Pre-infusion quantitative EEG features associated with delayed neurocognitive impairment following CAR T-cell therapy

Immune effector cell-associated neurotoxicity syndrome (ICANS) is a frequent and potentially severe complication of chimeric antigen receptor (CAR) T-cell therapy, reflecting complex interactions between the immune system and the central nervous system. Reliable baseline biomarkers capable of identifying patients at increased risk of late post-infusion neurological impairment within the first 10 days after CAR T-cell therapy remain limited. We conducted a prospective single-center study to evaluate whether pre-infusion quantitative electroencephalography (qEEG) features are associated with subsequent neurological impairment following CAR T-cell therapy. Fifteen adults with relapsed or refractory lymphomas underwent baseline EEG recordings 2-5 days before infusion. Quantitative analyses included relative spectral power, slow-to-fast frequency ratios, interhemispheric symmetry, and coherence. Supervised classification models were used as exploratory analyses to assess the association between baseline qEEG parameters and neurological outcomes during early (≤5 days) and late (>5 days) post-infusion phases. Baseline qEEG features showed no relevant association with early neurological outcomes. In contrast, pre-infusion increases in delta-to-alpha and delta-to-beta ratios, predominantly in right temporoparietal regions, were associated with later neurological impairment, particularly language disturbances, numerical counting impairment and, less consistently, disorientation and reduced collaboration. Exploratory classification metrics for selected cognitive-language domains were higher than those observed for global ICANS classification or cytokine release syndrome, supporting a possible relative specificity for neurotoxicity-related processes. These findings suggest that baseline qEEG markers of regional cortical slowing may reflect underlying neuroimmune vulnerability and may be associated with later neurocognitive impairment after CAR T-cell therapy. Quantitative EEG may therefore contribute to early risk stratification and neuroimmunological monitoring strategies in patients undergoing immune effector cell therapies.