The outcomes of treatment for people with newly diagnosed FMS-like tyrosine kinase 3 (FLT3)-mutated (FLT3mut+) acute myeloid leukemia (AML) who were not candidates for intense chemotherapy were unsatisfactory. 

For an open-label, phase 3 study, untreated people with FLT3mut+ AML who were ineligible for intense induction chemotherapy were randomly assigned (2:1) to receive gilteritinib (120 mg/d orally) and azacitidine (GIL + AZA) or azacitidine (AZA) alone. Overall survival (OS) was the main outcome measure. A total of 123 patients were randomly assigned to therapy at the interim analysis (August 26, 2020): 74 were assigned to GIL + AZA and 49 were assigned to AZA. 20.3% (GIL + AZA) and 44.9% (AZA) of patients underwent further AML treatment, which included FLT3 inhibitors. The median OS was 9.82 months for GIL + AZA and 8.87 months for AZA (hazard ratio, 0.916; 95% CI, 0.529-1.585; P =.753). Based on the protocol-specified border for futility, the trial was deemed to be closed. 

In both groups, the median event-free survival was 0.03 months. With composite complete remission (CRc) as the standard, the event-free survival was 4.53 months for GIL + AZA and 0.03 months for AZA (hazard ratio, 0.686; 95% CI, 0.433-1.087; P =.156). CRc rates were 58.1% (GIL + AZA) and 26.5% (AZA) (difference, 31.4%; 95% CI, 13.1-49.7; P < .001), respectively. AZA (95.7%) and GIL + AZA (100%) both had similar adverse event (AE) rates; grade ≥3 AEs were 95.9% and 89.4%, respectively. Pyrexia (47.9%) and diarrhea (38.4%) were frequent adverse events (AEs) with GIL + AZA. GIL + AZA and gilteritinib did not have different steady-state trough concentrations of gilteritinib. Compared to AZA, GIL + AZA produced considerably greater CRc rates, but a similar OS. 

Results showed that upfront treatment with GIL + AZA in older/unfit patients with FLT3mut+ AML was safe, tolerable, and clinically active.