Neurotoxicity from chimeric antigen receptor T-cells: an update on diagnosis and treatment

Abstract

Purpose of review: Chimeric antigen receptor (CAR) T-cell therapies are increasingly used in hematologic malignancies and are now being investigated in autoimmune disorders. This review aims to summarize the spectrum of neurological complications associated with CAR-T.

Recent findings: While early-onset neurotoxicity is well characterized, other neurological syndromes are increasingly reported. Neurological complications can be provisionally classified into three categories: early-onset immune effector cell-associated neurotoxicity syndrome (ICANS); delayed-onset neurological syndromes specific to single CAR T-cell types; and tumour inflammation-associated neurotoxicity (TIAN). Other postinfusion neurological syndromes have also been observed but with uncertain links to CAR T-cells. Management must be tailored to preserve both neurological function and CAR T-cell efficacy. Ongoing efforts target biomarker development, and risk-adapted strategies, especially in steroid-refractory cases.

Summary: As CAR T-cell indications broaden, clinicians must recognize diverse neurological toxicities and implement individualized, evidence-based interventions to improve neurological outcomes.

Keywords: chimeric antigen receptor T-cell therapy; immune effector cell-associated neurotoxicity syndrome; movement and neurocognitive toxicities; neurotoxicity; tumor inflammation-associated neurotoxicity.