Real-World Outcomes of Sequential BCMA-directed therapies in Relapsed Refractory Multiple Myeloma After Belantamab Exposure.

Background: While B-cell maturation antigen (BCMA) directed therapies are increasingly utilized for multiple myeloma, outcomes with sequential treatments with BCMA-directed therapies remain an area of active investigation.

Methods: In this multicenter retrospective analysis, we evaluated the real-world outcomes of patients treated with BCMA-directed therapies including CAR T and bispecific antibody (BsAb) following progression on the antibody-drug conjugate belantamab mafodotin. A total of 23 patients (14 CAR T, 9 BsAb) were included in the analysis.

Results: The median patient age was 68 (range 37-82) years, with 43% having high-risk cytogenetics, 87% having received ≥4 prior lines of therapy, and 35% with extramedullary disease at the time of treatment. The overall response rate (ORR) for the entire population was 65%, 44% in the BsAb and 79% in the CAR T subgroup. With a median follow-up of 24 months, median progression-free survival (PFS) and overall survival (OS) were 5 (range 2-10) months and 28 (range 16-NR) months, respectively. There was no difference in median PFS between patients who received a BsAb vs CAR T (p=0.8), or based on time from belantamab to BCMA therapy (<6 months vs ≥6 months, p=0.8).

Conclusion: Treatment with BCMA-directed BsAb or CAR T remains feasible for RRMM patients after progression on belantamab. However, outcomes remain inferior compared to those without prior BCMA exposure and were not affected by choice of therapy or time since last BCMA exposure.