The U.S. Food and Drug Administration (FDA) has approved TIBSOVO (ivosidenib) for the treatment of relapsed or refractory adult acute myeloid leukemia (AML) with IDH1 gene mutations.
The approval is based on an open-label, single-arm, multicenter clinical trial (AG120-C-001, NCT02074839) that enrolled 174 adult patients with relapsed or refractory AML who had been confirmed to have IDH1 mutations in the Abbott RealTime IDH1 trial (an FDA trial used to select AML patients for ivosidenib treatment). Ivosidenib is administered orally at a starting dose of 500 mg daily. Dosage is discontinued if the patient experiences persistent disease progression, excessive drug toxicity, or requires hematopoietic stem cell transplantation. The median duration of treatment is 4.1 months (range 0.1–39.5 months). Of the 174 patients, 21 (12%) underwent stem cell transplantation after treatment with ivosidenib.
Efficacy was determined based on the duration of CR (complete response) + CRh (complete response with partial hematologic improvement) and the rate of conversion from transfusion dependence to independence. The trial demonstrated a CR+CRh rate of 32.8% (95% confidence interval: 25.8%–40.3%). The median time to response was 2 months (range 0.9–5.6 months), and the median duration of response was 8.2 months (95% confidence interval: 5.6–12 months). The CR and CRh rates were 24.7% (95% confidence interval: 18.5%, 31.8%) and 8.0% (95% confidence interval: 4.5%, 13.1%), respectively. Of the 110 patients who were dependent on red blood cell (RBC) and platelet transfusions at baseline, 41 (37.3%) were no longer required to receive RBC and platelet transfusions within 56 days after baseline. Of the 64 patients who were not dependent on RBC and platelet transfusions at baseline, 38 (59.4%) still did not require transfusions within 56 days after baseline.
The most common adverse reactions (≥20%) were fatigue, leukocytosis, arthralgia, diarrhea, dyspnea, edema, nausea, mucositis, prolonged QTc interval on ECG, rash, fever, cough, and constipation.
The recommended dose of ivosidenib is 500 mg orally daily, taken with food. Discontinue use if the condition continues to worsen or if the drug causes excessive toxicity. Treatment is recommended for at least 6 months.
