Early daratumumab therapy improves renal outcomes in newly diagnosed patients with myeloma admitted with kidney injury

Abstract: Cast nephropathy is the most common cause of acute kidney injury (AKI) in patients with multiple myeloma (MM). A prompt reversal of renal injury is paramount for improving clinical outcomes. Daratumumab, an anti-CD38 monoclonal antibody, has significant clinical efficacy in MM. We describe...

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Main Authors: E. Bridget Kim, Jack E. Malespini, Matthew Lei, Samuel S. Han, Cole W. Minsky, Andrew R. Branagan, Elizabeth K. O’Donnell, Diana Cirstea, Noopur S. Raje, Andrew J. Yee
Format: Article
Language:English
Published: Elsevier 2025-07-01
Series:Blood Advances
Online Access:http://www.sciencedirect.com/science/article/pii/S2473952925001594
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author E. Bridget Kim
Jack E. Malespini
Matthew Lei
Samuel S. Han
Cole W. Minsky
Andrew R. Branagan
Elizabeth K. O’Donnell
Diana Cirstea
Noopur S. Raje
Andrew J. Yee
author_facet E. Bridget Kim
Jack E. Malespini
Matthew Lei
Samuel S. Han
Cole W. Minsky
Andrew R. Branagan
Elizabeth K. O’Donnell
Diana Cirstea
Noopur S. Raje
Andrew J. Yee
author_sort E. Bridget Kim
collection DOAJ
description Abstract: Cast nephropathy is the most common cause of acute kidney injury (AKI) in patients with multiple myeloma (MM). A prompt reversal of renal injury is paramount for improving clinical outcomes. Daratumumab, an anti-CD38 monoclonal antibody, has significant clinical efficacy in MM. We describe the effects of daratumumab-based therapy in 20 patients admitted with a new diagnosis of MM and AKI with a median creatinine of 6.5 mg/dL. All patients (100%) achieved serum free light chain (sFLC) reduction ≥50% within the first cycle, with a median time to sFLC reduction ≥50% of 3 days (95% confidence interval [CI], 3-7). Of 17 patients, 15 (88%) achieved sFLC reduction ≤500 mg/L after 1 cycle of treatment. The median time to sFLC reduction ≤500 mg/L was 14.5 days (95% CI, 9-49). The overall renal response at 3 months was 85% (n = 17), with complete, partial, and minor responses in 50% (n = 10), 10% (n = 2), and 25% (n = 5), respectively. Of the 9 patients who required dialysis at presentation, 4 of 7 (57.1%) and 6 of 7 (85.7%) were dialysis independent at 3 and 12 months, respectively. Hematologic overall response rate was 100%, with very good partial response (VGPR) in 90%. With a median follow-up of 25 months, progression-free survival was 46.5 months (95% CI, 11.9 to not reached), and the 2-year overall survival was 83.7% (95% CI, 68.4-100). These findings highlight the importance of early initiation of daratumumab-based treatment in patients with MM and AKI to induce rapid and significant reductions in sFLCs, improve renal outcomes, and provide an approach without plasmapheresis.
