Baseline Cognitive and Neurological Status Does Not Modify the Occurrence of ICANS in CAR T‐Cell Therapy for Aggressive B‐Cell Lymphoma

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BACKGROUND: Immune effector cell-associated neurotoxicity syndrome (ICANS) is a common, serious complication of CAR T-cell therapy for blood cancers. This study evaluates the impact of baseline cognitive status and pre-existing neurological injury on the occurrence of ICANS. METHODS: We conducted a prospective study of adult patients treated with CAR T-cell therapy for aggressive B-cell lymphoma at our centre between May 2020 and December 2023. All patients underwent neurological examination, cerebral MRI and cognitive assessment measured by the Montreal Cognitive Assessment (MoCA). We measured total metabolic tumour volume (TMTV), lactate dehydrogenase (LDH), albumin, ferritin and C-reactive protein (CRP) before CART cell infusion, and serum neurofilament light chain (NfL) levels. We evaluated the impact of these factors on ICANS occurrence using multivariate analysis. RESULTS: Among the 156 adult patients treated with CAR T-cell therapy, 32.7% developed ICANS. The median MoCA score at baseline was 26 [IQR 24; 28]. There was no significant association between the onset of ICANS and baseline cognitive performance (p 0.57). MoCA scores did not differ by ICANS grade. Pre-existing neurological injury were not associated with increased ICANS risk. In multivariable analysis, the use of CD28 CAR T cells was the strongest predictor of ICANS (p = 0.007). Slightly elevated serum NfL levels at leukapheresis predicted ICANS (p = 0.046) supporting its role in predicting risk of neurotoxicity rather than pre-existing neurological disease. CONCLUSIONS: Our results suggest that pre-existing cognitive impairment or neurological history do not increase the risk of ICANS.

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