The method of claim 246, wherein the patient has Mayo stage IV AL amyloidosis, cardiac involvement and 6MWT > 30 meters and < 550 meters.

261. 1. A method of reducing longitudinal global strain (GLS) in a patient with Mayo stage IV AL amyloidosis, comprising: administering to the patient an effective dose of an antibody which competes with 2A4 (ATCC Accession No. PTA-9662) or 7D8 (ATCC Accession No. PTA-9468) for binding to human amyloid A peptide or human kappa or lambda light chain immunoglobulins, or which competes with 11-1F4 (ATCC Accession No. PTA-105) for binding to kappa light chain immunoglobulins; and administering a therapeutically effective dose of daratumumab to said patient 5 to 90 minutes after completion of the step of administering said antibody. A method comprising:

262. 262. The method of claim 261, wherein the administering step results in a reduction in GLS in the patient of about 0.1% to about 10%.

263. 263. The method of claim 262, wherein the administering step results in a reduction in GLS in the patient of about 0.5% to about 10%.

264. 263. The method of claim 262, wherein the administering step results in a reduction in GLS in the patient of about 1% to about 10%.

265. 263. The method of claim 262, wherein the administering step results in a reduction in GLS in the patient of at least about 0.5%.

266. 263. The method of claim 262, wherein the administering step results in a reduction in GLS in the patient of at least about 1.0%.

267. 263. The method of claim 262, wherein the administering step results in a reduction in GLS in the patient of at least about 2.0%.

268. 263. The method of claim 262, wherein the administering step results in a reduction in GLS in the patient of at least about 10%.

269. The method of claim 261, wherein the patient has a 6MWT≧150 meters and an EF>50%.

270. 262. The method of claim 261, wherein the patient has a 6MWT > 30 meters and < 550 meters.

271. The method of claim 261, wherein the patient has EF>50%.

272. The method of claim 261, wherein the patient has a 6MWT≧150 meters.

273. The method of claim 261, wherein the patient has a cardiac complication.

274. The method of claim 261, wherein the patient has Mayo stage IV AL amyloidosis and has cardiac complications.

275. The method of claim 261, wherein the selected patient has Mayo stage IV AL amyloidosis, cardiac involvement and 6MWT > 30 meters and < 550 meters.

276. 1. A method of treating a patient with AL amyloidosis, comprising: administering to the patient an effective dose of an antibody which competes with 2A4 (ATCC Accession No. PTA-9662) or 7D8 (ATCC Accession No. PTA-9468) for binding to human amyloid A peptide or human kappa or lambda light chain immunoglobulins, or which competes with 11-1F4 (ATCC Accession No. PTA-105) for binding to kappa light chain immunoglobulins; and administering a therapeutically effective dose of daratumumab to said patient 5 to 90 minutes after completion of the step of administering said antibody. Including, The patient has Mayo stage IV AL amyloidosis method.

277. The method of claim 277, wherein the patient has 6MWT≧150 meters and EF>50%.

278. 278. The method of claim 277, wherein the patient has a 6MWT > 30 meters and < 550 meters.

279. The method of claim 277, wherein the patient has EF>50%.

280. The method of claim 277, wherein the patient has a 6MWT≧150 meters.

281. The method of claim 277, wherein the selected patient has a cardiac complication.

282. The method of claim 277, wherein the selected patient has Mayo stage IV AL amyloidosis and has cardiac complications.

283. The method of claim 277, wherein the selected patient has Mayo stage IV AL amyloidosis, cardiac involvement and 6MWT > 30 meters and < 550 meters.

284. The method of any of the preceding claims, wherein the antibody comprises a light chain variable region comprising the three complementarity determining regions set forth as SEQ ID NOs: 3, 4 and 5 or SEQ ID NOs: 16, 17 and 18, and a heavy chain variable region comprising the three complementarity determining regions set forth as SEQ ID NOs: 6, 7 and 8 or SEQ ID NOs: 19, 20 and 21.

285. 10. The method of any preceding claim, wherein the light chain variable region comprises the amino acid sequence set forth as SEQ ID NO: 1 or 14.

286. 20. The method of any preceding claim, wherein the heavy chain variable region comprises the amino acid sequence set forth as SEQ ID NO: 2 or 15.

287. 10. The method of any preceding claim, wherein the light chain variable region comprises the amino acid sequence set forth as SEQ ID NO: 1 or 14, and the heavy chain variable region comprises the amino acid sequence set forth as SEQ ID NO: 2 or 15.

288. 10. The method of any preceding claim, wherein the antibody comprises a light chain comprising the amino acid sequence set forth as SEQ ID NO: 10, and a heavy chain comprising the amino acid sequence set forth as SEQ ID NO: 11, 12 or 13.

289. 10. The method of any preceding claim, wherein the antibody comprises a light chain comprising the amino acid sequence set forth as SEQ ID NO:10, and a heavy chain comprising the amino acid sequence set forth as SEQ ID NO:

12.

290. 20. The method of any of the preceding claims, wherein the patient has previously undergone or has concurrently undergone treatment with melphalan, prednisone, dexamethasone, bortezomib, cyclophosphamide, lenalidomide, doxorubicin, or combinations thereof.

291. 2. The method of any preceding claim, wherein the antibody comprises a light chain variable region comprising the three complementarity determining regions of 2A4, 7D8 or 11-1F4, and a heavy chain variable region comprising the three complementarity determining regions of 2A4, 7D8 or 11-1F4, respectively.

