Idecabtagene vicleucel or ciltacabtagene autoleucel for relapsed or refractory multiple myeloma: An international multicenter study

Abstract

Abstract 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.