Point of care CD19 chimeric antigen receptor (CAR) T-cells for relapsed/refractory acute myeloid leukemia (AML) with aberrant CD19 antigen expression.

Autor: Danylesko I; Division of Hematology and Bone Marrow Transplantation, Sheba Medical Center, Ramat Gan, Israel; Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel. Electronic address: alexivetta@gmail.com., Shem-Tov N; Division of Hematology and Bone Marrow Transplantation, Sheba Medical Center, Ramat Gan, Israel; Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel., Yerushalmi R; Division of Hematology and Bone Marrow Transplantation, Sheba Medical Center, Ramat Gan, Israel; Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel., Jacoby E; Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel; Division of Pediatric Hematology and Oncology, The Edmond and Lily Safra Children's Hospital, Sheba Medical Center, Ramat Gan, Israel., Toren A; Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel; Division of Pediatric Hematology and Oncology, The Edmond and Lily Safra Children's Hospital, Sheba Medical Center, Ramat Gan, Israel., Shouval R; Division of Hematology and Bone Marrow Transplantation, Sheba Medical Center, Ramat Gan, Israel; Department of Medicine, Weill Cornell Medical College, New York, New York, USA; Adult Bone Marrow Transplantation Service, Memorial Sloan Kettering Cancer Center, New York, New York, USA., Itzhaki O; Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel; Ella Lemelbaum Institute of Immuno-Oncology, Sheba Medical Center, Ramat Gan, Israel., Avigdor A; Division of Hematology and Bone Marrow Transplantation, Sheba Medical Center, Ramat Gan, Israel; Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel., Shimoni A; Division of Hematology and Bone Marrow Transplantation, Sheba Medical Center, Ramat Gan, Israel; Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel., Nagler A; Division of Hematology and Bone Marrow Transplantation, Sheba Medical Center, Ramat Gan, Israel; Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
Jazyk: angličtina
Zdroj: Current research in translational medicine [Curr Res Transl Med] 2024 Dec; Vol. 72 (4), pp. 103471. Date of Electronic Publication: 2024 Sep 15.
DOI: 10.1016/j.retram.2024.103471
Abstrakt: Relapsed/refractory (r/r) acute myeloid leukemia (AML) is associated with poor prognosis. CD19 is a B-cell marker, is aberrantly expressed in AML, mostly with t(8; 21)(q22; q22.1). Here we report the results of a phase 2 study giving point of care produced CD19 CAR T- cells for r/r AML with aberrant expression of CD19 (NCT04257175). Lymphodepletion included fludarabine and cyclophosphamide The response was evaluated by bone marrow (BM) aspiration on day 28. Six patients (5 adults and 1 child) were included. Median number of previous chemotherapy lines was 4 (range, 3-8) and four patients received CAR T-cells 8-18 months post allogeneic hematopoietic stem cell transplantation (allo-HSCT). Cytokine release syndrome (CRS) of any grade occurred in all patients, and 1 patient had grade 3 CRS. Immune effector cell-associated neurotoxicity syndrome (ICANS) occurred in 2 patients at low grades. Tocilizumab was administered to 2 patients and corticosteroids to 3 patients. Four patients achieved a complete remission (CR), while 2/6 progressed (PD). Three patients (2 with CR and 1 with PD) underwent allo-HSCT (it was the second transplant in 2) 2-5 months post CAR T-cells infusion. The median duration of response in patients achieving CR was 8.5 (range; 3-14) months. However, all patients eventually died within 5 (1-18) months. In conclusion, CD19 CAR T- cell treatment for AML is feasible and safe. However, the response is short and should be followed by allo-HSCT. Hopefully, future long term results will be improved by combining the CAR T- cell therapy with the emerging novel effective anti-leukemic compounds.
Competing Interests: Declaration of competing interest The authors declare that they have no relevant conflict of interest and no competing financial interests.
(Copyright © 2024. Published by Elsevier Masson SAS.)
Databáze: MEDLINE
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