Background: Patients with relapsed or refractory acute myeloid leukemia (AML) with mutations within the FMS-like tyrosine kinase 3 gene (FLT3) infrequently possess a reaction to salvage chemotherapy. Gilteritinib is definitely an dental, potent, selective FLT3 inhibitor with single-agent activity in relapsed or refractory FLT3-mutated AML.
Methods: Inside a phase 3 trial, we at random assigned adults with relapsed or refractory FLT3-mutated AML inside a 2:1 ratio to get either gilteritinib (in a dose of 120 mg each day) or salvage chemotherapy. The 2 primary finish points were overall survival and also the number of patients who’d complete remission with full or partial hematologic recovery. Secondary finish points incorporated event-free survival (freedom from treatment failure [i.e., relapse or insufficient remission] or dying) and also the number of patients who’d complete remission.
Results: Of 371 qualified patients, 247 were at random allotted to the gilteritinib group and 124 towards the salvage chemotherapy group. The median overall survival within the gilteritinib group was considerably more than that within the chemotherapy group (9.3 several weeks versus. 5.6 several weeks hazard ratio for dying, .64 95% confidence interval [CI], .49 to .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.).