CAR-FIT: Chimeric Antigen Receptor T-Cell Fitness Index for Therapy-Integrating Comorbidity and Geriatric Assessments to Guide Safe and Equitable Delivery of Chimeric Antigen Receptor T-Cell in Patients with Borderline Physiological Reserve

Appropriate patient selection for chimeric antigen receptor T-cell (CAR-T) therapy is essential to minimize preventable adverse outcomes and optimize resource allocation. We propose a CAR-T fitness index (CAR-FIT) that integrates frailty and comorbidity assessments derived from a real-world cohort to enable objective stratification of patients. Eighty patients with relapsed diffuse large B-cell lymphoma treated with CAR-T therapy between 2020 and 2025 were retrospectively reviewed. Outcomes included overall survival (OS), progression-free survival (PFS), and severe treatment-related complications, defined as grade ≥3 cytokine release syndrome, immune-effector cell-associated neurotoxicity syndrome, or immune-effector cell-associated hematotoxicity. Patients' fitness and comorbidities were assessed using Eastern Cooperative Oncology Group, Karnofsky, Cumulative Illness Rating Scale (CIRS), Severe4, and Cellular Therapy Comorbidity Index (CT-CI) scores and categorized to either "fit," "borderline," or "unfit." Using individual comorbidities scores, 30% (n = 24) had CIRS ≥7, 8.8% (n = 7) had Severe4, and 5% (n = 4) had CT-CI >3. With CAR-FIT, patients were fit (51.2%, n = 41), borderline-fit (28.8%, n = 23), and unfit (20%, n = 16). There was a significant difference in 1-yr OS among the fit, borderline and unfit groups (96.7%, 95% confidence interval [CI] 90.5 to 100; 66.7%, 95% CI 47.3 to 94.1; 45.8%, 95% CI 22.2 to 94.8 respectively; P = .03). A corresponding difference in 1-yr PFS was also noted (fit: 78.1%, 95% CI 65.7 to 92.9; borderline-fit: 52.9%, 95% CI 35.1 to 79.6; unfit: 43.8%, 95% CI 22.1 to 86.8; P < .01). Combining CIRS, Severe4, and CT-CI scores correlated with good outcome stratification. When integrated with frailty assessment, this approach can refine patient selection to allow safer access to potentially eligible candidates.