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

• Published in: Blood advances Vol. 8; no. 9; pp. 2207 - 2216
• Main Authors: Reyes, Kevin R., Liu, Yen-Chun, Huang, Chiung-Yu, Banerjee, Rahul, Martin, Thomas, Wong, Sandy W., Wolf, Jeffrey L., Arora, Shagun, Shah, Nina, Chari, Ajai, Chung, Alfred
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 14.05.2024; The American Society of Hematology
• Subjects: Adult; Aged; B-Cell Maturation Antigen - antagonists & inhibitors; B-Cell Maturation Antigen - immunology; Female; Humans; Immunotherapy, Adoptive - methods; Lymphoid Neoplasia; Male; Middle Aged; Multiple Myeloma - immunology; Multiple Myeloma - mortality; Multiple Myeloma - therapy; Receptors, Chimeric Antigen - therapeutic use; Recurrence; Retreatment; Retrospective Studies; Salvage Therapy - methods; Treatment Outcome
• ISSN: 2473-9529; 2473-9537
• DOI: 10.1182/bloodadvances.2023012066

•Retreatment with BCMA-directed therapies after prior BCMA-directed CAR-T can elicit high response rates in patients with multiple myeloma.•Despite high response rates, durability of responses to salvage therapies after BCMA-directed CAR-T relapses are currently suboptimal. [Display omitted] 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.