Debulking strategy prior to anti-BCMA/CD3 bispecific antibodies in extramedullary and/or high tumor burden RRMM: a retrospective cohort study

T-cell redirecting immunotherapies have improved outcomes in relapsed/refractory multiple myeloma (RRMM), yet patients with extramedullary disease (EMD) and/or high tumor burden continue to fare poorly. We evaluated chemotherapy-based tumor debulking prior to anti-BCMA/CD3 bispecific antibody (BsAb) therapy in this high-risk population. In this multicenter retrospective study (15 IFM centers), RRMM patients receiving BsAb therapy after chemotherapy within the prior month were analyzed. High tumor burden included medullary/para-medullary disease or elevated monoclonal protein. High-risk cytogenetics comprised del(17p), 1q21 gain/amplification, t(4;14), or t(14;16). Forty-four patients (median age 67) were included: 93% were triple-class refractory, 50% had EMD, and 50% had high-risk cytogenetics. Chemotherapy regimens included alkylators (89%), anthracyclines (34%), and etoposide (50%). Teclistamab (70%) or elranatamab (30%) was initiated after a median of 28 days post-chemotherapy. At 12 months median follow-up, ORR post-chemotherapy was 32%. ORR with BsAb reached 64% after cycle 1, 73% after cycle 3, and 87% after cycle 6. Median progression-free survival was 10.2 months; median overall survival, 20.1 months. Chemotherapy-based debulking prior to anti-BCMA/CD3 BsAb is feasible and safe, achieving high response rates and durable outcomes in high-risk RRMM.