Gilteritinib + Ven/Aza in ND FLT3-mutated AML: Phase II long-term results

During the 67th American Society of Hematology (ASH) Annual Meeting and Exposition, December 6–9, 2025, Orlando, US, Roberta Azevedo reported long-term results from a single-center phase II trial (NCT04140487) of gilteritinib in combination with venetoclax (Ven) and azacitidine (Aza) in 30 patients with newly diagnosed (ND) FLT3-mutated acute myeloid leukemia (AML) unfit for intensive chemotherapy. The primary endpoint was the complete remission (CR) and CR with incomplete recovery (CRi) rate. Secondary endpoints included measurable residual disease (MRD) negativity rate, duration of response (DoR), overall survival (OS), and adverse events (AEs).

Key data: All patients (100%) achieved a CR/CRi or morphologic leukemia-free state (MLFS), including 90% achieving CR, 6% CRi, and 4% MLFS. At a median follow-up of 41.5 months, median OS was 29.7 months, and 3-year OS was 46%. MRD negativity was achieved in 93% of patients. Among 11 patients who relapsed, the median DoR was 19.9 months. Infectious complications were the most common AE, occurring in 60% of patients.

Key learning: Triple therapy with gilteritinib + Ven/Aza demonstrated durable responses in patients with ND FLT3-mutated AML, with outcomes that appear superior compared with historical data for Ven/Aza, warranting further investigation in randomized trials.