FDA Approval Summary: Gilteritinib for relapsed or refractory acute myeloid leukemia with a FLT3 mutation.

On November 28, 2018, the Food and Drug Administration approved gilteritinib (Xospata; Astellas, Northbrook, IL), a small molecule FMS-like tyrosine kinase 3 (FLT3) inhibitor, for treatment of relapsed or refractory (R/R) acute myeloid leukemia (AML) with a FLT3 mutation as detected by an FDA-approved test. In the ADMIRAL Study, patients were randomized 2:1 to receive gilteritinib or standard chemotherapy and stratified by response to first-line treatment and intensity of prespecified chemotherapy. Efficacy was established on interim analysis based on complete remission (CR)+CR with partial hematologic recovery (CRh) rate, duration of CR+CRh, and conversion from transfusion dependence (TD) to transfusion independence (TI) in 138 patients in the gilteritinib arm. With median follow-up of 4.6 months (95% CI 2.8-15.8 months) at interim analysis, the CR+CRh rate was 21% (95% confidence interval [CI], 15%-29%), median duration of CR+CRh was 4.6 (range, 0.1-15.8+) months, and conversion from TD to TI was 31%. Revised labeling approved May 29, 2019 included the results of the final analysis, showing an improvement in overall survival (OS) with gilteritinib compared to chemotherapy (hazard ratio [HR] 0.64 [95% CI 0.49-0.83], 1-sided p=0.0004); median OS 9.3 months vs 5.6 months). The OS benefit was observed in both high and low chemotherapy intensity subgroups. Labeling includes a boxed warning for differentiation syndrome (DS) and warnings for posterior reversible encephalopathy syndrome, QT prolongation, pancreatitis, and embryo-fetal toxicity. Safe use requires frequent monitoring of electrocardiograms and blood chemistries. Assessments of long-term safety are pending.