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

There are few effective therapies for relapsed acute myeloid leukemia (AML) after allogeneic hematopoietic stem cell transplantation (allo-HSCT), which has a poor prognosis. Although CD19-targeted chimeric antigen receptor T cell (CAR-T-19) therapy has achieved remarkable success for B-cell malignancies, few successful CAR-T cell therapies in AML have been reported. In this prospective study, we explored the therapeutic effect and clinical safety of the application of CAR-T-38 in 6 AML patients with relapsed post allo-HSCT and CD38 expression. The decitabine (DAC) + HAAG regimen was used to reduce tumor burden, followed by the fludarabine and cyclophosphamide (FC) regimen for lymphodepletion chemotherapy before CAR-T cell infusion. In total, 8.05 (6.1-10) x 10⁶/kg CAR-T-38 were infused by dose escalation over a 3- to 4-day period. At 1, 2 and 4 weeks after CAR-T infusion, 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 of six (83.3%) patients experienced mild (grade I-II) cytokine release syndrome (CRS), and only one patient presented grade III hepatotoxicity. No neurological toxicities were observed, but all six patients had grade III/IV hematological toxicities. The 6-month overall survival (OS) and leukemia-free survival (LFS) rates were 50% and 50%, respectively, and the median OS and LFS were 12.3 and 10.3 months, respectively. The cumulative relapse rates at 3 and 6 months were 25% and 50%, respectively. Multiparameter flow cytometry (FCM) showed that the percentage of CD38-positive blasts remarkably decreased at day 7 and remained at low levels on day 28 after CAR-T cell infusion, but CD38-positive monocytes and lymphocytes were not depleted. 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. (NCT04351022)