Comparative Efficacy and Safety of Ciltacabtagene Autoleucel and Idecabtagene Vicleucel in Real-World Relapsed/Refractory Multiple Myeloma: A Retrospective Intention-to-Treat Analysis
Authors: Amoozgar Behzad , Bangolo Ayrton I , Vesole David H. , Siegel David S. , Biran Noa , Phull Pooja , Donato Michele L. , Parmar Harsh 
Published: December 2024

Introduction

Chimeric Antigen Receptor T-cell (CAR-T) therapy has emerged as a major advancement in the therapeutic landscape for relapsed/refractory multiple myeloma (R/R MM). Carvykti (ciltacabtagene autoleucel) and Abecma (idecabtagene vicleucel), both targeting B-cell maturation antigen (BCMA), have shown promising results in clinical trials. However, real-world comparative data remains limited. This study aims to compare the clinical outcomes and safety profiles of Carvykti and Abecma in R/R MM patients outside of controlled clinical trial settings.

Methods

A retrospective cohort study was conducted at John Theurer Cancer Center, including R/R MM patients who underwent CAR-T therapy from January 2018 to December 2023. Adult patients (18-70 years) were identified through our institutional database. Data collection included baseline characteristics, treatment history, response to therapy, and adverse events. Safety outcomes were assessed using CTCAE v5.0, with cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) graded per ASTCT criteria. Efficacy outcomes included overall response rates (ORR), progression-free survival (PFS), and overall survival (OS). An intention-to-treat (ITT) analysis was performed, including patients who underwent apheresis regardless of subsequent CAR-T infusion. Survival analyses were conducted using the Kaplan-Meier method, with PFS and OS calculated from the date of apheresis. Cox proportional hazards models were used to calculate hazard ratios (HR) and 95% confidence intervals (CI) for prognostic factors in univariate and multivariate analyses.

Results

A total of 114 patients were included in this study (Abecma: n=50, Carvykti: n=64). The median age was significantly different between groups (Abecma: 72.8 years, Carvykti: 65.3 years; p=0.001). Median prior lines of therapy were similar (Abecma: 5, Carvykti: 6; p=0.12). Of 101 patients with evaluable FISH data, high-risk FISH was comparable (Abecma: 51.2%, Carvykti: 51.7%; p=0.96). Extramedullary disease (EM) was present in 23.5% (12/51) of Abecma and 17.5% (11/63) of Carvykti patients (p=0.42). Median vein-to-vein time was shorter for Abecma (47 vs. 55 days; p&lt;0.001). Apheresis failure rates were similar (Abecma: 11.8% [6/51], Carvykti: 9.4% [6/64]; p=0.67).

In the ITT analysis, the overall response rate (ORR) was significantly higher in the Carvykti group compared to Abecma (86% [49/57] vs. 60% [30/51], p=0.002). The median PFS was significantly longer for Carvykti (not reached vs. 7.5 months; p&lt;0.0001). OS was not reached in either group (p=0.12). Per-protocol analysis showed similar trends.

EM disease was associated with inferior PFS (ITT: 4.1 vs. 21.4 months; p&lt;0.0001) and OS (ITT: 6.2 months vs. not reached; p&lt;0.0001). Univariate analysis identified Carvykti treatment (HR 0.28, 95% CI 0.14-0.54; p&lt;0.001) as a favorable prognostic factor and the presence of EM disease (HR 4.3, 95% CI 2.3-7.9; p&lt;0.001) as unfavorable.

Safety profiles were comparable between groups. Any-grade CRS occurred in 82.2% (37/45) of Abecma and 67.2% (39/58) of Carvykti patients (p=0.08), with grade III or higher CRS in 2.2% (1/45) and 0% (0/58), respectively (p=0.2). Any-grade ICANS was observed in 11.1% (5/45) of Abecma and 12.1% (7/58) of Carvykti patients (p=0.8), with grade III or higher ICANS in 2.2% (1/45) and 3.5% (2/58), respectively (p=0.7).

Conclusion

In this real-world analysis of R/R MM patients, Carvykti demonstrated superior efficacy with significantly higher ORR and longer PFS compared to Abecma, despite differences in baseline characteristics. EM disease emerged as a significant negative prognostic factor for both PFS and OS. Safety profiles were similar between the two CAR-T products, with manageable rates of CRS and ICANS. These findings provide valuable insights into the comparative effectiveness and safety of BCMA-targeted CAR-T therapies outside clinical trial settings and highlight the need for improved strategies for patients with extramedullary disease. Further studies are warranted to confirm these results and explore potential mechanisms underlying the observed differences in outcomes.