Differences in Ide-cel and Cilta-cel Outcomes Call for Personalized RRMM Treatment

In the treatment of relapsed or refractory multiple myeloma (RRMM), the difference in the efficacy and safety of available B-cell maturation antigen (BCMA)–directed chimeric antigen receptor (CAR) T-cell therapies has been an important question.

BCMA–directed CAR T-cell therapies were a vital advancement for the treatment of RRMM. The introductions of agents such as idecabtagene vicleucel (ide-cel) and ciltacabtagene autoleucel (cilta-cel) to the market in 2021 and 2022 ultimately changed the standard of care. According to new research, cilta-cel outperforms ide-cel in terms of both efficacy and safety.¹

“Cilta-cel demonstrates superior treatment responses compared to ide-cel, particularly in terms of depth of response, progression-free survival [PFS], and overall survival [OS]. However, this enhanced efficacy comes with a higher incidence of certain toxicities, including grade 3 or higher cytokine release syndrome [CRS], although the overall incidence remains low for both therapies, as well as infections and delayed non-ICANS [immune effector cell–associated neurotoxicity syndrome] neurotoxicities, lead investigator Doris K. Hansen, MD, assistant member, Moffitt Cancer Center told Blood Cancers Today.

The study included 641 patients who underwent leukapheresis, with 386 receiving ide-cel and 255 receiving cilta-cel.² Of these, 586 patients proceeded to infusion (350 with ide-cel and 236 with cilta-cel), with median follow-up durations of 12.6 months and 13.0 months, respectively. After inverse probability of treatment weighting was applied, patient characteristics were well balanced, ensuring a robust comparison between the 2 therapies.

Cilta-cel demonstrated a superior efficacy profile, with patients achieving higher rates of complete response or better (odds ratio [OR], 2.42; 95% CI, 1.63-3.60). In addition, cilta-cel was associated with longer PFS (hazard ratio [HR], 0.48; 95% CI, 0.36-0.63) and OS (HR, 0.67; 95% CI, 0.46-0.97), reinforcing its effectiveness in prolonging patient outcomes. These findings suggest that cilta-cel may offer a more durable treatment response compared with ide-cel.²

“While cilta-cel demonstrates improved efficacy, it is associated with a higher incidence of certain toxicities compared to ide-cel, in heavily pretreated patients who have received 4 or more prior lines of therapy. These findings offer critical insights into the efficacy and safety profiles of both therapies, providing valuable information for patient counseling and guiding the selection of CAR T-cell therapy for specific patient populations,” said Dr. Hansen.

Patients treated with cilta-cel experienced significantly increased rates of grade 3 or higher CRS (OR, 6.80; 95% CI, 2.28-20.33) and infections (OR, 2.03; 95% CI, 1.41-2.92). Delayed neurotoxicity was also notably more common with cilta-cel (OR, 20.07; 95% CI, 4.46-90.20), highlighting the need for close neurologic monitoring of patients receiving this therapy.

Despite these risks, no significant differences were observed between ide-cel and cilta-cel regarding the incidence of ICANS, any-grade CRS, severe cytopenia at days 30 and 90, or nonrelapse mortality. This suggests that although cilta-cel presents a heightened risk for certain complications, its overall safety profile remains comparable to that of ide-cel in key areas.

When restricting the analysis to patients infused after March 2022—the period following cilta-cel’s FDA approval—results remained consistent, further validating the observed trends. Given cilta-cel’s demonstrated advantages in treatment response and survival outcomes, it may represent a preferred choice for patients eligible for BCMA-directed CAR T-cell therapy, provided that adverse event risks are carefully managed.

“It is important to consider patient comorbidities and preferences when selecting treatment options. By informing more personalized treatment decisions, these findings have the potential to optimize patient outcomes and support clinical decision-making,” Dr. Hansen stated.

Hansen and colleagues² concluded that future research will be critical to further optimizing CAR T-cell therapy strategies and improving long-term outcomes for patients with RRMM.

References

1. Peery MR, Hill H, Sharps A, Zaver A, Moore DC. B-cell maturation antigen-directed immunotherapies for the treatment of relapsed/refractory multiple myeloma: a review of the literature and implications for clinical practice. Ann Pharmacother. 2024 Oct 7:10600280241282115. doi:10.1177/10600280241282115
2. Hansen DK, Peres LC, Dima D, et al. Comparison of standard-of-care idecabtagene vicleucel and ciltacabtagene autoleucel in relapsed/refractory multiple myeloma. J Clin Oncol. 2025 Feb 18:JCO2401730. doi:1200/JCO-24-01730