Characteristics of anti-CLL1 based CAR-T therapy for children with relapsed or refractory acute myeloid leukemia: the multi-center efficacy and safety interim analysis

• Published in: Leukemia Vol. 36; no. 11; pp. 2596 - 2604
• Main Authors: Zhang, Hui, Bu, Chaoke, Peng, Zhiyong, Li, Guangchao, Zhou, Zhao, Ding, Wen, Zheng, Yongwei, He, Yingyi, Hu, Zhengbin, Pei, Kunlin, Luo, Min, Li, Chunfu
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.11.2022; Nature Publishing Group
• Subjects: 13/106; 13/109; 13/31; 59/5; 631/67/1059/2325; 631/67/1059/602; 64/60; 692/308/2779/109/1940; 82/1; Acute myeloid leukemia; Animals; Antigens; Autografts; Cancer Research; Children; Clinical trials; Critical Care Medicine; Cytokine Release Syndrome; Cytokines; Effectiveness; Health services; Hematology; Hematopoietic Stem Cell Transplantation; Immunotherapy; Immunotherapy, Adoptive - adverse effects; Immunotherapy, Adoptive - methods; Intensive; Internal Medicine; Lectins, C-Type; Leukemia; Leukemia, Myeloid, Acute - drug therapy; Lymphocytes; Lymphocytes T; Medicine; Medicine & Public Health; Mice; Minimal residual disease; Oncology; Patients; Receptors, Chimeric Antigen; Remission; Remission (Medicine); Safety; Stem cell transplantation; Stem cells
• ISSN: 0887-6924; 1476-5551; 1476-5551
• DOI: 10.1038/s41375-022-01703-0

C-type lectin-like molecule-1 (CLL1) is preferentially expressed on acute myeloid leukemia (AML) stem cells and AML blasts, which can be considered as AML-associated antigen. Anti-CLL1-based CAR-T cells exhibited effective tumor-killing capacity in vitro and in AML-bearing mouse model. In this report, eight children with relapsed or refractory AML (R/R-AML) were recruited for a phase 1/2 clinical trial of autologous anti-CLL1 CAR-T cell immunotherapy. The objectives of this clinical trial were to evaluate the safety and the preliminary efficacy of anti-CLL1 CAR-T cell treatment. Patients received one dose of autologous anti-CLL1 CAR-T cells after lymphodepletion conditioning. After CAR-T treatment, patients developed grade 1–2 cytokine release syndrome (CRS) but without any lethal events. 4 out of 8 patients achieved morphologic leukemia-free state (MLFS) and minimal residual disease (MRD) negativity, 1 patient with MLFS and MRD positivity, 1 patient achieved complete remission with incomplete hematologic recovery (CRi) but MRD positivity, 1 patient with partial remission (PR), and 1 patient remained at stable disease (SD) status but had CLL1-positive AML blast clearance. These results suggested that anti-CLL1-based CAR-T cell immunotherapy can be considered as a well-tolerated and effective option for treating children with R/R-AML.