Enasidenib, a New Targeted Therapy Approved for Relapsed or Refractory AML, Shows Complete Remission in Some Patients

Best Practices in Hematologic Malignancies – December 2017 Vol 8

On August 1, 2017, the FDA approved enasidenib (Idhifa), an isocitrate dehydrogenase-2 inhibitor, for the treatment of adults with relapsed or refractory acute myeloid leukemia (AML) who have the IDH2 genetic mutation. The FDA approved enasidenib for use based on results of a companion diagnostic—the RealTime IDH2 Assay (by Abbott Laboratories)—which was approved by the FDA on the same day and is specifically designed to detect mutations in the IDH2 gene in patients with AML. If the RealTime IDH2 Assay detects the IDH2 mutation in the patient’s blood or bone marrow, that patient may be eligible for treatment with enasidenib. The FDA granted enasidenib a priority review and an orphan drug designation.

“Idhifa is a targeted therapy that fills an unmet need for patients with relapsed or refractory AML who have an IDH2 mutation,” said Richard Pazdur, MD, Director of the FDA’s Oncology Center of Excellence. “The use of Idhifa was associated with a complete remission in some patients and a reduction in the need for both red cell and platelet transfusions.” Enasidenib works by blocking several enzymes that promote cell growth.

The FDA approval of enasidenib was based on a single-arm clinical trial that enrolled 199 patients with relapsed or refractory AML and had an IDH2 mutation that was detected by the RealTime IDH2 Assay. The study’s primary end points were complete remission (CR) and CR with partial hematologic recovery (CRh).

Patients received at least 6 months of treatment with enasidenib; of the 199 patients in the study, 19% had CR lasting for a median duration of 8.2 months, and 4% of patients had CRh lasting for a median duration of 9.6 months.

Furthermore, at the start of the study, 157 patients required transfusions of blood or platelets because of AML; of these patients, 34% stopped the transfusions after initiating treatment with enasidenib.

The common side effects reported with enasidenib were nausea, vomiting, diarrhea, increased bilirubin levels, and decreased appetite. Women who are pregnant or are breastfeeding should not take enasidenib, which may cause harm to the fetus or the newborn baby.

The prescribing information of enasidenib includes a boxed warning about the risk for differentiation syndrome with this drug, which can be fatal if not properly treated. When this syndrome is suspected, patients should receive corticosteroids and be monitored closely.

The National Cancer Institute estimates that approximately 21,380 Americans will be diagnosed with AML and 10,590 patients will die of the disease in 2017.

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Last modified: August 10, 2023

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