On May 2, the U.S. Food and Drug Administration (FDA) expanded its approval of ivosidenib (Tibsovo) to include newly diagnosed acute myeloid leukemia (AML) with a susceptible IDH1 mutation, as detected by an FDA-approved test, in patients who are at least 75 years old or who have comorbidities that preclude the use of intensive induction chemotherapy. The drug was previously approved in adult patients with relapsed or refractory AML.
Approval was based on the open-label, single-arm, multicenter AG120-C-001 clinical trial of single-agent ivosidenib for newly diagnosed AML with an IDH1 mutation detected by the -Abbott RealTime IDH1 Assay. Patients enrolled were at least 75 years old or met at least 1 of the following criteria: baseline Eastern Cooperative Oncology Group performance status ≥ 2, severe cardiac or pulmonary disease, hepatic impairment with bilirubin > 1.5 times the upper limit of normal, or creatinine clearance < 45 mL/min. The 28 patients treated had a median age of 77 years (range = 64–87 years), and 22 (79%) had therapy-related AML or AML with myelodysplasia-related changes.
Ivosidenib was administered orally at a dose of 500 mg daily until disease progression, development of unacceptable toxicity, or hematopoietic stem cell transplantation. Of the 28 patients, 2 underwent stem cell transplantation following ivosidenib.
Efficacy was based on the rate of complete remission or complete remission with partial hematologic recovery, the duration of these remissions, and the conversion rate from transfusion dependence to transfusion independence. A total of 12 (42.9%) of the 28 achieved complete remission with or without partial hematologic recovery (95% confidence interval [CI] = 24.5–62.8), and 7 (41.2%) of the 17 transfusion-dependent patients achieved transfusion independence lasting at least 8 weeks.
The adverse reactions that occurred in at least 25% of patients were diarrhea, fatigue, edema, decreased appetite, leukocytosis, nausea, arthralgia, abdominal pain, dyspnea, differentiation syndrome, and myalgia. Prescribing information contains a boxed warning alerting health-care professionals and patients about the risk of differentiation syndrome, which may be life-threatening or fatal.
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. ■