CD38-Directed CAR-T Cell Therapy: A Novel Immunotherapy Strategy for Relapsed Acute Myeloid Leukemia after Allogeneic Hematopoietic Stem Cell Transplantation

Background: There are few effective therapies for relapsed acute myeloid leukemia (AML) after allogeneic hematopoietic stem cell transplantation (allo-HSCT), which has a poor prognosis. Few successful CAR-T cell therapies in AML have been reported. Methods: In this prospective study, we explored the therapeutic effect and clinical safety of the application of CAR-T-38 in six AML patients with relapsed post allo-HSCT and CD38 expression. Findings: After one, two and four weeks after CAR-T infusion 8·05 (6·1-10) x 106/kg CAR-T-38, two (33·3%), four (66·7%) and four (66·7%) of six patients achieved complete remission (CR) or CR with incomplete count recovery (CRi), respectively. Five patients experienced mild (grade I-II) cytokine release syndrome (CRS), and only one patient presented grade III hepatotoxicity. The median OS and LFS were 12·3 and 10·3 months, respectively. The cumulative relapse rates at three and six months were both 50%. One patient relapsed after the first CAR-T-38 and got re-remission undergoing the second CAR-T-38. Multiparameter flow cytometry (FCM) showed that CD38-positive blasts remarkably decreased after CAR-T cell infusion, but CD38-positive monocytes and lymphocytes were not depleted. Interpretation: This study is the first to indicate that CAR-T-38 therapy is a promising effective and safe approach for patients with relapsed AML after allo-HSCT. Trial Registration: (NCT04351022) Funding: This work was supported by research grants from the National Natural Science Foundation of China (81873443). Declaration of Interests: The authors declare no potential conflicts of interest. Ethics Approval Statement: This study was approved by the Ethics Committee of the First Affiliated Hospital of Soochow University and was conducted in accordance with the principles of the Declaration of Helsinki. All patients provided written informed consent.