CD7-directed CAR T-cell therapy: a potential immunotherapy strategy for relapsed/refractory acute myeloid leukemia

Abstract

Relapsed/refractory acute myeloid leukemia (AML) patients generally have a dismal prognosis and the treatment remains challenging. Due to the expression of CD7 on 30% AML and not on normal myeloid and erythroid cells, CD7 is an attractive target for immunotherapy of AML. CD7-targeted CAR T-cells had demonstrated encouraging efficacy in xenograft models of AML. We report here on the use of autologous CD7 CAR T-cells in the treatment of a relapsed/refractory AML patient with complex karyotype, TP53 deletion, FLT3-ITD mutation, and SKAP2-RUNX1 fusion gene. Before the CAR T-cell therapy, the patient achieved partial remission with IA regimen and attained complete remission after reinduction therapy (decitabine and venentoclax). Relapse occurred after consolidation (CLAG regimen). Then she failed CLIA regimen combined with venetoclax and exhibited resistance to FLT3 inhibitors. Bone marrow showed 20% blasts (CD7+ 95.6%). A total dose of 5 × 106/kg CD7 CAR T-cells was administered after the decitabine +FC regimen. Seventeen days after CAR T-cells infusion, she achieved morphologic leukemia-free state. The patient developed grade 3 cytokine release syndrome. No severe organ toxicity or immune effector cell-associated neurotoxicity syndrome was observed. In summary, the autologous CD7 CAR T-cell therapy could be considered a potential approach for AML with CD7 expression (NCT04762485).Trial registration Clinical Trials.gov, NCT04762485. Registered on February 21, 2021, prospectively registered.

Keywords: Acute myeloid leukemia; CD7; Chimeric antigen receptor T‑cells; Relapsed/refractory.

Conflict of interest statement

The authors declare that they have no competing interests.

© 2022. The Author(s).

Figures

Fig. 1

CD7 CAR T-cell therapy regime and clinical characteristic after infusion. a Schematic of the CD7 CAR T-cell therapy regimen, the total infusion dose of CAR T-cells was 5 × 106/kg for 2 days; b qPCR analysis of the CAR T-cells copies in PB after the infusion. The highest level was on day 14. The patient still has 5,084 CAR-T copies/µg  by day 28; c Change of the temperature and CRP after CD7 CAR T-cells infusion; d Change of cytokines after CD7 CAR T-cells infusion; e Change of the blood cell counts after CD7 CAR T-cells infusion

Fig. 2

Treatment response of CD7 CAR T-cells infusion. a BM morphology before and after CD7 CAR T-cells infusion; b Change of percentage of blasts and MRD in BM after CD7 CAR T-cells infusion; c Flow cytometry analysis in BM before and after CD7 CAR T-cells infusion; d Change of molecular markers before and after CD7 CAR T-cells infusion