P12.03.B CAN COGNITIVE PERFORMANCE PREDICT NEUROTOXICITY INCIDENCE FOLLOWING CHIMERIC ANTIGEN RECEPTOR T-CELL THERAPY FOR LYMPHOMA?

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Abstract BACKGROUND Chimeric antigen receptor T-cell (CAR-T) therapy has revolutionised the landscape of cancer treatment, particularly in haematological malignancies, and while these therapies have demonstrated significant efficacy against malignancies, they are associated with a spectrum of side effects. Cytokine Release Syndrome (CRS) and Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS) are unique to CAR-T cell therapy and distinguish it from other forms of autoimmune toxicity. Predicting which patients will develop neurotoxicity remains a challenge. The pattern of ICANS is cognitive dysfunction, suggesting a plausible relationship between cognitive status and neurotoxicity. Understanding the interplay between cognitive function and neurotoxicity may provide valuable insights for early detection. The primary endpoint of this study was to investigate whether the cognitive performance of patients at the time of leukapheresis is associated with the subsequent development of ICANS. MATERIAL AND METHODS We report here on a prospective study of an adult patient population with aggressive B-cell lymphoma treated with CAR-T cell therapy at our centre between May 2020 and November 2023. All patients underwent neurological examination, cerebral MRI and global cognitive assessment using the Montreal Cognitive Assessment (MoCA) test with a cut-off of less than 26 points. We retrospectively recorded total metabolic tumour volume (TMTV) and International Prognostic Index (IPI) at lymphodepletion. Biological data including lactate dehydrogenase (LDH), albumin, ferritin and C-reactive protein (CRP) were also collected at the time of treatment. A retrospective analysis of pre-infusion serum neurofilament light chain (NfL) levels at the time of the decision to proceed with CAR-T cell therapy and at the time of treatment was performed. RESULTS 156 patients, median age 64 years (range 21 to 79 years), 55 females / 101 males, all treated for lymphoma, were included in this study. The mean MoCA score was 26 (range 12 to 30 points), 63 patients (40%) had a MoCA test below the cut-off at baseline. Following infusion of CAR T cells, 32% of patients developed ICANS within 6 days (grade 1-2: 72%; grade 3-4: 30%). The most common sign of neurotoxicity was cognitive impairment. In univariate analyses, the occurrence of ICANS was not significantly associated with baseline cognitive performance (p 0.58). As the study is ongoing, an update on the results will be available at the EANO meeting. CONCLUSION Neurotoxicity associated with CAR-T therapies occurs in one third of patients. This study does not suggest an association between the occurrence of ICANS and baseline cognitive performance. Despite progress in understanding the mechanisms underlying neurotoxicity, predicting its occurrence remains a challenge.

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