Cancer. 2026 Oct 1;132(19):e70614. doi: 10.1002/cncr.70614.
ABSTRACT
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.
PMID:42779338 | DOI:10.1002/cncr.70614