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The prognosis of relapsed primary central nervous system lymphoma (PCNSL) remains dismal. CAR T-cells are a major contributor to systemic lymphomas, but their use in PCNSL is limited. From the LOC network database, we retrospectively selected PCNSL who had leukapheresis for CAR-T cells from the third line of treatment, and, as controls, PCNSL treated with any treatment, at least in the third line and considered not eligible for ASCT. Twenty-seven patients (median age: 68, median of three previous lines, including ASCT in 14/27) had leukapheresis, of whom 25 received CAR T-cells (tisa-cel: N = 16, axi-cel: N = 9) between 2020 and 2023. All but one received a bridging therapy. The median follow-up after leukapheresis was 20.8 months. The best response after CAR-T cells was complete response in 16 patients (64%). One-year progression-free survival from leukapheresis was 43% with a plateau afterward. One-year relapse-free survival was 79% for patients in complete or partial response at CAR T-cell infusion. The median overall survival was 21.2 months. Twenty-three patients experienced a cytokine release syndrome and 17/25 patients (68%) a neurotoxicity (five grade ≥3). The efficacy endpoints were significantly better in the CAR T-cell group than in the control group (N = 247) (median PFS: 3 months; median OS: 4.7 months; p < 0.001). This series represents the largest cohort of PCNSL treated with CAR T-cells reported worldwide. CAR T-cells are effective in relapsed PCNSL, with a high rate of long-term remission and a reassuring tolerance profile. The results seem clearly superior to those usually observed in this setting., (© 2024 The Authors. American Journal of Hematology published by Wiley Periodicals LLC.)

Abstract: Histologic transformation of Waldenström macroglobulinemia (HT-WM) carries a poor prognosis with standard treatments. Here, we report the first series of HT-WM treated with chimeric antigen receptor T cells showing a high efficacy and no unexpected toxicity., (© 2024 American Society of Hematology. Published by Elsevier Inc. All rights are reserved, including those for text and data mining, AI training, and similar technologies.)

Immunotherapy with chimeric antigen receptor engineered-T cells (CAR-T) has revolutionized the landscape of treatment of relapsed or refractory B-cell. However, the use of autologous T cells has limitations: variable quality of collected effector T cells, duration of the process sometimes incompatible with uncontrolled hemopathy, limited number of available CAR cells, sometimes fatal toxicities, extremely high cost. Natural Killer (NK) cells are an interesting alternative to T cells. NK cells are very powerful cytotoxic effectors that have demonstrated an anti-tumor effect after haploidentical hematopoietic stem cells transplantation or in adoptive cell therapy against a number of solid or hematological tumors. Mainly, they can be used in allogeneic situations without causing major toxic side effects. The sources of NK cells are multiple: cell line, cord blood, peripheral blood, induced pluripotent stem cells. Recent advances in manufacturing engineered CAR-NK cells make it possible to promote antibody-dependent cell-mediated cytotoxicity (ADCC), as well as the activation and persistence of these cells, notably via the cytokine Il-15. The majority of the reports on CAR-NK cells concern pre-clinical or early clinical trials. However, the many advantages of "off-the-shelf" allogeneic CAR-NK cells provide great potential in cancer treatments., (Copyright © 2021. Published by Elsevier Masson SAS.)