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Safety and Efficacy of Daratumumab in Patients with Proliferative GN with Monoclonal Immunoglobulin Deposits

BACKGROUND: Treatment of proliferative GN with monoclonal Ig deposits (PGNMID) is not established. A monoclonal anti-CD38 antibody (daratumumab) is effective in treating multiple myeloma. Abnormal plasma cell clones may play a role in the pathogenesis of PGNMID. METHODS: We evaluated daratumumab’s s...

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Autores principales: Zand, Ladan, Rajkumar, S. Vincent, Leung, Nelson, Sethi, Sanjeev, El Ters, Mireille, Fervenza, Fernando C.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society of Nephrology 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8259683/
https://www.ncbi.nlm.nih.gov/pubmed/33685975
http://dx.doi.org/10.1681/ASN.2020101541
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author Zand, Ladan
Rajkumar, S. Vincent
Leung, Nelson
Sethi, Sanjeev
El Ters, Mireille
Fervenza, Fernando C.
author_facet Zand, Ladan
Rajkumar, S. Vincent
Leung, Nelson
Sethi, Sanjeev
El Ters, Mireille
Fervenza, Fernando C.
author_sort Zand, Ladan
collection PubMed
description BACKGROUND: Treatment of proliferative GN with monoclonal Ig deposits (PGNMID) is not established. A monoclonal anti-CD38 antibody (daratumumab) is effective in treating multiple myeloma. Abnormal plasma cell clones may play a role in the pathogenesis of PGNMID. METHODS: We evaluated daratumumab’s safety and efficacy in an open-label, phase 2 trial in 11 adults with PGNMID and one with C3 glomerulopathy (C3G) with monoclonal gammopathy. Patients had an eGFR >20 ml/min per 1.73 m(2) and proteinuria >1 g/d. They received daratumumab intravenously (16 mg/kg) once weekly for 8 weeks, and then every other week for eight additional doses. Primary outcome was safety, defined as major infections, grade 3 or 4 anemia, leukopenia, or thrombocytopenia. Secondary outcomes were rate of complete remission (proteinuria <500 mg/d with <15% decline in baseline eGFR) or partial remission (>50% reduction in 24-hour proteinuria with <30% decline in eGFR) and proteinuria at 6 and 12 months. RESULTS: One patient with C3G had GN unrelated to the monoclonal gammopathy, and one with PGNMID did not complete the first infusion. Five serious adverse events occurred. During the 12 months of the trial, six of the ten patients with PGNMID who received at least one dose of daratumumab had a partial response, and four had a complete response (an overall response rate of 100%). Three patients experienced relapse, two of whom re-entered partial remission after resuming daratumumab therapy. Proteinuria declined significantly, from a median of 4346 mg/d to 1264 mg/d by 12 months. CONCLUSIONS: Daratumumab demonstrated an acceptable safety profile and resulted in significant improvement in proteinuria while stabilizing kidney function in patients with PGNMID, suggesting the drug merits further investigation. CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER: Daratumumab in Treatment of PGNMID and C3 GN, NCT03095118
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spelling pubmed-82596832022-05-03 Safety and Efficacy of Daratumumab in Patients with Proliferative GN with Monoclonal Immunoglobulin Deposits Zand, Ladan Rajkumar, S. Vincent Leung, Nelson Sethi, Sanjeev El Ters, Mireille Fervenza, Fernando C. J Am Soc Nephrol Clinical Research BACKGROUND: Treatment of proliferative GN with monoclonal Ig deposits (PGNMID) is not established. A monoclonal anti-CD38 antibody (daratumumab) is effective in treating multiple myeloma. Abnormal plasma cell clones may play a role in the pathogenesis of PGNMID. METHODS: We evaluated daratumumab’s safety and efficacy in an open-label, phase 2 trial in 11 adults with PGNMID and one with C3 glomerulopathy (C3G) with monoclonal gammopathy. Patients had an eGFR >20 ml/min per 1.73 m(2) and proteinuria >1 g/d. They received daratumumab intravenously (16 mg/kg) once weekly for 8 weeks, and then every other week for eight additional doses. Primary outcome was safety, defined as major infections, grade 3 or 4 anemia, leukopenia, or thrombocytopenia. Secondary outcomes were rate of complete remission (proteinuria <500 mg/d with <15% decline in baseline eGFR) or partial remission (>50% reduction in 24-hour proteinuria with <30% decline in eGFR) and proteinuria at 6 and 12 months. RESULTS: One patient with C3G had GN unrelated to the monoclonal gammopathy, and one with PGNMID did not complete the first infusion. Five serious adverse events occurred. During the 12 months of the trial, six of the ten patients with PGNMID who received at least one dose of daratumumab had a partial response, and four had a complete response (an overall response rate of 100%). Three patients experienced relapse, two of whom re-entered partial remission after resuming daratumumab therapy. Proteinuria declined significantly, from a median of 4346 mg/d to 1264 mg/d by 12 months. CONCLUSIONS: Daratumumab demonstrated an acceptable safety profile and resulted in significant improvement in proteinuria while stabilizing kidney function in patients with PGNMID, suggesting the drug merits further investigation. CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER: Daratumumab in Treatment of PGNMID and C3 GN, NCT03095118 American Society of Nephrology 2021-05-03 2021-05-03 /pmc/articles/PMC8259683/ /pubmed/33685975 http://dx.doi.org/10.1681/ASN.2020101541 Text en Copyright © 2021 by the American Society of Nephrology This is an Open Access article: American Society of Nephrology
spellingShingle Clinical Research
Zand, Ladan
Rajkumar, S. Vincent
Leung, Nelson
Sethi, Sanjeev
El Ters, Mireille
Fervenza, Fernando C.
Safety and Efficacy of Daratumumab in Patients with Proliferative GN with Monoclonal Immunoglobulin Deposits
title Safety and Efficacy of Daratumumab in Patients with Proliferative GN with Monoclonal Immunoglobulin Deposits
title_full Safety and Efficacy of Daratumumab in Patients with Proliferative GN with Monoclonal Immunoglobulin Deposits
title_fullStr Safety and Efficacy of Daratumumab in Patients with Proliferative GN with Monoclonal Immunoglobulin Deposits
title_full_unstemmed Safety and Efficacy of Daratumumab in Patients with Proliferative GN with Monoclonal Immunoglobulin Deposits
title_short Safety and Efficacy of Daratumumab in Patients with Proliferative GN with Monoclonal Immunoglobulin Deposits
title_sort safety and efficacy of daratumumab in patients with proliferative gn with monoclonal immunoglobulin deposits
topic Clinical Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8259683/
https://www.ncbi.nlm.nih.gov/pubmed/33685975
http://dx.doi.org/10.1681/ASN.2020101541
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