Progress in Targeted Therapy for Acute Myeloid Leukemia

Biologic subtypes of acute myeloid leukemia (AML) are defined by mutations in pathogenically relevant genes, including IDH1 (isocitrate dehydrogenase 1), which portends an adverse clinical outcome. Now, in a phase 3 multicenter, industry-sponsored trial, investigators evaluated the IDH1 inhibitor ivosidenib (IVO) in previously untreated patients with IDH1-mutated AML who were not eligible for intensive induction chemotherapy.

A total of 146 patients were randomized to receive azacitidine (AZA) intravenously or subcutaneously for 7 days of 28-day cycles plus either oral IVO (500 mg/day) or placebo. Treatment continued until progression or unacceptable toxicity. The primary end point was event-free survival (EFS), defined as absence of complete remission by week 24, relapse, or death from any cause.

The 12-month EFS rate was significantly higher in the IVO/AZA group than the placebo/AZA group (37% vs. 12%; hazard ratio, 0.33; P=0.002). Median overall survival was also significantly higher in the IVO/AZA group (24.0 vs. 7.9 months; P=0.001). Toxicities were similar in the two groups, aside from a higher rate of differentiation syndrome in the IVO/AZA group (14% vs. 8%).