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

Leukemia. 2022 Nov;36(11):2596-2604. doi: 10.1038/s41375-022-01703-0. Epub 2022 Sep 23.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cytokine Release Syndrome
  • Hematopoietic Stem Cell Transplantation*
  • Immunotherapy, Adoptive / adverse effects
  • Immunotherapy, Adoptive / methods
  • Lectins, C-Type
  • Leukemia, Myeloid, Acute* / drug therapy
  • Mice
  • Receptors, Chimeric Antigen*

Substances

  • Receptors, Chimeric Antigen
  • Lectins, C-Type