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)
No relevant conflicts of interest to declare.
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