Efficacy and safety of frail patients treated with ciltacabtagene autoleucel in the real world: A Center for International Blood and Marrow Transplant Research analysis.
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).
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.
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).
Cilta-cel remains effective in frail RRMM, but frailty is associated with reduced survival and increased toxicity, supporting tailored CAR-T strategies.
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.
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).
Cilta-cel remains effective in frail RRMM, but frailty is associated with reduced survival and increased toxicity, supporting tailored CAR-T strategies.
Authors
Mian Mian, Faisal Faisal, Chen Chen, Brazauskas Brazauskas, Oloyede Oloyede, Ahmed Ahmed, Afrough Afrough, Anderson Anderson, Banerjee Banerjee, Berdeja Berdeja, Bidikian Bidikian, Devos Devos, Dhakal Dhakal, Dias Dias, Dima Dima, Efebera Efebera, Gowda Gowda, Hansen Hansen, Hashmi Hashmi, Landau Landau, Lekakis Lekakis, Mirza Mirza, Narra Narra, Patel Patel, Rosko Rosko, Schroeder Schroeder, Sidana Sidana, Usmani Usmani, Pasquini Pasquini, Nishihori Nishihori, Akhtar Akhtar, Mohan Mohan
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