Allogeneic CAR-T (National University Hospital)

Cognitive dysfunction is a common manifestation of immune effector cell-associated neurotoxicity syndrome (ICANS) following chimeric-antigen receptor (CAR) T-cell therapy. With CAR-T therapy indications rapidly expanding beyond traditional indications, it has become increasingly important to understand CAR-T therapy-related neurotoxicity and cognitive impairment to optimise treatment safety, and to improve monitoring and management. This study examined the Repeatable Battery of the Assessment of Neuropsychological Status (RBANS) as a tool for monitoring subacute cognitive recovery.

In this prospective, single-centre cohort study, patients undergoing CAR T-cell therapy at The Alfred Hospital in Melbourne were evaluated with the RBANS at Day+1, Day+7, and a subacute outpatient visit (median 45 days post-infusion, IQR: 38 - 52).

238 RBANS administrations were conducted on eighty-seven patients (63% male, mean age of 66.2 years at infusion). Thirty (34%) patients developed ICANS. General linear mixed-effects models found significant time by ICANS group interactions. Post-hoc comparisons revealed that the ICANS group demonstrated significantly worse Attention, Language, and Total Index scores at Day+7, and significantly worse Total Index score at subacute review compared to the no ICANS group. Supplementary analyses also demonstrated that the higher grade (Grades 3 and 4) ICANS group performed worse than low-grade (Grades 1 and 2) and no ICANS groups.

Patients who developed ICANS demonstrated deficits in attention and language. These cognitive deficits may persist for more than 45 days post-infusion in some patients. The RBANS shows potential as a valid measure of ICANS-related cognitive dysfunction, which can be used at the bedside and in clinic, as well as in research settings.