EEG as a predictive biomarker of neurotoxicity in anti-CD19 CAR T-cell therapy

Objective: Immune effector cell-associated neurotoxicity syndrome (ICANS) is a potentially fatal complication of CD19-directed CAR T-cell therapy. The aim of this study was to investigate the role of EEG as a predictive biomarker of ICANS. Methods: In this prospective, monocentric, cohort study, consecutive refractory B-cell non-Hodgkin lymphoma patients undergoing CAR T-cell therapy had EEG assessments at fixed time points pre- and post-infusion. The risk of ICANS was evaluated according to EEG findings detected qualitatively, using a grading scale ranging from 0 (normal) to 3 (severely abnormal), and quantitatively, using power spectral and connectivity measures. Results: 307 EEGs from 68 patients have been qualitatively evaluated, of whom 238 were eligible for quantitative analysis. Neurotoxicity manifested in 22/68 (32.4%) patients. Pre-infusion EEG abnormalities (grade 1 and 2) were qualitatively detected in 8/68 (11.7%) patients, emerging as a risk factor for ICANS [HR 5.8 (95%CI 2.6–12.9)]. Quantitative analysis of pre-infusion EEGs did not yield significative results. Post-infusion qualitative EEG abnormalities were associated to a higher risk of ICANS development [HR 11.6 (4.4–30.5) for grade 2; HR 9.7 (2.6–36.6) for grade 3]. Concerning the quantitative analysis, in post-infusion EEGs higher theta energy [HR 1.10 (1.03–1.16)] and delta + theta/alfa ratio [HR 1.37 (1.11–1.67)] were associated to higher risk of ICANS, while higher beta energy resulted protective [HR 0.91 (0.85–0.97)]. Conclusions: Our study establishes EEG as a predictive tool for identifying patients at risk for ICANS before CAR T-cell infusion, who may benefit from prophylactic treatments, and anticipating ICANS onset following infusion, enabling early intervention.