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

in European journal of neurology by Renata Ursu, Claudia Barsan, Roberta Di Blasi, Catherine Belin, Stefania Cuzzubbo, Mohamed El Soudany, Caterina Cristinelli, Raghunath Sivapragassame, Amani Ouedrani, Catherine Thieblemont, Sophie Caillat-Zucman, Antoine F Carpentier

TLDR

  • Scientists studied the risk factors for a serious complication called ICANS in patients who received CAR T-cell therapy for cancer.
  • They found that using CD28 CART cells and slightly elevated serum NfL levels predicted ICANS, but pre-existing cognitive or neurological problems did not.

Abstract

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. 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. 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. Our results suggest that pre-existing cognitive impairment or neurological history do not increase the risk of ICANS.

Overview

  • The study evaluated the impact of baseline cognitive status and pre-existing neurological injury on the occurrence of Immune effector cell-associated neurotoxicity syndrome (ICANS) in adult patients treated with CAR T-cell therapy for aggressive B-cell lymphoma.
  • The study recruited 156 adult patients between May 2020 and December 2023 and used neurological examination, cerebral MRI, and cognitive assessment measured by the Montreal Cognitive Assessment (MoCA) to evaluate the factors.
  • The primary objective of the study was to identify the factors that predict the occurrence of ICANS, a common and serious complication of CAR T-cell therapy.

Comparative Analysis & Findings

  • The study found that 32.7% of the patients developed ICANS, but there was no significant association between the onset of ICANS and baseline cognitive performance.
  • The use of CD28 CAR T cells was the strongest predictor of ICANS, and slightly elevated serum NfL levels at leukapheresis also predicted ICANS.
  • Pre-existing neurological injury and cognitive impairment at baseline were not associated with increased risk of ICANS.

Implications and Future Directions

  • The study's findings suggest that pre-existing cognitive impairment or neurological history do not increase the risk of ICANS, and that CD28 CAR T cells and serum NfL levels may be useful predictors of ICANS.
  • Future studies could investigate the relationship between ICANS and immune cell subsets, as well as the potential role of CD28 CAR T cells in predicting neurotoxicity.
  • The study's findings may inform the development of strategies to mitigate ICANS in patients receiving CAR T-cell therapy.
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