Transplantation and cellular therapy · 2025
Repeatable Battery for the Assessment of Neuropsychological Status: Preliminary Utility for Subacute Cognitive Monitoring after Immune Effector Cell-Associated Neurotoxicity Syndrome after Chimeric Antigen Receptor T-Cell Therapy.
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Kazzi Christina, Griffith Sarah P, Ko Katherine Y, Pearce Daniel J, Wronski Miriam, Seery Nabil, Wesselingh Robb, Tan Tracie H, Simpson Ty, Abbott Cassandra, Li Jian, Cole Elizabeth, Westworth Michael, Inam Shafqat, Rushen Tiffany, Parsons Sriyani, Melitsis Lauren, Wong Shu Min, Butzkueven Helmut, Van Der Walt Anneke, Nandurkar Harshal, Tam Constantine S, Fleming Shaun, O'Brien Terence J, Alpitsis Rubina, Spencer Andrew, Malpas Charles B, Monif Mastura
Аннотация
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 optimize treatment safety and to improve monitoring and management. This study examined the Repeatable Battery for 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 to 52). A total of 238 RBANS administrations were conducted on 87 patients (63% male, mean age of 66.2 yr at infusion). Thirty (34%) patients developed ICANS. General linear mixed-effects models found significant time by ICANS group interactions. Posthoc 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.