CAR-T Therapy Showdown: Comparative Efficacy and Safety of of Ide-Cel (Idecabtagene vicleucel) and Cilta-Cel (Ciltacabtagene Autoleucel) in Relapsed/Refractory Multiple Myeloma (RRMM): A Real-World Study

Purpose/Objective: Although treatment and prognosis have improved significantly over the last two decades, multiple myeloma (MM) remains an incurable disease with high relapse rates. However, the advent of chimeric antigen receptor (CAR) T-cell therapies has significantly transformed the treatment landscape for relapsed or refractory multiple myeloma (RRMM). With the emergence of two promising CAR T-cell agents, this study presents the first large, real-world, propensity score-matched comparison between Ide-cel and Cilta-cel with RRMM who have received ≥4 lines of therapy, providing critical insights into their efficacy and safety in clinical practice in the real-world setting.

Methods: This multicenter retrospective cohort study included patients with a diagnosis of RRMM in the TriNetX Network, which is a global research database with 89 healthcare organizations in total providing de-identified patient information. In this analysis, two cohorts were created: the Ide-cel group (with 439 patients) and the Cilta-cel group (with 172 patients). The survival probability, risk of cytokine release syndrome (CRS), and neurotoxicity were assessed before and after propensity score matching. The outcomes were assessed from the initiation of CAR T-cell therapy up to a span of three years. We matched patients based on 52 unique characteristics including demographics, labs, previous chemotherapy, and transplant, resulting in 75 PSM patients per cohort. Analysis methods included measures of association, number of instances, and Kaplan-Meier survival estimates, with T-test statistics assessing differences between cohorts.

Results: After propensity score matching, the mean ages in the Ide-cel and Cilta-cel groups were 65.6 and 65.5, respectively, with 72% and 73.3% being white, and 21.3% and 18.7% being black. Despite an initial difference in survival favoring Cilta-cel in the unmatched analysis, the propensity score-matched analysis found no statistically significant difference in overall survival probabilities between Ide-cel (85.3%) and Cilta-cel (86.7%) after adjusting for confounding variables (risk difference: 0.013, 95% CI: -0.098 to 0.124, p = 0.814).

In the Ide-cel group, 30.7% developed CRS compared to 32% in the Cilta-cel group (risk difference: -0.013, 95% CI: -0.162 to 0.135, p = 0.860), with no difference in survival probability between the two groups. Neurotoxicity occurred in 14.6% of the Ide-cel group compared to 18.6% of the Cilta-cel group, with no statistically significant difference between the groups (risk difference: -0.040, 95% CI: -0.159 to 0.079, p = 0.511).

Relapse rates were 51.3% in the Ide-cel group and 47.4% in the Cilta-cel group, with no statistically significant difference between the two groups in the risk of relapse (risk difference: 3.8, 95% CI: -11.8 to 19.5, p = 0.63). The 3-year survival probabilities were 35.1% for Ide-cel and 37.2% for Cilta-cel respectively for patients who relapsed, with no difference between the two groups (Hazards Ratio: 1.1, 95% CI: 0.739, 1.8, p = 0.86).

Conclusion: In conclusion, our study comparing Ide-cel and Cilta-cel for RRMM demonstrates that, when accounting for confounding variables, Ide-cel and Cilta-cel exhibit comparable efficacy and safety profiles. The initial survival advantage observed for Cilta-cel in the unmatched analysis likely resulted from confounding factors rather than intrinsic superiority. Both treatments exhibited similar safety profiles, including comparable rates of cytokine release syndrome (CRS) and neurotoxicity. The relapse rates and 3-year survival probabilities post-relapse was similar, indicating no significant difference. These findings underscore the importance of adjusting for confounding variables in comparative effectiveness research and provide valuable insights for clinicians in selecting appropriate treatments. These findings support the long-term efficacy of both therapies, providing reassurance to clinicians and patients.