Efficacy and safety of frail patients treated with ciltacabtagene autoleucel in the real world: A Center for International Blood and Marrow Transplant Research analysis
Menée à partir de données de vie réelle portant sur 541 patients américains présentant des fragilités et atteints d'un myélome multiple réfractaire ou récidivant, cette étude évalue l'efficacité, du point de vue du taux de réponse globale, et la toxicité du ciltacabtagène autoleucel
Background: Ciltacabtagene autoleucel (cilta-cel), an anti–B-cell maturation antigen (BCMA) chimeric antigen receptor T-cell (CAR-T) therapy, is approved for relapsed/refractory multiple myeloma (RRMM).
Methods: Using the Center for International Blood and Marrow Transplant Research registry, this study evaluated outcomes of frail patients receiving commercial cilta-cel from March 2022 to December 2023. Frailty was defined by an adapted simplified score incorporating age, performance status, and comorbidities.
Results: Among 541 patients with available frailty status, 183 (33.8%) were frail and 358 (66.2%) were nonfrail. Overall response rates were comparable (frail 82.8% vs. nonfrail 88.5%). However, frail patients had inferior progression-free survival (PFS) (12-month PFS, 62.7% [95% confidence interval (CI), 53.6%–71.3%] vs. 75.9% [95% CI, 70.4%–81.1%]; p < .01) and overall survival (OS) (12-month OS 72.8% [95% CI, 64.9%–80.0%] vs. 90.4% [95% CI, 86.6%–93.7%]; p < .01). Twelve-month treatment-related mortality in frail patients was 6.8% (95% CI, 3.4%–11.2%) versus 3.6% (95% CI, 1.8%–6.1%), p = .12. Cytokine release syndrome (grade ≥2) occurred in 22.4% of frail versus 17.9% of nonfrail patients (p = .05), and immune effector cell–associated neurotoxicity (ICANS) of any grade was reported in 32.2% versus 17.6% (p < .01). Rates of cranial nerve palsies and Parkinsonism were comparable. Prolonged cytopenia (>day 30) was more common in frail patients (30.6% vs. 21.2%; p < .01). On multivariable analysis, frailty independently predicted worse PFS (hazard ratio [HR], 1.67; 95% CI, 1.16–2.40), OS (HR, 2.46; 95% CI, 1.57–3.87), and higher odds of any-grade ICANS (odds ratio, 2.01; 95% CI, 1.32–3.08) (all p < .01).
Conclusions: Cilta-cel remains effective in frail RRMM, but frailty is associated with reduced survival and increased toxicity, supporting tailored CAR-T strategies.
Cancer , article en libre accès, 2026