Idecabtagene vicleucel (ide-cel) and ciltacabtagene autoleucel (cilta-cel) have revolutionized the treatment of relapsed/refractory multiple myeloma (RRMM), but direct comparisons are lacking. Leveraging an international multicenter RRMM cohort, we compared the outcome of ide-cel (n = 162) versus cilta-cel (n = 42). Co-primary efficacy endpoints of the study were overall response rate (ORR) and progression-free survival (PFS). Co-primary safety endpoints were the incidence of cytokine release syndrome (CRS) and immune-effector cell-associated neurotoxicity syndrome (ICANS). Median turnaround time between apheresis and infusion was 47 days for ide-cel versus 68 days for cilta-cel (p < 0.001). Cilta-cel showed significantly higher ORR (93% vs. 79%; p < 0.001), with complete response at Day 30 of 48% versus 26% (p < 0.001). The 10-month PFS and overall survival (OS) was 82% and 90% for cilta-cel versus 47% and 77% ide-cel (p < 0.001 and p = 0.06), and improved outcome for cilta-cel was confirmed after multivariable adjustment. Incidence of CRS and ICANS appeared similar (81% and 19% for cilta-cel versus 85% and 19% for ide-cel), while 10% and 7% in the cilta-cel group versus 4% and 2% in the ide-cel group showed severe CRS and ICANS grade 3-4, with CRS occurring significantly earlier for ide-cel (median, 2 days vs. 4 days; p < 0.001). Nonrelapse mortality was 5% for cilta-cel versus 3% for ide-cel (p = 0.51). Cilta-cel showed later peak of CAR-T expansion at Day 14 versus Day 7 for ide-cel, while cilta-cel expansion was associated with ICANS. Our study provides real-world evidence that cilta-cel was associated with superior outcomes and distinct cellular dynamics versus ide-cel in triple-class exposed RRMM.

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