Comparative efficacy of idecabtagene vicleucel and ciltacabtagene autoleucel in relapsed/refractory multiple myeloma: Real-world analysis of overall survival and time to next treatment.

e19532 Background: Relapsed/ refractory multiple myeloma (RRMM) is a challenging disease to manage with limited treatment options. Chimeric antigen receptor T-cell (CAR-T) therapies, idecabtagene vicleucel (IC) and ciltacabtagene autoleucel (CC) are approved for overlapping indications in RRMM patients (pts), but comparative real-world (RW) efficacy data are sparse. This study evaluates overall survival (OS) and time to next treatment (TTNT) for IC versus CC in a RW setting, providing insights to inform therapeutic decision-making. Methods: A retrospective analysis was done using TriNetX, a global RW data platform. Adult RRMM pts (ICD-10 code C90.0) treated with IC (n=485) or CC (n=392) between 2021 and 2024 were included. Propensity score matching with 37 variables (demographics, prior treatments, organ function, performance status, paraprotein studies, albumin, β-2 microglobulin) balanced cohorts yielding 252 pts in each group. OS was defined as time from CAR-T infusion to death, and TTNT was defined as time from CAR-T to next MM-specific treatment or death. Kaplan-Meier survival analysis with log-rank tests assessed differences, with hazard ratios (HR) calculated using proportional hazards models. Progression-free survival was not used due to platform limitations. Results: After matching, baseline characteristics were well-balanced between groups, shown in Table 1. Median follow up (f/u) was 14.2 months (IQR- 16.3) for IC and 8.5 months (IQR-13) for CC. 48 patients in IC and 32 patients in CC died during f/u; median OS was not reached (NR) in either group with estimated 2-year survival probabilities of 77% for IC and 73% for CC (HR: 1.051; 95% CI: 0.636–1.734; p=0.847). Median TTNT was 17.7 months for IC and NR for CC. 118 pts in IC and 58 pts in CC had a TTNT event. At 2 years, TTNT probabilities were 36% for IC and 52% for CC, with CC demonstrating a significant advantage (P<0.0001; HR for CC vs IC: 0.60; 95% CI: 0.44-0.83). Conclusions: In this RW analysis, CC showed improved durability in delaying subsequent therapy compared to IC, as reflected by a significant TTNT benefit. However, this advantage did not translate into improved OS during the follow-up period. Differences in follow-up duration and RW data limitations, including potential missing data, may have influenced outcomes. Prospective studies are needed to confirm these results and identify optimal patient-specific strategies for CAR-T therapy in RRMM. Characteristic Ide-cel (IC) Cilta-cel (CC) P-value Age at CAR-T (mean +/-SD yrs) 65.3 +/-9.4 65.2 +/-9.5 0.94 Female vs Male (%) 42 vs 58 44 vs 56 0.65 White and African American race (%) 76 vs 15 76 vs 17 1.0/0.46 Bortezomib/ Carfilzomib/ Ixazomib (%) 37/28/8 38/30/8 0.93/0.62/0.87 Lenalidomide/Pomalidomide/Thalidomide (%) 50/44/8 51/45/7 0.72/0.86/0.50 Daratumumab/ Isatuximab/ Elotuzumab (%) 36/4/6 36/4/6 0.85/1.0/0.71 Belantamab/Teclistamab/Talquetamab (%) 4/4/4 4/4/4 1.0/1.0/1.0 Elevated LDH (>220U; %) 75 75 0.92 Albumin ≥3.5 g/dL/ β2-microglobulin ≥5.5 mg/L 95/15 95/15 0.69/1.0