Predictors of Neurotoxicity in a Large Cohort of Italian Patients Undergoing Anti-CD19 Chimeric Antigen Receptor (CAR) T-Cell Therapy

Background: Anti-CD19 chimeric antigen receptor (CAR) T-cell therapy is an innovative and effective treatment for patients with B-cell hematological malignancies. Despite its high efficacy, it has been associated with the development of acute toxicities that can be severe or even fatal. Indeed, cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) can induce significant morbidity and require close monitoring. Identification of clinical and laboratory markers able to predict the occurrence of ICANS may allow prompt recognition and more effective management strategies. Methods: Here, we report a retrospective study on a cohort of 81 Italian adult patients treated in our hospital between September 2019 and April 2024. We reviewed all clinical, demographic, laboratory, and neurophysiological data in order to identify potential predictors. Results: The results of the multivariate analysis confirmed that ICANS typically occurred less frequently in younger patients, especially when treated with 41BB co-stimulated CAR-T. Baseline EEG abnormalities are confirmed to be a fundamental predictor of neurotoxicity. Interestingly, we identified GammaGT as a new, statistically significant marker of ICANS. This represents a novel finding, probably related to the important role of GammaGT also in neuroinflammation. Conclusions: Our results need to be confirmed in a larger cohort of patients in order to eventually be integrated into current clinical practice and management of patients undergoing CAR-T.