Salvage therapies including retreatment with BCMA-directed approaches after BCMA CAR-T relapses for multiple myeloma

Author:

Reyes Kevin R.1ORCID,Liu Yen-Chun2,Huang Chiung-Yu3ORCID,Banerjee Rahul45ORCID,Martin Thomas4,Wong Sandy W.4,Wolf Jeffrey L.4,Arora Shagun4ORCID,Shah Nina4,Chari Ajai4,Chung Alfred4ORCID

Affiliation:

1. 1School of Medicine, University of California San Francisco, San Francisco, CA

2. 2Department of Statistical Science, Duke University, Durham, NC

3. 3Department of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, CA

4. 4Division of Hematology/Oncology, University of California San Francisco, San Francisco, CA

5. 5Division of Medical Oncology, Department of Medicine, University of Washington, Seattle, WA

Abstract

Abstract For patients with relapsed/refractory multiple myeloma with a relapse after B-cell maturation antigen (BCMA)–directed chimeric antigen receptor T-cell therapy (CAR-T), optimal salvage treatment strategies remain unclear. BCMA-directed CAR-T and bispecific antibodies (BsAbs) are now commercially available, and the outcomes for retreatment with BCMA-directed approaches are not well studied. We performed a retrospective analysis of 68 patients with relapsed disease after BCMA-directed CAR-T to evaluate outcomes and responses to salvage therapies. With a median follow-up of 13.5 months, median overall survival from time of relapse until death was 18 months (95% confidence interval [CI], 13.2 to not reached [NR]). Fifty-eight patients received subsequent myeloma-directed therapies, with a total of 265 lines of therapy (LOTs). The overall response rate for firstline salvage therapy was 41% (95% CI, 28-55). Among all LOTs, high response rates were observed among those receiving another BCMA-directed CAR-T (89%), BCMA-directed BsAbs (60%), CD38-directed combinations (80% when combined with BsAb; 50% when combined with immunomodulatory drugs and/or proteasome inhibitors), and alkylator-combinations (50% overall; 69% with high-dose alkylators). Thirty-four patients received at least 1 line of salvage BCMA-directed therapy; median progression-free survival was 8.3 months (95% CI, 7.9 to NR), 3.6 months (95% CI, 1.4 to NR), and 1 month (95% CI, 0.9 to NR) with median duration of response (DOR) of 8 months, 4.4 months, and 2.8 months for subsequent BCMA-directed CAR-T, BsAb, and belantamab mafadotin, respectively. Retreatment with BCMA-directed CAR-T and BsAbs can be effective salvage options after BCMA-directed CAR-T relapse; however, DORs appear limited, and further studies with new combinations and alternative targets are warranted.

Publisher

American Society of Hematology

Cited by 5 articles. 订阅此论文施引文献 订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献

1. Bispecific T-Cell Engagers: Sequencing, BCMA, GPRC5D, and Resistance;Clinical Lymphoma Myeloma and Leukemia;2024-09

2. Allogeneic stem cell transplantation in multiple myeloma: is there still a place?;Frontiers in Oncology;2024-06-04

3. Advances in research on factors affecting chimeric antigen receptor T‐cell efficacy;Cancer Medicine;2024-06

4. Charting the Course: Sequencing Immunotherapy for Multiple Myeloma;American Society of Clinical Oncology Educational Book;2024-06

5. Sequence not salvage;British Journal of Haematology;2024-04-02

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