Mania and psychosis following chimeric antigen receptor T-cell therapy: A report of two cases and mechanistic discussion

CD20. CD19-targeted chimeric antigen receptor modified T-cell immunotherapy (CAR T-cell therapy) is an experimental CAR with increasing use for the treatment of lymphoid malignancies. Although acute neuropsychiatric toxicities are well described following CAR T-cell therapies, late-onset persistent neuropsychiatric symptoms, including mania and psychosis, are poorly characterized, and their underlying mechanisms are unknown. Here, we present two cases of new-onset mania and psychosis in the months following dual targeted CD20. CD19 CAR T-cell therapy, contributing significantly to the literature wherein no cases of such have been reported. We discuss the published literature on chronic neuropsychiatric symptoms following CAR T-cell therapy as well as potential neurobiological mechanisms for these effects. Finally, we discuss therapeutic considerations including the potential role of second-generation antipsychotics, such as olanzapine, which may be effective in the treatment of late-onset and persistent neuropsychiatric symptoms, including psychosis, following CAR-T cell treatment.