An all-oral triplet regimen (decitabine/cedazuridine, venetoclax, and gilteritinib) for newly diagnosed and relapsed/refractory FLT3-mutated AML and high-risk MDS

Combination of FLT3 inhibitors with azacitidine and venetoclax has promising activity in FLT3 -mutated acute myeloid leukemia (AML). In this phase I/II study, we evaluated the safety and efficacy of an all-oral regimen of decitabine/cedazuridine, venetoclax, and gilteritinib in adults with FLT3 -mutated AML and other myeloid malignancies. A total of 46 patients were enrolled (19 with newly diagnosed [ND] AML and 27 with relapsed/refractory [R/R] disease). The median age was 72 years in ND AML and 67 years in R/R cohort; 38 patients (83%) had FLT3 -ITD mutations. The composite complete remission (CRc) rate was 74% in ND-AML and 42% in R/R-AML, with CR rates of 58% and 21%, respectively. Two nonresponders in the ND group had prior treatment for antecedent myeloid malignancies. The 18-month relapse-free survival and overall survival were 67% and 54% in the ND cohort, respectively. During induction, the median time to ANC ( > 0.5 × 10⁹/L) and platelet ( > 50 ×10⁹/L) recovery was 37 and 27 days, respectively, in ND AML. During consolidation, median treatment durations were 3 days for DEC-C, 7 days for venetoclax, and 28 days for gilteritinib. This all-oral triplet regimen shows promising activity in ND FLT3 -mutated AML; myelosuppression remains a key toxicity requiring dose adjustment.