CAR T-Cell Therapy vs. Standard Care in Relapsed Myeloma

B-cell maturation antigen–directed CAR T-cell therapy is an effective option for relapsed and refractory multiple myeloma. To test the benefit in less-heavily pretreated patients, investigators conducted an industry-sponsored, multinational, open-label, phase 3 trial comparing a single infusion of ciltacabtagene autoleucel (cilta-cel) with physician's choice of either pomalidomide, bortezomib, and dexamethasone (PVd) or daratumumab, pomalidomide, and dexamethasone (DPd). Eligible patients had disease that progressed after 1 to 3 prior lines of therapy that included a proteasome inhibitor and an immunomodulatory drug and disease that was resistant to lenalidomide. Bridging therapy with one of the standard regimens was permitted after apheresis. Crossover to cilta-cel was not allowed for patients who did not respond to standard care.

A total of 419 patients were randomized to cilta-cel or standard care (most received DPd). Cilta-cel was administered to 176 of the 208 patients randomized to that arm (85%); 32 patients left the trial before treatment due to disease progression during CAR T-cell manufacture. At a median follow-up of 16 months, progression-free survival (PFS), the primary endpoint, was significantly improved with cilta-cel compared with standard care (not reached vs. 11.8 months; hazard ratio, 0.26; P<0.001). Among the intent-to-treat populations, the 12-month PFS was significantly higher with cilta-cel (75.9% vs. 48.6%), as was the rate of complete response (73.1% vs. 21.8%); there was no difference in 12-month overall survival. Measurable residual disease (MRD) was not detected in 60.6% of the cilta-cel arm versus 15.6% of the standard-care arm. Toxicities were as anticipated for these regimens, with cytokine release syndrome in 76% (grade 1–2 in all but 1%) and grade 1–2 neurotoxicity in 17.7%.