Kye Ling Wong, Lawrence Cheng Kiat Ng, Nicole-Ann Lim, Francesca Lim, Shin Yeu Ong, Tertius Tuy, Chieh Hwee Ang, Michelle Limei Poon, Esther Chan, Victor Ling, Wee Lee Chan, Edwin Thong, Rachel Ng, Hiu Kwan To, Chandramouli Nagarajan, William Hwang, Aloysius Ho, Yunxin Chen
Combining CIRS, Severe4, and CTCI 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.
BACKGROUND: Appropriate patient selection for chimeric antigen receptor T-cell (CAR-T) therapy is essential to minimise preventable adverse outcomes and optimize resource allocation.
OBJECTIVE: 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.
STUDY DESIGN: Eighty patients with relapsed diffuse large B cell lymphoma treated with CAR-T therapy between 2020-2025 were retrospectively reviewed. Outcomes included overall survival (OS), progression free survival (PFS) and severe treatment-related complications, defined as Grade ≥3 cytokine release syndrome (CRS), immune-effector cell-associated neurotoxicity syndrome (ICANS) or immune effector cell-associated haematotoxicity (ICAHT). Patients' fitness and comorbidities were assessed using eastern cooperative oncology group (ECOG), Karnofsky, Cumulative Illness Rating Scale (CIRS), Severe4 and Cellular Therapy Comorbidity Index (CTCI) scores and categorized to either "fit", "borderline" or "unfit".
RESULTS: Using individual comorbidities scores, 30% (n=24) had CIRS ≥7, 8.8% (n=7) had Severe4, and 5% (n=4) had CTCI >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-year OS among the fit, borderline and unfit groups (96.7%, 95% CI 90.5-100; 66.7%, 95% CI 47.3-94.1; 45.8%, 95% CI 22.2-94.8 respectively; p=0.03). A corresponding difference in 1-year PFS was also noted (fit: 78.1%, 95% CI 65.7-92.9; borderline-fit: 52.9%, 95% CI 35.1-79.6; unfit: 43.8%, 95% CI 22.1-86.8; p<0.01).
CONCLUSION: Combining CIRS, Severe4, and CTCI 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.