Control effect of Dasatinib on the treatment of acute myeloid leukemia and adverse events of CD123 targeting CAR-T: a case report and literature review

Abstract

Objective To preliminarily explore the efficacy of chimeric antigen receptor T cells (CAR-T) targeting CD123 in the treatment of acute myeloid leukemia (AML) and the role of dasatinib in the treatment of CD123 targeting CAR-T induced side effects. Methods Clinical data of 1 patient with relapsed AML admitted to No.920 Hospital of PLA Joint Logistic Support Force in September, 2019 were collected.The patient relapsed after previous multi-line chemotherapy and was treated with CD123 targeting CAR-T therapy.The routine blood changes of the patient after treatment were observed.Dasatinib was used when agranulocytosis occurred, 40 mg orally 3 times per day, and was stopped when agranulocytosis was relieved.Changes in blood cells, CAR-T amplification, and disease control were observed.The patient was followed up for over 1 year. Results Flow cytometry for bone marrow showed that minimal residual disease negative result was observed in 30 d after infusion.The patient remained disease-free for over 1 year.After CD123 CAR-T cells infusion, significant expansion of CAR-T cells was observed, accompanied by granulocyte deficiency and cytokine release syndrome (CRS).After using dasatinib, inhibition of CAR-T cell expansion was observed, accompanied by blood cell recovery, and CRS symptoms were alleviated.After stop of dasatinib, CAR-T cells expanded again and blood cells decreased again. Conclusion CAR-T cells targeting CD123 have certain efficacy in the treatment for relapsed AML.Dashatinib has a blocking effect on the amplification and function of CAR-T, which can alleviate bone marrow suppression caused by CD123 targeting CAR-T and avoid severe CRS.

Keywords

• chimeric antigen receptor t cells
• acute myeloid leukemia
• cd123 antigen
• dashatinib
• cytokine release syndrome