FDA Approves Targeted Drug to Treat Relapsed or Refractory AML With FLT3 Mutation

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Once-daily gilteritinib pills have been approved to treat adult patients with relapsed or refractory acute myeloid leukemia (AML) with a FLT3 mutation. Approximately 25% to 30% of patients with AML have this mutation, which is associated with an aggressive form of the disease and carries a higher risk of relapse.

A new drug has received approval to treat adult patients with relapsed or refractory acute myeloid leukemia (AML) with a FLT3 mutation. Xospata (gilteritinib) is approved to treat adults whose mutation is detected by an FDA-approved test. The FDA also approved an expanded indication for the LeukoStrat CDx FLT3 Mutation Assay as a companion diagnostic to be used with the therapy.

Gilteritinib is a once-daily pill that was approved based on an interim analysis of a clinical trial with 138 patients with relapsed or refractory AML and a confirmed FLT3 mutation. The therapy targets 2 different FLT3 mutations: FLT3 internal tandem duplication and FLT3 tyrosine kinase domain.

“Approximately 25% to 30% of patients with AML have a mutation in the FLT3 gene,” Richard Pazdur, MD, director of the FDA’s Oncology Center of Excellence and acting director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research, explained in a statement. “These mutations are associated with a particularly aggressive form of the disease and a higher risk of relapse.”


The FLT3 mutation is the most common gene mutation in AML. When the gene is mutated, it allows leukemic cancer cells to grow in an uncontrolled manner unless it is turned off by a drug.

According to Alexander Perl, MD, MS, an associate professor of Hematology-Oncology in the Perelman School of Medicine at the University of Pennsylvania and the Abramson Cancer Center, who led the clinical trials, the approval “brings a new, highly-effective, and well-tolerated treatment option to the clinic for a group of truly high-risk patients who, until today, had no specific therapies available beyond chemotherapy to treat their disease.”

The phase 3 ADMIRAL trial randomized patients to receive gilteritinib or standard chemotherapy. Of the patients who received gilteritinib, 21% achieved complete remission (CR) or CR with partial hematologic recovery (CRh). Median duration of CR/CRh was 4.6 months.

A safety evaluation of 292 patients with relapsed or refractory AML who were treated with 120 mg gilteritinib daily found that the most common adverse reactions were myalgia/arthralgia (42%), transaminase increase (41%), fatigue (40%), fever (35%), noninfectious diarrhea (34%), dyspnea (34%), edema (34%), rash (30%), pneumonia (30%), nausea (27%), stomatitis (26%), cough (25%), headache (21%), hypotension (21%), dizziness (20%), and vomiting (20%).

The ADMIRAL trial is still ongoing.

“Often, salvage therapy is used to stabilize aggressive leukemia before a patient receives a bone marrow transplant that we hope can be curative,” Perl said in a statement. “Having a low-toxicity but highly-active drug like gilteritinib means that relapsed or refractory patients not only are more likely to undergo transplant, but also they remain stronger at the time of transplant and are better able to withstand the surgery and recovery.”