BACKGROUND: Patients with relapsed or refractory acute myeloid leukemia (AML) 
with mutations in the FMS-like tyrosine kinase 3 gene (FLT3) infrequently have a 
response to salvage chemotherapy. Gilteritinib is an oral, potent, selective 
FLT3 inhibitor with single-agent activity in relapsed or refractory FLT3-mutated 
AML.
METHODS: In a phase 3 trial, we randomly assigned adults with relapsed or 
refractory FLT3-mutated AML in a 2:1 ratio to receive either gilteritinib (at a 
dose of 120 mg per day) or salvage chemotherapy. The two primary end points were 
overall survival and the percentage of patients who had complete remission with 
full or partial hematologic recovery. Secondary end points included event-free 
survival (freedom from treatment failure [i.e., relapse or lack of remission] or 
death) and the percentage of patients who had complete remission.
RESULTS: Of 371 eligible patients, 247 were randomly assigned to the 
gilteritinib group and 124 to the salvage chemotherapy group. The median overall 
survival in the gilteritinib group was significantly longer than that in the 
chemotherapy group (9.3 months vs. 5.6 months; hazard ratio for death, 0.64; 95% 
confidence interval [CI], 0.49 to 0.83; P<0.001). The median event-free survival 
was 2.8 months in the gilteritinib group and 0.7 months in the chemotherapy 
group (hazard ratio for treatment failure or death, 0.79; 95% CI, 0.58 to 1.09). 
The percentage of patients who had complete remission with full or partial 
hematologic recovery was 34.0% in the gilteritinib group and 15.3% in the 
chemotherapy group (risk difference, 18.6 percentage points; 95% CI, 9.8 to 
27.4); the percentages with complete remission were 21.1% and 10.5%, 
respectively (risk difference, 10.6 percentage points; 95% CI, 2.8 to 18.4). In 
an analysis that was adjusted for therapy duration, adverse events of grade 3 or 
higher and serious adverse events occurred less frequently in the gilteritinib 
group than in the chemotherapy group; the most common adverse events of grade 3 
or higher in the gilteritinib group were febrile neutropenia (45.9%), anemia 
(40.7%), and thrombocytopenia (22.8%).
CONCLUSIONS: Gilteritinib resulted in significantly longer survival and higher 
percentages of patients with remission than salvage chemotherapy among patients 
with relapsed or refractory FLT3-mutated AML. (Funded by Astellas Pharma; 
ADMIRAL ClinicalTrials.gov number, NCT02421939.).