Ivosidenib Plus Azacitidine Approved in Newly Diagnosed AML

The U.S. Food and Drug Administration (FDA) has approved ivosidenib in combination with azacitidine for newly diagnosed IDH1-mutated acute myeloid leukemia (AML), as detected by an FDA-approved test in adults aged 75 years or older or those who have comorbidities that preclude use of intensive induction chemotherapy.

The approval was based on data from a trial that randomized patients with newly-diagnosed IDH1-mutated AML to receive ivosidenib 500 mg daily or matched placebo once daily on days 1-28 in combination with azacitidine 75 mg/m² on days 1-7 or days 1-5 and 8-9 of each 28-day cycle.

Other inclusion criteria included baseline Eastern Cooperative Oncology Group performance status of 2, severe cardiac or pulmonary disease, hepatic impairment with bilirubin >1.5 times the upper limit of normal, creatinine clearance <45 mL/min, or other comorbidities.

Event-free survival events occurred in 65% of patients assigned to receive ivosidenib plus azacitidine compared with 84% of the placebo/azacitidine arm (hazard ratio [HR]=0.35; 95% CI, 0.17-0.72; P=.0038). The median overall survival was 24.0 months for ivosidenib plus azacitidine compared with 7.9 months in the placebo arm (HR=0.44; 95% CI, 0.27-0.73; P=.0010).

Complete response was also more than doubled in the ivosidenib plus azacitidine arm compared with placebo (47% vs 15%).

The most common adverse reactions associated with ivosidenib monotherapy or in combination with azacitidine (≥25% in any trial) were diarrhea, fatigue, edema, nausea, vomiting, decreased appetite, leukocytosis, arthralgia, dyspnea, abdominal pain, mucositis, rash, electrocardiogram QT prolonged, 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.

Source: FDA Press Release, May 2022