Identifying Predictors of NRM After CAR T-Cell Therapy
Barone A, Stella F, Ljevar S, et al. Systemic Inflammation and CAR-T Specific Toxicities as Major Drivers of Non-Relapse Mortality: Analysis from the Italian Prospective Observational CART-SIE Study. Transplantation and Cellular Therapy. 2026; (doi: 10.1016/j.jtct.2026.02.048).
Clinical study evidence indicates that toxic effects and infections associated with chimeric antigen receptor (CAR) T-cell therapy are leading contributors to non-relapse mortality (NRM) in lymphoma patients after CAR T-cell infusion. The conclusion is based on observations for 932 trial participants who received CAR T-cell therapy from 2019 to 2025. Of 305 deaths occurring over a median follow-up of 17.8 months, 47 (5%) were directly attributable to NRM. Infections were the primary cause of NRM, accounting for 51% of all cases, with cytokine release syndrome (CRS), immune effector cell-associated syndrome (ICANS), and other CAR T-cell–related acute toxicities accounting for 30%, and secondary malignancies representing 11%. While these toxicities were robust post-infusion predictors of NRM, diabetes and elevated ferritin levels were the only pre-infusion predictors. The findings underscore how host-specific factors and systemic inflammation influence CAR T outcomes, and they reinforce the importance of multidisciplinary care in CAR T-cell therapy. To preserve the long-term benefits of the immunotherapy, mitigate NRM, and promote long-term survival, the authors highlight the need for optimized patient selection, aggressive management of acute toxicities, individualized prophylaxis against infections, and proactive long-term oncologic monitoring.