Abstract
BACKGROUND: Chimeric antigen receptor (CAR) T-cell therapy has revolutionized the treatment of hematological malignancies, offering durable remissions. However, concerns regarding its neurocognitive and psychological impact have emerged, particularly in patients experiencing immune effector cell-associated neurotoxicity syndrome (ICANS). Despite growing clinical use, the long-term effects on cognitive function, psychological well-being, and quality of life (QoL) remain unclear. OBJECTIVE: This systematic review evaluates the neurocognitive, psychological, and QoL outcomes associated with CAR T-cell therapy. METHODS: A systematic search of PubMed, Embase, and Scopus was conducted following PRISMA guidelines. Eligible studies included randomized controlled trials, cohort studies, and observational studies assessing cognitive function, psychological outcomes (anxiety, depression, PTSD), and QoL post-CAR T-cell therapy. Study quality was assessed using the Cochrane Risk of Bias Tool for RCTs and the Newcastle-Ottawa Scale for observational studies. RESULTS: Eighteen studies met the inclusion criteria. Up to 44% of CAR T-cell recipients experienced cognitive impairments, particularly in memory, attention, and executive function. ICANS was reported in 25%-70% of patients, with severe ICANS in 10%-20%. Persistent cognitive deficits were observed beyond 12 months in a subset of patients, particularly those with severe ICANS. Psychological outcomes included anxiety and depression in 35% of patients, with PTSD reported in those experiencing severe neurotoxicity. While QoL improved over time, patients with prolonged neurotoxicity had delayed recovery. EEG-based biomarkers, including the EICANS Score, showed promise in predicting ICANS severity. CONCLUSIONS: CAR T-cell therapy is associated with neurocognitive and psychological sequelae, particularly in patients with severe ICANS. Long-term cognitive monitoring, standardized assessments, and targeted rehabilitation strategies are needed to optimize patient outcomes.