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spelling doaj-art-44ddbd0f4e124d7c88db0e2927b7d9762025-08-20T02:20:51ZengElsevierBlood Advances2473-95292025-07-019133129313510.1182/bloodadvances.2025015901Early daratumumab therapy improves renal outcomes in newly diagnosed patients with myeloma admitted with kidney injuryE. Bridget Kim0Jack E. Malespini1Matthew Lei2Samuel S. Han3Cole W. Minsky4Andrew R. Branagan5Elizabeth K. O’Donnell6Diana Cirstea7Noopur S. Raje8Andrew J. Yee9Center for Multiple Myeloma, Massachusetts General Hospital Cancer Center, Boston, MACenter for Multiple Myeloma, Massachusetts General Hospital Cancer Center, Boston, MACenter for Multiple Myeloma, Massachusetts General Hospital Cancer Center, Boston, MACenter for Multiple Myeloma, Massachusetts General Hospital Cancer Center, Boston, MACenter for Multiple Myeloma, Massachusetts General Hospital Cancer Center, Boston, MACenter for Multiple Myeloma, Massachusetts General Hospital Cancer Center, Boston, MA; Harvard Medical School, Boston, MACenter for Multiple Myeloma, Massachusetts General Hospital Cancer Center, Boston, MA; Harvard Medical School, Boston, MACenter for Multiple Myeloma, Massachusetts General Hospital Cancer Center, Boston, MA; Harvard Medical School, Boston, MACenter for Multiple Myeloma, Massachusetts General Hospital Cancer Center, Boston, MA; Harvard Medical School, Boston, MACenter for Multiple Myeloma, Massachusetts General Hospital Cancer Center, Boston, MA; Harvard Medical School, Boston, MA; Correspondence: Andrew J. Yee, Massachusetts General Hospital Cancer Center Boston, 55 Fruit St, Boston, MA 02114;Abstract: Cast nephropathy is the most common cause of acute kidney injury (AKI) in patients with multiple myeloma (MM). A prompt reversal of renal injury is paramount for improving clinical outcomes. Daratumumab, an anti-CD38 monoclonal antibody, has significant clinical efficacy in MM. We describe the effects of daratumumab-based therapy in 20 patients admitted with a new diagnosis of MM and AKI with a median creatinine of 6.5 mg/dL. All patients (100%) achieved serum free light chain (sFLC) reduction ≥50% within the first cycle, with a median time to sFLC reduction ≥50% of 3 days (95% confidence interval [CI], 3-7). Of 17 patients, 15 (88%) achieved sFLC reduction ≤500 mg/L after 1 cycle of treatment. The median time to sFLC reduction ≤500 mg/L was 14.5 days (95% CI, 9-49). The overall renal response at 3 months was 85% (n = 17), with complete, partial, and minor responses in 50% (n = 10), 10% (n = 2), and 25% (n = 5), respectively. Of the 9 patients who required dialysis at presentation, 4 of 7 (57.1%) and 6 of 7 (85.7%) were dialysis independent at 3 and 12 months, respectively. Hematologic overall response rate was 100%, with very good partial response (VGPR) in 90%. With a median follow-up of 25 months, progression-free survival was 46.5 months (95% CI, 11.9 to not reached), and the 2-year overall survival was 83.7% (95% CI, 68.4-100). These findings highlight the importance of early initiation of daratumumab-based treatment in patients with MM and AKI to induce rapid and significant reductions in sFLCs, improve renal outcomes, and provide an approach without plasmapheresis.http://www.sciencedirect.com/science/article/pii/S2473952925001594
spellingShingle E. Bridget Kim
Jack E. Malespini
Matthew Lei
Samuel S. Han
Cole W. Minsky
Andrew R. Branagan
Elizabeth K. O’Donnell
Diana Cirstea
Noopur S. Raje
Andrew J. Yee
Early daratumumab therapy improves renal outcomes in newly diagnosed patients with myeloma admitted with kidney injury
Blood Advances
title Early daratumumab therapy improves renal outcomes in newly diagnosed patients with myeloma admitted with kidney injury
title_full Early daratumumab therapy improves renal outcomes in newly diagnosed patients with myeloma admitted with kidney injury
title_fullStr Early daratumumab therapy improves renal outcomes in newly diagnosed patients with myeloma admitted with kidney injury
title_full_unstemmed Early daratumumab therapy improves renal outcomes in newly diagnosed patients with myeloma admitted with kidney injury
title_short Early daratumumab therapy improves renal outcomes in newly diagnosed patients with myeloma admitted with kidney injury
title_sort early daratumumab therapy improves renal outcomes in newly diagnosed patients with myeloma admitted with kidney injury
url http://www.sciencedirect.com/science/article/pii/S2473952925001594
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