Cognitive Recovery Following Immune Effector Cell-Associated Neurotoxicity Syndrome in the First 6 Months after Chimeric Antigen Receptor T-Cell Therapy.

Chimeric antigen receptor T-cell (CAR-T) therapy is associated with immune effector cell-associated neurotoxicity syndrome (ICANS), which can manifest as acute and sub-acute cognitive dysfunction. Few studies have investigated cognitive recovery post-CAR-T therapy. In this prospective longitudinal study, patients treated with CAR-T therapy at The Alfred Hospital, Melbourne, underwent cognitive testing at preinfusion and 3- and 6-months postinfusion. Psychometric tests measured attention, processing speed, visuospatial function, language, memory, and executive function. 197 cognitive evaluations were conducted on 91 participants (62% male, mean age at infusion was 66.1 yr [SD = 10.6 yr]). Thirty-two (35%) patients developed ICANS. General linear mixed-effects models found no evidence for an interaction between time and ICANS group for most psychometric test Z-scores, except for a single test of visuospatial function (P = .007). Patients in the ICANS group demonstrated a decline on this test relative to the non-ICANS group, but the magnitude of this effect was small. Patients who develop ICANS demonstrate no strong evidence of significant cognitive decline in 6 months post-CAR-T therapy. Our data are reassuring, revealing that ICANS-related cognitive impairment resolves sometime in the first 3 months post-CAR-T therapy in most cases.