Salvage Therapies including Retreatment with BCMA-directed Approaches Following BCMA CAR-T Relapses for Multiple Myeloma

Abstract

For patients with relapsed/refractory multiple myeloma (RRMM) with relapse following B-cell maturation antigen (BCMA)-directed chimeric antigen receptor T-cell therapies (CAR-T), optimal salvage treatment strategies remain unclear. BCMA-directed CAR-T and bispecific antibodies (BsAb) 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 months-not reached (NR)). 58 patients received subsequent myeloma-directed therapies, with a total of 265 lines-of-therapy (LOTs). The overall response rate for first-line salvage therapy was 41% (CI: 28-55%). Among all LOTs, high response rates were observed among those receiving another BCMA-directed CAR-T (89%), BCMA-directed BsAb (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 one line of salvage BCMA-directed therapy; median PFS was 8.3 months (CI: 7.9 months-NR), 3.6 months (CI: 1.4 months-NR), and 1 month (CI: 0.9 months-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 BsAb can be effective salvage options post-BCMA-directed CAR-T relapse; however, DORs appear limited and further studies with new combinations and alternative targets are warranted.