Efficacy of CAR-T Cells in Primary Central Nervous System Lymphomas: the French Experience of the National LOC Network

Introduction: Primary central nervous system lymphoma (PCNSL) is mainly a diffuse large B cell lymphoma (DLBCL) with a non-germinal center B cell (non-GCB) origin. Relapsed/refractory (R/R) PCNSLs are associated with a poor prognosis and an unmet medical need. Chimeric antigen receptor (CAR)-T cells targeting CD19 demonstrated remarkable efficacy, leading to their commercial approval for R/R DLBCL, but no data are currently available for PCNSL. Methods: The French network for oculo-cerebral lymphomas (LOC) database prospectively records all PCNSL cases from 32 French centers. We retrospectively analyzed this national database in order to collect all cases of R/R PCNSLs treated with commercially available CAR-T cells. The main objective was to evaluate the safety and efficacy of CAR-T therapy in this setting. Results: Between January 2020 and March 2021, we identified 9 patients with R/R PCNSL who received commercial anti-CD19 CAR-T cells (7 tisagenlecleucel and 2 axicabtagene ciloleucel). At time of infusion, the median age was 67 years old (range, 48 – 75). Eight patients had a brain parenchymal involvement, including one with eye localization, and 1 had an isolated cerebrospinal fluid infiltration. The median number of prior therapies before leukapheresis was 3 (2 – 5) and 4 patients had progressive disease at time of CAR-T infusion. All patients received a lymphodepleting chemotherapy consisting of cyclophosphamide and fludarabine before CAR-T infusion. The median follow-up was 2.4 months. Six patients experienced cytokine release syndrome (CRS, any grade), including 1 patient with CRS of grade 3 or higher. Immune cell-associated neurotoxicity syndrome (ICANS) of any grade occurred in 5 patients, including 2 patients with ICANS of grade 3 or higher. Four patients received tocilizumab and corticosteroids. The overall response rate (ORR) at 1-month was 62%, with 25% achieving a complete response (CR). Best ORR and CR were 87% and 37% respectively. The overall survival is presented in Figure 1. The updated results will be available and presented during the 2021 ICML meeting. Conclusion: To our knowledge, this study represents the largest cohort of patients treated with anti-CD19 CAR-T cells for R/R PCNSL. Despite a short follow-up, our results suggest that commercial CAR-T cells may be an efficient option to treat R/R PCNSL, with no unexpected toxicity. Large clinical trials are needed to confirm these encouraging results. Overall survival for the 9 R/R PCNSL patients treated with anti-CD19 CAR-T cells Keywords: Cellular therapies Conflicts of interests pertinent to the abstract M. Alcantara Consultant or advisory role: Novartis, Janssen S. Choquet Consultant or advisory role: Novartis, Janssen, Roche, Celgène, Takeda, Sandoz, Sanofi