Aim to evaluate the prevalence of neurotoxicity and associated neurological events in patients undergoing CAR T-cell therapy. 

Chimeric antigen receptor (CAR) T-cell therapy has revolutionized the treatment of hematological malignancies, offering durable remissions for patients with incurable diseases. However, one of the most concerning side effects is neurological events, from mild cognitive impairment to severe encephalopathy.

We performed a systematic review and meta-analysis following PRISMA guidelines, retrieving data from PubMed, Embase, and Cochrane databases. We included randomized clinical trials that compare patients who presented any hematological malignancy treated with CAR T-cell therapy. Our primary endpoint was immune effector cell–associated neurotoxicity syndrome (ICANS). Secondary outcomes included neurotoxicity, cytokine release syndrome (CRS), and any neurological events (ANE). We pooled event prevalence for single-arm analyses. A random-effects model was used to calculate the proportions with 95% confidence intervals (CIs). 

Six randomized clinical trials were selected. A subgroup analysis assigned the same histological cancer was used to assess prevalence between groups. A total of patients were analyzed. ICAN was assessed in 622 patients of whom 71 presented any grade with a proportion of 0.16 [0.00; 0.36], 0.24 [0.00; 0.69] in the B cell lymphoma, and 0.10 [0.00; 0.20] in the Multiple myeloma group. Neurotoxicity was assessed in 622 patients, being presented in 84 patients with a proportion of 0.14 [0.04; 0.23]. In 884 patients, 365 presented any neurological events with a proportion of 0.39 [0.18; 0.59]. Of 884 patients, 583 presented CRS with a proportion of 0.61 [0.37; 0.85], in the Multiple myeloma group, a higher proportion was shown with 0.82 [0.71; 0.93]. 

Our study shows that ICAN is an important neurological adverse event and is highly prevalent in B-cell lymphoma. Other neurological events are shown to be highly prevalent, addressing the need to investigate adjunctive therapy to minimize its effects.