292. The method of any of the preceding claims, wherein the antibody is a humanized version of 2A4.

293. The method of any of the preceding claims, wherein the antibody is a humanized or chimeric version of 11-1F4.

294. 2. The method of any of the preceding claims, wherein the antibody is vilutamimab.

295. 20. The method of any of the preceding claims, wherein the patient shows improvement in SF-36PCS or SF-36v2 following treatment with the antibody.

296. The method of claim 234, wherein after 9 months of treatment, the change in the patient's score on the SF-36PCS or SF-36v2 is at least 5 points higher compared to a different patient at the same time point who has not been administered the antibody.

297. 2. The method of any preceding claim, wherein the therapeutically effective dose of the antibody is administered from a pharmaceutical formulation comprising the antibody at a concentration in the range of about 1 mg / mL to about 100 mg / mL.

298. 2. The method of any preceding claim, wherein the therapeutically effective dose of the antibody is from about 0.5 mg / kg to about 30 mg / kg, and the antibody is administered intravenously or subcutaneously at a frequency from about every week to about every three months.

299. 300. The method of claim 298, wherein the therapeutically effective dose of the antibody is present at a concentration of about 50 mg / mL.

300. 300. The method of any of claims 297-299, wherein the therapeutically effective dose is administered intravenously after transferring an amount of the formulation required for the dose from a vial to an intravenous infusion bag containing liquid.

301. The method of any of claims 297-300, wherein the therapeutically effective dose is about 24 mg / kg and the antibody is administered intravenously every 28 days.

302. 13. The method of any of the preceding claims, wherein the duration of the treatment is at least 15 months.

303. 13. The method of any of the preceding claims, wherein the duration of the treatment is at least 12 months.

304. 13. The method of any of the preceding claims, wherein the duration of the treatment is at least 9 months.

305. 13. The method of any of the preceding claims, wherein the duration of the treatment is at least six months.

306. 13. The method of any of the preceding claims, wherein the duration of the treatment is at least 3 months.

307. 2. The method of any preceding claim, wherein said duration is effective to achieve or maintain at least about a 3 point increase from baseline in SF-36PCS or SF-36v2.

308. The antibody is Fab, Fab', F(ab') ２ , F(ab)c, Dab, Nanobody or Fv.

309. 13. The method of any of the preceding claims, wherein treatment results in a 20% relative reduction in hospitalization.

310. 10. The method of any of the preceding claims, wherein treatment results in a 31% to 60% reduction in NTproBNP from baseline.

311. 10. The method of any of the preceding claims, wherein treatment results in a >60% reduction in the NTproBNP level from baseline to a nadir NTproBNP >400 pg / mL.

312. 2. The method of any of the preceding claims, wherein the treatment results in a nadir NTproBNP level of <400 pg / mL.

313. 10. The method of any of the preceding claims, wherein treatment results in at least a 5 point change to a 20 point change in the Kansas City Cardiomyopathy Questionnaire (KCCQ) score.

314. 13. The method of any preceding claim, resulting in at least a 33 meter improvement in the 6MWT after three months of treatment.

315. 13. The method of any preceding claim, resulting in at least a 33 meter improvement in the 6MWT after 6 months of treatment.

316. 13. The method of any preceding claim, resulting in at least a 33 meter improvement in the 6MWT after 9 months of treatment.

317. 13. The method of any preceding claim, resulting in at least a 33 meter improvement in the 6MWT after 12 months of treatment.

318. 13. The method of any preceding claim, resulting in at least a 33 meter improvement in the 6MWT after 15 months of treatment.

319. 13. The method of any preceding claim, resulting in at least a 33 meter improvement in the 6MWT after 18 months of treatment.

320. 2. The method of any of the preceding claims, wherein the patient is excluded from undergoing treatment if the patient has a NTproBNP level > 8500 pg / mL.

321. The method of any of the preceding claims, wherein the patient has not undergone an autologous transplant prior to administration of the effective dose of the antibody.

322. 2. The method of any of the preceding claims, wherein the patient is unable to receive an autologous transplant during treatment.

323. 2. The method of any of the preceding claims, wherein daratumumab is administered 120 minutes after completion of the step of administering the antibody.

324. 2. The method of any of the preceding claims, wherein daratumumab is administered 90 minutes after completion of the step of administering the antibody.

325. 2. The method of any of the preceding claims, wherein daratumumab is administered 75 minutes after completion of the step of administering the antibody.

326. 2. The method of any of the preceding claims, wherein daratumumab is administered 60 minutes after completion of the step of administering the antibody.

327. 2. The method of any of the preceding claims, wherein daratumumab is administered 30 minutes after completion of the step of administering the antibody.

328. 2. The method of any of the preceding claims, wherein daratumumab is administered 15 minutes after completion of the step of administering the antibody.

329. 2. The method of any of the preceding claims, wherein daratumumab is administered 10 minutes after completion of the step of administering the antibody.

330. 2. The method of any of the preceding claims, wherein daratumumab is administered 5 minutes after completion of the step of administering the antibody.

331. The patient meets the following criteria: (i) previously described or currently described clinical signs and symptoms that support a diagnosis of heart failure in the setting of a confirmed diagnosis of AL amyloidosis in the absence of any other possible explanation for heart failure; and (ii) Endomyocardial biopsy demonstrating AL amyloidosis or echocardiography demonstrating mean left ventricular wall thickness >12 mm in diastolic time in the absence of other causes.

2. The method of any preceding claim, having cardiac complications including:

332. The method of claim 331, wherein the other causes include severe hypertension or aortic valve stenosis.

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