Ciltacabtagene Autoleucel Demonstrates Superior Progression-Free Survival in Patients With Relapsed, Refractory Multiple Myeloma

Ciltacabtagene autoleucel (cilta-cel, Carvykti; Janssen Biotech, Inc) demonstrated superior outcomes compared with idecabtagene vicleucel (ide-cel, Abecma; Bristol Myers Squibb) in a real-world study of patients with triple-class exposed relapsed, refractory multiple myeloma (RRMM). The data, collected from an international, multicenter cohort study, are the first to provide a direct comparison between the 2 chimeric antigen receptor (CAR) T-cell therapies.

3D rendering of CAR T-cells | Image Credit: © Animager - stock.adobe.com

Multiple myeloma is a challenging, heterogeneous malignancy characterized by periods of remission followed by relapse. With each subsequent line of therapy, treatment responses and overall outcomes typically worsen. Emerging CAR T-cell therapies demonstrate significant efficacy and safety in real-world and clinical settings, underscoring their place in the RRMM treatment paradigm.¹

Cilta-cel and ide-cel are BCMA-directed immunotherapies that were approved by the FDA in 2022 and 2021, respectively, for treatment of adult patients with RRMM who had received 4 or more prior lines of therapy. As of January 2025, they are the only FDA approved BCMA-directed therapies on the market. Both have demonstrated statistically significant efficacy and safety results; however, the real-world cohort analysis suggests the superiority of cilta-cel over ide-cel, with meaningful improvements in overall response rate (ORR) and progression-free survival (PFS).^1,2

The researchers evaluated and compared the outcomes of patients with RRMM receiving either ide-cel (n=162) or cilta-cel (n=42), focusing on co-primary efficacy end points of ORR and PFS. They also included the co-primary safety end points of cytokine release syndrome (CRS) and immune-effector cell-associated neurotoxicity syndrome (ICANS). The median turnaround time between apheresis and infusion was 47 days and 68 days for ide-cel and cilta-cel, respectively, (P < .001).³

Patients receiving cilta-cel achieved a significantly higher ORR (93% vs. 79%; P < .001), with complete response at day 30, of 48% compared with 26% of those receiving ide-cel, according to the data (P < .001). For the cilta-cel arm, the researchers reported a 10-month PFS and overall survival (OS) of 82% and 90%, respectively, compared with 47% (PFS) and 77% (OS) in the ide-cel arm (P < .001 and P = 0.06).³

Instances of CRS and ICANS were similar in each treatment arm (81% and 19% for cilta-cel versus 85% and 19% for ide-cel). Severe grade 3 to 4 CRS and ICANS occurred in 10% and 7% in the cilta-cel arm, respectively. In the ide-cel arm, CRS occurred significantly earlier (median, 2 days vs. 4 days; P < .001). Cilta-cel exhibited a later peak of CAR T-cell expansion at day 14 compared with day 7 for ide-cel, which was associated with ICANS. There were nonrelapse mortalities in 3% of patients receiving cilta-cel and 5% in those receiving ide-cel.³

The cohort study’s findings suggest the potential superior clinical benefits of cilta-cel, supported by real-world evidence. These data provide a deeper understanding of the actual outcomes of cilta-cel and ide-cel CAR T-cell therapies, allowing clinicians to make more informed treatment decisions for patients.

REFERENCES

1. Real-world outcomes show efficacy, safety of ciltacabtagene autoleucel in relapsed, refractory multiple myeloma. Pharmacy Times. December 3, 2024. Accessed January 21, 2025. https://www.pharmacytimes.com/view/study-shows-comparable-safety-efficacy-of-idecabtagene-vicleucel-in-older-patients

2. Study shows comparable safety, efficacy of idecabtagene vicleucel in older patients. Pharmacy Times. December 3, 2024. Accessed January 21, 2025. https://www.pharmacytimes.com/view/study-shows-comparable-safety-efficacy-of-idecabtagene-vicleucel-in-older-patients

3. Merz M, Albici A, Tresckow B, et al. Idecabtagene vicleucel or ciltacabtagene autoleucel for relapsed or refractory multiple myeloma: an international multicenter study. HemaSphere. January 16, 2025. doi:10.1002/hem3.70070