Retrospective Data Show Improved Efficacy but Higher Toxicity With Cilta-Cel vs Ide-Cel in R/R Myeloma

Multiple Myeloma |
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A retrospective analysis comparing standard-of-care idecabtagene vicleucel (ide-cel; Abecma) and ciltacabtagene autoleucel (cilta-cel; Carvykti) demonstrated improved survival outcomes but increased toxicity with cilta-cel in patients with relapsed/refractory multiple myeloma.

Findings from the multicenter chart review published in the Journal of Clinical Oncology showed that cilta-cel was associated with a significantly higher likelihood of grade 3 or higher cytokine release syndrome (CRS) compared with ide-cel (5% vs 2%; odds ratio [OR], 6.80; 95% CI, 2.28-20.33), infections (47% vs 35%; OR, 2.03; 95% CI, 1.41-2.92), and delayed neurotoxicity (10% vs 0.6%; OR, 20.07; 95% CI, 4.46-90.20).

However, there was no association with increased risk of any-grade CRS, any-grade immune effector cell–associated neurotoxicity syndrome (ICANS), or severe ICANS. The incidence of any-grade CRS was 74% with cilta-cel vs 84% with ide-cel.

“Encouragingly, severe CRS rates remained relatively low in both treatment cohorts, consistent with clinical trial data, despite a significant proportion of patients having comorbidities that would have made them trial-ineligible,” lead study author Doris K. Hansen, MD, and colleagues wrote in the publication. Hansen is an assistant member in the Department of Blood and Marrow Transplant and Cellular Immunotherapy at Moffitt Cancer Center in Tampa, Florida.

Patients treated with cilta-cel were more likely to experience any second primary malignancies (SPMs; OR, 1.77; 95% CI, 0.89-3.56) and SPMs excluding nonmelanoma skin cancers (OR, 1.72; 95% CI, 0.74-3.97; P = .2); however, these associations were not statistically significant. Notably, there was no association with an increased risk of hematologic SPMs in patients treated with cilta-cel.

Regarding efficacy, patients treated with cilta-cel were more likely to have a best response of complete response or better, as well as partial response or better (OR, 2.42; 95% CI, 1.63-3.60). Cilta-cel was also associated with a statistically significant improvement in progression-free survival (HR, 0.48; 95% CI, 0.36-0.63) and overall survival (HR, 0.67; 95% CI, 0.46-0.97) compared with those who received ide-cel.

"Cilta-cel demonstrated superior efficacy and survival, with higher incidence of certain toxicities, compared with ide-cel,” study authors wrote.

Study Design

The study utilized a retrospective chart review design to evaluate real-world outcomes in patients with relapsed/refractory multiple myeloma who underwent leukapheresis with the intent to receive standard-of-care ide-cel or cilta-cel at one of 19 participating institutions. Eligible patients were leukapheresed by December 31, 2022.

To account for potential confounding factors and balance baseline characteristics between treatment groups, the investigators employed an inverse probability of treatment weighting approach.

A total of 641 patients underwent leukapheresis to receive ide-cel (n = 386) or cilta-cel (n = 255). Of these, 586 patients were infused with their respective CAR T-cell therapy (ide-cel, n = 350; cilta-cel, n = 236).

The median follow-up duration was 12.6 months for ide-cel and 13.0 months for cilta-cel. Outcomes related to safety, efficacy, and survival were assessed and compared between the two treatment groups.

Baseline Patient Characteristics

The median age at infusion was similar between cohorts: 65 years (range, 36-90) for ide-cel and 64 years (range, 30-84) for cilta-cel. A comparable proportion of patients were male (58% vs 57%, respectively). Most patients identified as non-Hispanic White (70% for ide-cel and 76% for cilta-cel), while the representation of non-Hispanic Black and Hispanic patients was lower across both groups.

High-risk cytogenetics were present in 33% of the ide-cel cohort and 38% of the cilta-cel cohort. Extramedullary disease was reported in 24% of patients receiving ide-cel and 26% of those receiving cilta-cel. Prior exposure to anti-BCMA therapy was low in both groups, at 18% and 14%, respectively. Pentarefractory disease was slightly more common in the ide-cel cohort (35%) than in the cilta-cel cohort (30%).

An ECOG performance status of 0 or 1 was reported in 94% of patients receiving ide-cel and 89% receiving cilta-cel. Bridging therapy was more frequently used in the cilta-cel group (76%) compared with the ide-cel group (72%); a higher proportion achieved partial response or better before infusion in the cilta-cel arm (21% vs 10%).

Reference

Hansen DC, Peres C, Dima D, et al. Comparison of standard-of-care idecabtagene vicleucel and ciltacabtagene autoleucel in relapsed/refractory multiple myeloma. J Clin Oncol. Published online February 18, 2025. doi:10.1200/JCO.24.01730