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.
Bouille et al. (Wed,) studied this question.