CAR T-Cell Therapy in Relapsed/Refractory Myeloma

Patients with relapse of myeloma after multiple lines of therapy had limited treatment options prior to the availability of CAR T-cell products. Now, in an industry-sponsored, multicenter, phase 3 trial, 386 patients with relapsed or refractory myeloma were randomized 2:1 to the anti–B-cell maturation antigen-directed CAR-T agent idecabtagene vicleucel (ide-cel) or one of five standard therapeutic regimens. Eligible patients had received two to four prior regimens that included immunomodulatory agents, proteasome inhibitors, and the anti-CD38 monoclonal antibody daratumumab; most patients were refractory to their most recent treatment.

With a median follow-up of 18.6 months, progression-free survival (PFS), the primary outcome, was significantly longer with ide-cel than standard therapy (median, 13.3 vs. 4.4 months; P<0.001). Overall response rate was also significantly improved with ide-cel (71% vs. 42%), as was the rate of complete remission (39% vs. 5%). Cytokine release syndrome occurred in 88% of ide-cel administrations, although only 5% were grade 3 or higher. Neurologic toxicity, another recognized side effect of CAR-T therapy, was observed in 15% of administrations (3% were ≥grade 3).