On November 28, 2018, the U.S. Food and Drug Administration (FDA) approved gilteritinib (Xospata®) for treatment of adult patients who have relapsed or refractory acute myeloid leukemia (AML) with an FLT3 mutation as detected by an FDA-approved test.
The FDA also approved an expanded indication for a companion diagnostic, to include use with gilteritinib. The LeukoStrat CDx FLT3 Mutation Assay, developed by Invivoscribe Technologies, Inc., is used to detect the FLT3 mutation in patients with AML.
Approval of gilteritinib was based on an interim analysis of the ADMIRAL trial (NCT02421939), which included 138 adult patients with relapsed or refractory AML having a FLT3 ITD, D835, or I836 mutation by the LeukoStrat CDx FLT3 Mutation Assay. Gilteritinib was given orally at a dose of 120 mg daily until unacceptable toxicity or lack of clinical benefit. After a median follow-up of 4.6 months (range = 2.8–15.8), 29 patients achieved complete remission (CR) or CR with partial hematologic recovery (21%, 95% CI = 14.5, 28.8).
Among 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 post-baseline period. For the 32 patients who were independent of both RBC and platelet transfusions at baseline, 17 (53.1%) remained transfusion-independent during any 56-day post-baseline period.
The most common adverse reactions occurring in ≥ 20% of patients were myalgia/arthralgia, transaminase increase, fatigue/malaise, fever, noninfectious diarrhea, dyspnea, edema, rash, pneumonia, nausea, stomatitis, cough, headache, hypotension, dizziness, and vomiting.
The recommended gilteritinib dose is 120 mg orally once daily.
FDA granted this application fast track and priority review, as well as orphan product designation. A description of FDA expedited programs is in the Guidance for Industry: Expedited Programs for Serious Conditions-Drugs and Biologics.
Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System or by calling 800-FDA-1088.
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