July 20, 2018—Today, the U.S. Food and Drug Administration (FDA) approved the use of ivosidenib, an isocitrate dehydrogenase-1 (IDH1) inhibitor, for the treatment of adult patients with relapsed/refractory acute myeloid leukemia (AML) who have are IDH1-mutation positive. This is the first IDH1 inhibitor approved for patients with AML.
“[Ivosidenib] is a targeted therapy that fills an unmet need for patients with relapsed or refractory AML who have an IDH1 mutation,” said Richard Pazdur, MD, director of the FDA’s Oncology Center of Excellence in a press release. “The use of [ivosidenib] is associated with a complete remission in some patients and a reduction in the need for both red cell and platelet transfusions.”
Today’s approval is based on results from a single-arm phase I trial (NCT02074839) of 174 adult patients with relapsed or refractory AML harboring an IDH1 mutation. The rate of complete remission (CR), the primary endpoint, was 24.7% (N = 43) while the rate of CR with partial hematologic improvement (CRh) was 8% (n = 14). Overall, the median duration of CR/CRh was 8.2 months. Among patients who achieved a CR/CRh, the median time to best response was 2.0 months.
Common adverse events (AEs) occurring in ≥20% of patients included fatigue, leukocytosis, arthralgia, diarrhea, dyspnea, edema, nausea, mucositis, QT prolongation, rash, pyrexia, cough and constipation. The most common high-grade AEs included differentiation syndrome (10%), leukocytosis (10%) and electrocardiogram QT prolonged (7%).
The FDA has stressed that ivosidenib contains a boxed warning for differentiation syndrome, an AE which can be fatal if left untreated. Symptoms of differentiation syndrome may include fever, dyspnea, acute respiratory distress, radiographic pulmonary infiltrates, pleural or pericardial effusions, rapid weight gain, peripheral edema, or hepatic/renal/multi-organ dysfunction. At first suspicion of symptoms, doctors should treat patients with corticosteroids and monitor patients closely until symptoms go away. Full prescribing information for ivosidenib can be found here.
Jonathan A. Bell
Published Online: Friday, July 20, 2018