On July 20, 2018, the U.S. Food and Drug Administration approved ivosidenib (Tibsovo) for adult patients with relapsed or refractory acute myeloid leukemia (AML) with a susceptible IDH1 mutation as detected by an FDA-approved test.
Approval was based on an open-label, single-arm, multicenter clinical trial (AG120-C-001, ClinicalTrials.gov identifier NCT02074839) that included 174 adult patients with relapsed or refractory AML with an IDH1 mutation confirmed using the IDH1 Assay, the FDA-approved test for selection of patients with AML for treatment with ivosidenib. Ivosidenib was given orally at a starting dose of 500 mg daily until disease progression, unacceptable toxicity, or hematopoietic stem cell transplantation. The median treatment duration was 4.1 months (range, 0.1–39.5 months). Of the 174 patients, 21 (12%) received a stem cell transplant following ivosidenib treatment.
Safety and Efficacy
Efficacy was established on the basis of the rate of complete remission plus complete remission with partial hematologic recovery, the duration of complete remission with partial hematologic recovery, and the rate of conversion from transfusion dependence to independence. The complete remission with partial hematologic recovery rate was 32.8% (95% confidence interval [CI]: 25.8%–40.3%). The median time to response was 2 months (range, 0.9–5.6 months), and the median response duration was 8.2 months (95% CI: 5.6–12 months). The complete remission with partial hematologic recovery rates were 24.7% and 8.0%, respectively.
Among the 110 patients who were dependent on red blood cell and/or platelet transfusions at baseline, 41 (37.3%) became independent of red blood cell and platelet transfusions during any 56-day postbaseline period. Of the 64 patients who were independent of both red blood cell and platelet transfusions at baseline, 38 (59.4%) remained transfusion independent during any 56-day postbaseline period.
The most common adverse reactions (≥ 20%) were fatigue, leukocytosis, arthralgia, diarrhea, dyspnea, edema, nausea, mucositis, electrocardiogram QT prolonged, rash, pyrexia, cough, and constipation.
The FDA also approved the RealTime IDH1 Assay on July 20, 2018, for use in selecting patients for treatment with ivosidenib.
The recommended ivosidenib dose is 500 mg orally once daily with or without food until disease progression or unacceptable toxicity. For patients without disease progression or unacceptable toxicity, treatment is recommended for a minimum of 6 months to allow time for clinical response.
For more information, visit FDA.gov. ■