An Electronic Frailty Index Is Associated with Outcomes in Older Adults Receiving CAR-T Therapy

Predicting outcomes for older adults undergoing Chimeric Antigen Receptor T-cell (CAR-T) therapy is critical. Frailty is associated with poor outcomes, but can be difficult to measure in clinical practice. We retrospectively analyzed patients age ≥65 years receiving commercial CAR-T at Mass General Brigham for multiple myeloma and B-cell non-Hodgkin lymphoma. We calculated an electronic frailty index (eFI), a validated, automated frailty score (<0.1=robust, 0.1-0.2=pre-frail, 0.2-0.3=frail, and >0.3=very frail). We evaluated associations of eFI (robust/prefrail vs frail vs very frail) with overall survival (OS), event-free (death, progression, or new treatment) survival (EFS), toxicity (cytokine release syndrome (CRS) and/or immune effector cell-associated neurotoxicity syndrome (ICANS)), and days alive and out of hospital in the first 30 days (DAOH) using regression models controlling for confounders. Among 260 patients (median age: 73 years [range 65-91]), 10% were robust, 25% prefrail, 28% frail, and 37% very frail. In multivariable analyses, being frail was not associated with OS (hazard ratio [HR] 1.22, p=0.45) or EFS (HR=1.39, p=0.14), but very frail patients had significantly worse OS (HR=1.64, p<0.05) and EFS (HR=2.02, p<0.01). Both frail and very frail patients, respectively, had higher odds of grade 3+ toxicity (odds ratio [OR]=3.28, p<0.05; OR=4.84, p<0.01) and fewer DAOH (β= -2.37, p = 0.03; β= -3.79, p<0.01). The eFI identifies frail and very frail patients with higher risk for grade 3+ CRS/ICANS and increased healthcare utilization. Very frail patients are especially high-risk with poor OS and EFS. The eFI holds promise as an automated CAR-T risk-stratification tool.