CLOX and neurotox: Utility of the clock drawing task in monitoring for immune effector cell-associated neurotoxicity syndrome following chimeric antigen receptor T-cell therapy.

Immune effector cell-associated neurotoxicity syndrome (ICANS)-associated cognitive impairment is common in patients who receive chimeric antigen receptor T-cell (CAR-T) therapy. This study evaluated the utility of the clock drawing task (CDT) in detecting ICANS in patients with haematological cancers following CAR-T therapy. Data were collected from CAR-T patients at The Alfred Hospital, Melbourne, Australia. Patients underwent frequent assessments using the immune effector cell-associated encephalopathy (ICE) score and the CDT, scored using a modified CLOX (CLOX-M) rating scale, during their admission. We retrospectively reviewed the medical records of consecutive patients who received CAR-T therapy between September 2022 and February 2024 to assess for ICANS and changes in ICE score and CLOX-M. A total of 1208 clock drawings were time matched within an hour of an ICE score for 54 patients (39% female, 64.36 ± 13.25 years). Fourteen (26%) patients developed ICANS. Change in CLOX-M scores from baseline and ICE scores was significantly correlated (ρ = 0.34, p < 0.001). Receiver operating characteristic (ROC) analysis demonstrated that the CLOX-M score has moderate discriminatory power (Area Under the Curve [AUC] = 0.737). A decrease in CLOX-M score of 2 or more had high specificity (0.994) but low sensitivity (0.263) for detecting ICANS. The CDT can be used to complement the ICE score to improve ICANS monitoring.