Description of neurotoxicity in a series of patients treated with CAR T-cell therapy.

Chimeric antigen receptor-modified T (CAR T) cell therapy is a highly promising treatment for haematological malignancies but is frequently associated with cytokine release syndrome and neurotoxicity. Between July 2018 and July 2019, all patients treated with CD19-targeted CAR T-cell therapy for relapsing lymphoma were followed-up longitudinally to describe neurological symptoms and their evolution over time. Four different French centres participated and 84 patients (median age 59 years, 31% females) were included. Neurotoxicity, defined as the presence of at least one neurological symptom appearing after treatment infusion, was reported in 43% of the patients. The median time to onset was 7 days after infusion with a median duration of 6 days. More than half of the patients (64%) had grade 1-2 severity and 34% had grade 3-4. CRS was observed in 80% of all patients. The most frequent neurological symptoms were cognitive signs, being severe in 36%, and were equally distributed between language disorders and cognitive disorders without language impairment. Non-pyramidal motor disorders, severe in 11%, were reported in 42% of the patients. Elevation of C-reactive protein (CRP) within 4 days after treatment was significantly correlated with the occurrence of grade 3-4 neurotoxicity. Although sometimes severe, neurotoxicity was almost always reversible. The efficacy of steroids and antiepileptic drugs remains unproven in the management of neurotoxicity. Neurotoxicity associated with CAR T-cell therapies occurs in more than 40% of patients. The clinical pattern is heterogeneous but cognitive disorders (not limited to language disorders) and, to a minor degree, non-pyramidal motor disorders, appeared as a signature of severe neurotoxicity.