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Tibsovo Now Indicated for First-Line Treatment of AML with IDH1 Mutation

On May 2, 2019, the FDA expanded the indication for ivosidenib (Tibsovo; Agios Pharmaceuticals), an oral isocitrate dehydrogenase-1 (IDH1) inhibitor, to include the treatment of patients with newly diagnosed acute myeloid leukemia (AML) and a susceptible IDH1 mutation, as detected by an FDA-approved companion diagnostic test, who are aged ≥75 years or who have comorbidities that preclude the use of intensive induction chemotherapy. Tibsovo was previously approved for the treatment of patients with relapsed or refractory AML with a susceptible IDH1 mutation.

The FDA approved this new indication for ivosidenib based on results of the phase 1, single-arm, multicenter, AG120-C-001 clinical trial that included 28 patients with newly diagnosed AML and an IDH1 mutation detected by the RealTime IDH1 Assay (Abbott Laboratories). The median patient age was 77 years (range, 64-87 years), and 22 (79%) patients had secondary AML.

Patients received ivo­sidenib at a starting dose of 500 mg daily until disease progression, unacceptable toxicity, or stem-cell transplant. Median treatment duration was 4.3 months (range, 0.3-40.9 months).

Treatment efficacy was measured by rate of complete remission (CR) or complete remission with partial hematologic improvement (CRh), the duration of CR+CRh, and the rate of conversion from transfusion dependence to transfusion independence. Results showed that 8 (28.6%) of the 28 patients achieved CR; 4 (14.3%) achieved CRh, and 12 (42.9%) achieved CR+CRh. In addition, 7 (41.2%) of the 17 patients who were dependent on transfusions at baseline achieved transfusion independence during any 56-day period after baseline.

“The phase 1 results for Tibsovo demonstrated that this oral, single agent therapy can induce durable responses in newly diagnosed AML patients with an IDH1 mutation,” said Gail J. Roboz, MD, Professor of Medicine and Director, Clinical and Translational Leukemia Program, Weill Medical College of Cornell University and NewYork-Presbyterian Hospital, New York City.

The most common (≥25%) adverse events associated with ivosidenib treatment in the trial included diarrhea, fatigue, edema, decreased appetite, leukocytosis, nausea, arthralgia, abdominal pain, dyspnea, differentiation syndrome, and myalgia.

The prescribing information for ivosidenib includes a boxed warning regarding the risk for differentiation syndrome, which may be life-threatening or fatal, if not treated.

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