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

person Sankalp Arora The University of Alabama at Birmingham, Department of Medicine, Birmingham, AL info_outline Sankalp Arora, Smith Giri, Kelly Nicole Godby, Gayathri Ravi, Luciano J. Costa, Susan Bal

Authors person Sankalp Arora The University of Alabama at Birmingham, Department of Medicine, Birmingham, AL info_outline Sankalp Arora, Smith Giri, Kelly Nicole Godby, Gayathri Ravi, Luciano J. Costa, Susan Bal Organizations The University of Alabama at Birmingham, Department of Medicine, Birmingham, AL, University of Alabama at Birmingham, Alabama, AL, University of Alabama at Birmingham, Division of Hematology/Oncology, Department of Medicine, Birmingham, AL, The University of Alabama at Birmingham, Birmingham, AL, University of Alabama at Birmingham, Birmingham, AL Abstract Disclosures Research Funding No funding received 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 1 st 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. Post BCMA therapies. Treatment regimen post BCMA TRT Number of pts (%) ORR mPFS (mos) mOS (mos) Cytotoxic chemotherapy 15 (48) 33% 2.1 3.9 Selinexor 6 (19) 50% 1.9 8.1 Non-BCMA TRT 7 (23) 43% 2.4 10.5