Xospata First Monotherapy Approved for Relapsed or Refractory Acute Myeloid Leukemia with FLT3 Mutation

December 2018, Vol 9, No 4 - FDA Approvals, News & Updates


On November 28, 2018, the FDA approved gilteritinib (Xospata; Astellas Pharma) for adult patients with relapsed or refractory acute myeloid leukemia (AML) and an FLT3 mutation, as identified by an FDA-­approved test. The FDA approved gilteritinib using its fast track and priority review and granted it an orphan drug designation.

On the same day, the FDA also approved an expanded indication for the companion diagnostic LeukoStrat CDx FLT3 Mutation Assay, to expand its use for gilteritinib. This companion diagnostic is used to detect FLT3 mutations in patients with AML.

The approval of gilteritinib was based on an interim analysis of the ADMIRAL clinical trial of 138 adults with relapsed or refractory AML and an FLT3 ITD, D835, or I836 mutation, as detected by the LeukoStrat CDx FLT3 Mutation Assay. Oral gilteritinib was used daily until unacceptable toxicity or lack of clinical benefit. At a median follow-up of 4.6 months, 29 (21%) patients achieved a complete remission (CR) or CR with partial hematologic recovery (95% confidence interval, 14.5-28.8). Of the 106 patients who were dependent on red blood cell (RBC) and/or platelet transfusions at baseline, 33 (31.1%) became independent of RBC and platelet transfusions during any 56-day postbaseline period. For the 32 patients who were independent of RBC and platelet transfusions at baseline, 17 (53.1%) remained transfusion-independent during any 56-day postbaseline period.

The most common (≥20%) adverse events were myalgia/arthralgia, transaminase increase, fatigue/malaise, fever, noninfectious diarrhea, dyspnea, edema, rash, pneumonia, nausea, stomatitis, cough, headache, hypotension, dizziness, and vomiting.