Retrospective analysis of outcomes of salvage treatment after BCMA-specific CAR-T therapy for relapsed or refractory multiple myeloma

CAR-T therapy targeting BCMA has shown profound efficacy and manageable toxicity in patients with relapsed or refractory multiple myeloma. Determining the best course of treatment for post-CAR-T therapy remains a significant challenge. Retrospective analysis of patients enrolled in the phase 1 LEGEND -2 study compared salvage treatments in patients with RRMM who progressed after LCAR-B38M CAR-T therapy in the Xi’an Jiaotong University cohort of the phase 1 LEGEND-2 trial. Among 45 patients, 34 (76%) had progressive disease (PD). ORR to salvage therapy was 50.0%. Median progression-free survival after starting salvage therapy was 16.3 months (panel A). Patients with complete response had significantly longer PFS than those with partial response (panel B). Median overall survival was 47.2 months (panel C). Patients without PD had significantly longer OS than those with PD (panel D). The median PFS of patients receiving salvage proteasome inhibitor-based combination therapy was significantly longer (28.2 months) than that of patients receiving a second BCMA CAR-T (3.9 months; p=0.0022) or chemotherapy (1.67 months; p=0.0001). The authors conclude that salvage therapy after BCMA-directed CAR-T had moderate efficacy, with better outcomes for proteasome inihibitor-based salvage regimens.