Prolonged Neurologic Symptoms Following Immune Effector Cell-Associated Neurotoxicity Syndrome in Patients With Large...

While immune effector cell-associated neurotoxicity syndrome (ICANS) is a well-defined adverse effect associated with chimeric antigen receptor-modified T cell (CAR-T) therapy, some patients develop prolonged neurologic symptoms. Few studies have examined characteristics and outcomes of patients who develop such symptoms. The objective of this study was to provide an analysis of patients who developed ICANS in a single-center cohort of patients with large B-cell lymphoma (LBCL) who received commercial CAR-T and compare characteristics and outcomes between patients with vs. without subsequent prolonged neurologic symptoms. We examined a retrospective cohort of patients with LBCL treated with CAR-T at our institution who developed ICANS. Prolonged neurologic symptoms were defined as those lasting longer than four weeks. Thirty three of 278 (12%) LBCL patients treated with commercial CAR-T experienced ICANS. Nine patients (27%) experienced prolonged neurologic symptoms following ICANS, eight with ICANS grade ≥3 (high-grade) and one with ICANS grade <3 (low-grade). There were a range of symptoms experienced by these patients including difficulties with short-term memory, difficulties with long-term memory, aphasia, and tremors. The incidence of prolonged neurologic symptoms was greater in patients experiencing high-grade as compared to low-grade ICANS (42.1% vs. 7.1%, P = .049). However, no other pre-treatment characteristics or post-treatment outcomes were associated with development of prolonged neurologic symptoms following ICANS. In summary, nearly half of all patients with LBCL treated with CAR-T at our institution who developed high-grade ICANS experienced prolonged neurologic symptoms; however, pretreatment characteristics and post-treatment outcomes were not predictive of this clinical condition. Further work is needed to identify patients treated with CAR-T at risk for experiencing prolonged neurologic symptoms and developing strategies for evaluation and treatment of this toxicity.