A phase Ib trial of isatuximab, bendamustine, and prednisone in relapsed/refractory multiple myeloma.

Autor: Goldsmith SR; Division of Oncology, Department of Medicine, Washington University in Saint Louis, St. Louis, MO, USA.; Division of Multiple Myeloma, Department of Hematology & Hematopoietic Transplantation, City of Hope, Duarte, CA, USA., Slade MJ; Division of Oncology, Department of Medicine, Washington University in Saint Louis, St. Louis, MO, USA. sladem@wustl.edu., Fiala M; Division of Oncology, Department of Medicine, Washington University in Saint Louis, St. Louis, MO, USA., Harding M; Division of Oncology, Department of Medicine, Washington University in Saint Louis, St. Louis, MO, USA., Crees ZD; Division of Oncology, Department of Medicine, Washington University in Saint Louis, St. Louis, MO, USA., Schroeder MA; Division of Oncology, Department of Medicine, Washington University in Saint Louis, St. Louis, MO, USA., Stockerl-Goldstein K; Division of Oncology, Department of Medicine, Washington University in Saint Louis, St. Louis, MO, USA., Vij R; Division of Oncology, Department of Medicine, Washington University in Saint Louis, St. Louis, MO, USA.
Jazyk: angličtina
Zdroj: Annals of hematology [Ann Hematol] 2024 Nov; Vol. 103 (11), pp. 4557-4565. Date of Electronic Publication: 2024 Sep 04.
DOI: 10.1007/s00277-024-05975-7
Abstrakt: Introduction: Patients with triple-class refractory (TCR) multiple myeloma (MM) often need cytoreductive chemotherapy for rapid disease control. Bendamustine is an outpatient-administered, bifunctional alkylator and isatuximab is an anti-CD38 monoclonal antibody with unique cytotoxicity characteristics. We hypothesized that isatuximab-bendamustine-prednisone would be well-tolerated regimen in TCR MM, and conducted single-center, phase Ib, investigator-initiated study.
Patients/methods: Patients had TCR MM and last daratumumab exposure ≥ 6 weeks. This study was conducted as a 3 + 3 design to establish the maximally tolerated dose (MTD) and/or recommended phase 2 dose (RP2D). Isatuximab 10 mg/kg IV was administered weekly (cycle 1), and every 2 weeks thereafter. Bendamustine was administered on days 1 and 2 at 3 dose levels (DL): 50, 75, and 100 mg/m 2 . Methylprednisolone was administered as 125 mg on day 1 and prednisone 60 mg days 2-4. Common definitions were used for DLTs, adverse events (CTCAE v 5.0), and disease response.
Results: Fifteen patients were treated (3 DL1, 6 DL2, 6 DL3). Median age was 71, 53% had high-risk cytogenetics, and 34% had prior BCMA-targeting therapy. One DLT was observed at DL2 (Grade 3 thrombocytopenia plus bleeding). There were no Grade 5 treatment-related AEs. The MTD was not reached. The overall response rate was 20% (3/15) including one stringent complete response. The median PFS was 2.5 months (95% CI 0.9-4.1 months).
Conclusion: We demonstrated the safety and tolerability of isatuximab-bendamustine-prednisone. Toxicities were mild and manageable with limited intervention. The study was discontinued due to slow accrual. However, we observed responses even among highly refractory patients.
Clinical Trial Registration: This study was registered on clinicaltrials.gov as NCT04083898 on 9/6/2019.
(© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)
Databáze: MEDLINE
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