B-cell maturation antigen-targeted CAR T cell as a salvage therapy for progressive multiple myeloma after anti-G proteincoupled receptor, class C group 5 member D CAR T-cell therapy

Abstract

Repeat infusion of chimeric antigen receptor (CAR) T-cell is effective for patients with refractory or relapsed multiple myeloma (RRMM) after failing a prior CAR Tcell therapy. It is unknown whether B-cell maturation antigen (BCMA) CAR T-cell is effective for patients with RRMM after anti-G protein-coupled receptor, class C group 5 member D (GPRC5D) CAR-T cell therapy. In this study, 20 subjects with RRMM after a prior anti-GPRC5D CAR T-cell therapy received BCMA-targeted CAR T-cell therapy as a salvage treatment. During a median follow-up of 13.4 months (IQR 3.6-21.2), 13 subjects showed responses including 9 with stringent complete response (sCR) and 4 with partial response. The median duration of response was 10.2 months (95% CI, 2.6 - not reached). The median progression-free survival (PFS) were 9.2 months (95% CI, 3.0-13.6) in all subjects and 20.8 months (95% CI, 5.3 - not reached) in subjects with sCR. There is no statistic difference in overall response rate (ORR) and median PFS between this study and our previous study, which enrolled 37 subjects with RRMM receiving anti-GPRC5D CAR T-cells after failing anti-BCMA CAR T-cell therapies (ORR: 65% vs 84%, P = 0.18; PFS: 9.2 vs 4.5 months, P = 0.93). The most common adverse events were grade ≥3 haematological toxicities (n=18). Fourteen subjects (78%) had cytokine release syndrome (grade ≥3, n=1). In conclusion, anti-BCMA CAR T-cell therapy was effective for RRMM after failing an anti-GPRC5D CAR T-cell therapy, and the safety profile was acceptable.