P14.05.B CAR T-CELL THERAPY DOES NOT LEAD TO MEDIUM-TERM NEUROCOGNITIVE DETERIORATION IN PATIENTS WITH CENTRAL NERVOUS SYSTEM LYMPHOMAS. A LOC NETWORK STUDY

Abstract BACKGROUND Several recent studies have shown promising efficacy of anti-CD19 chimeric antigen receptor (CAR) T-cell therapy in central nervous system (CNS) lymphomas. Data regarding neurotoxicity were reassuring, with rates of severe acute neurotoxicity similar to those described in systemic lymphomas. However, recently published data from our group outlined the risk of prolonged neurologic deterioration in patients who experienced severe neurotoxicity, which is unusual in systemic lymphomas. The aim of this study was to evaluate mid-term neurocognitive outcomes in CNS lymphomas treated with CAR T-cells. MATERIAL AND METHODS Patients were retrospectively selected from the French LOC network database according to the following criteria: 1) CNS lymphoma treated with CAR T-cells at Pitié-Salpêtrière hospital; 2) Isolated CNS relapse at the time of leukapheresis; 3) Availability of neuropsychological follow-up. Neuropsychological assessment was performed as part of the usual care, before CAR T-cell infusion and, in the absence of tumoral progression, 6 weeks (W6), 6 months (M6) and 12 months (M12) after CAR T-cell therapy. RESULTS Of 38 CNS lymphomas who received CAR T-cells between May 2021 and March 2024, 30 patients (median age: 61 years (range: 30-82), 17 women, 14 primary, 16 secondary CNS lymphomas) benefited from repeated neuropsychological assessments. At the time of CAR T-cell infusion, 7 had stable or progressive disease, median Karnofsky Performance Status (KPS) was 75 and median Montreal Cognitive Assessment (MoCA) score was 23.5 (range: 11-29). Eleven patients received tisagenlecleucel, 17 axicabtagene ciloleucel and 2 brexucabtagene autoleucel. Nineteen patients experienced acute neurotoxicity, including 6 cases of grade 3-4 neurotoxicity. Twenty-two patients were assessed up to M12 (all other patients progressed). Clustering of these longitudinal data using a k-means approach revealed at W6 a subgroup of patients (n=22) with stable or improved cognitive functioning and a subgroup (n=8) with worsened cognitive functioning. Membership to these clusters was strongly associated with the occurrence and severity of an acute neurotoxicity (p=0.01). At M12, there was a statistically significant improvement of MoCA score (median 26 vs 23.5, p<0.001) compared to baseline. Scores addressing memory, executive functions, visuo-spatial functions and anxiety/depression also improved, although not significantly. Such improvements were already seen at M6, and applied both to the whole population and to the subgroup who experienced grade 3-4 neurotoxicity. CONCLUSION Mid-term neurocognition follow-up of patients with CNS lymphoma treated by CAR T-cells seems reassuring, with no significant cognitive worsening, even in patients who experienced severe acute neurotoxicity. These results should be confirmed with longer follow-up.