Persistent Cognitive Dysfunction After Chimeric Antigen Receptor T-Cell Therapy in Adolescents and Young Adults

Chimeric antigen receptor T-cell (CAR-T) therapy for hematological malignancies causes a neurological complication known as immune effector cell-associated neurotoxicity syndrome (ICANS). The precise neurocognitive pathology underlying ICANS remains incompletely described. The aim of this study is to elucidate that persistent cognitive dysfunction as potential neurotoxicity of CAR-T therapy.

This was a single-center consecutive study of ICANS caused by CAR-T therapy for B-cell acute lymphoblastic leukemia. We determined the cognitive functions of all patients with ICANS at the onset of ICANS symptoms and followed them up in the neurology department thereafter.

Among the 10 CAR-T cases between 2020 and 2022, three patients had ICANS. None of the patients experienced seizures. Of the three patients, the preadolescent patient showed decreased levels of consciousness, tremors, and striatal signs without cognitive dysfunction. The other two adolescent and young adult patients presented with cognitive decline, short- and long-term memory loss, and emotional disturbances. Although the Immune Effector Cell-Associated Encephalopathy score remained low, the cognitive impairment was profound and disabling in both cases. The neurological status of all patients fully recovered to pre-CAR-T status within one month.

The findings in our cases indicate that persistent cognitive dysfunction may be a potentially under-recognized outcome of neurotoxicity due to CAR-T therapy for B-cell acute lymphoblastic leukemia in adolescents and young adults. Detailed neuropsychologic assessments may be beneficial for CAR-T therapy.