P14.07.B CAR T-CELL THERAPY IN PRIMARY CENTRAL NERVOUS SYSTEM LYMPHOMAS: A MULTICENTER RETROSPECTIVE STUDY FROM THE LOC NETWORK

Abstract BACKGROUND The use of CAR T-cell therapy has been delayed in primary central nervous system lymphomas (PCNSL) due to the fear of unacceptable neurotoxicity. However, several recent small series (<30 patients) have shown promising results in heavily pretreated patients. The aim of this work was to confirm the interest of CAR T-cells in a larger cohort of PCNSL, with a longer follow-up. MATERIAL AND METHODS We retrospectively selected from the French LOC network database the patients with PCNSL treated with CAR T-cells and analyzed their characteristics and outcomes. RESULTS Sixty-seven patients with PCNSL (43 men, 24 women) from 24 centers received CAR T-cells between January 2020 and October 2024. Their median age was 66 years (range: 31-82). Their median ECOG score was 1. At the time of leukapheresis, brain involvement was present in 84% of patients, cerebrospinal fluid (CSF) involvement in 25%, and ocular involvement in 12%. Patients had received a median of 2 prior lines of therapy (range: 1-6), including autologous stem cell transplantation in 30/67 cases. Sixty-five patients received bridging therapy before CAR T-cells. Thirty-eight patients (57%) received axicabtagene clioleucel, 20 (30%) tisagenlecleucel and 7 (10%) lisocabtagene maraleucel. Patients were followed for a median duration of 12 months (maximum: 47 months). During the follow-up, the best response was a complete response in 39 patients (58%) and a partial response in 14 patients (21%). Only 4 patients relapsed more than 12 months after the CAR T-cell infusion. Relapse-free survival was significantly better in patients in complete or partial response at CAR T-cell infusion (2-year RFS 55,6% vs 27,6%. P= 0,01). The 1-year and two-year progression-free survival rates were 50 % and 44%, respectively. The 1-year and two-year overall survival rates were 66% et 50%, respectively. Cytokine release syndrome (CRS) occurred in 95% of patients, with grade III-IV CRS in 4%. Immune effector cell-associated neurotoxicity syndrome (ICANS) was observed in 69% of patients, with 27% experiencing grade ≥ III events. CONCLUSION This work confirms the interest of CAR T-cells in PCNSL, in a larger cohort with a follow-up up to 4 years, with a high percentage of long-term remission and a reassuring tolerance profile in a population of heavily pre-treated patients. Future studies are warranted to clarify the exact positioning of this treatment within the therapeutic arsenal for the disease.