Beyond BCMA: Outcomes of relapsed/refractory multiple myeloma after progression on anti-BCMA T cell redirecting therapy.

e20026 Background: Immunotherapeutic strategies targeting B-cell Maturation Antigen (BCMA) have revolutionized the management of triple class refractory multiple myeloma (MM). However, the outcomes of patients (pts) who experience progressive disease (PD) after anti BCMA T-cell redirecting therapy (TRT) are unknown. Methods: We retrospectively analyzed pt and disease characteristics as well as post-BCMA outcomes for adults with relapsed/refractory MM who experienced PD after BCMA TRT at our institution. Responses were assessed by International Myeloma Working Group criteria. Survival outcomes were measured using Kaplan-Meier estimator. Results: Between 8/2018-2/2022, 63 pts received anti-BCMA TRT. With median follow up of 11.3 months (mos), 25 pts (40%) remain alive without MM progression and 7 pts (11%) died without progression. A total of 31 pts experienced PD and are the subject of this analysis. The median time from diagnosis to BCMA TRT was 36 mos with median 6 prior LoT (3-11) and 81% penta-refractory. The median time from BCMA TRT (CAR-T in 61%, bispecific T-cell engager in 39%) to post-BCMA PD was 3.19 mos. Overall response rate (ORR) to BCMA TRT for these 31 pts was 52% (≥very good partial response; VGPR 39%). Among the pts with post-BCMA PD, 45% had high risk cytogenetics (CHR), 45% extramedullary plasmacytomas (EMP), and 81% penta-refractory disease. The median overall survival (mOS) from time of post-BCMA PD is 4.3 mos (median follow up 8 mos). Eight pts with PD were not candidates for additional therapy and had mOS of 1 mo. The remaining 23 pts with PD were able to receive 1 or more additional LoT. For this group, median age was 64 years (42-77), 70% male, 52% had CHR, 22% ISS stage III. The median prior LoT was 6 (3-11) and 74% were penta-refractory. Median time from initiation of BCMA TRT to start of first post BCMA therapy was 4.3 mos (0.6-17). The most commonly used agents in next LoT are shown in the table. ORR to subsequent LoT was 35% (17% ≥VGPR). With 5 mos median follow up, 13 pts (57%) have died, median PFS and mOS to 1st post BCMA LoT is 2.2 mos and 8.1 mos. Eight pts were able to proceed with experimental therapies (88% non-BCMA TRT) with higher ORR 50% (25% ≥VGPR) resulting in longer mPFS (3.3 mos) and mOS (11 mos) with median follow up of 10.9 mos. One pt received BCMA directed CAR-T after progression on anti-BCMA T-cell engager and did not respond. Conclusions: The outcomes of pts progressing on BCMA TRT remain poor. However, failure of BCMA targeting TRT does not preclude response to T-cell engagers against non-BCMA targets. Participation in clinical trials evaluating novel mechanisms remains the best strategy for this challenging population.[Table: see text]