Combining oral ivosidenib with subcutaneous azacitidine leads to durable responses and is well-tolerated in patients with acute myeloid leukemia (AML), according to research in the Journal of Clinical Oncology.

Approximately 20% of AMLs have mutations in isocitrate dehydrogenase 1 and 2 (IDHI1/2). Ivosidenib is a mutant IDHI1 inhibitor, approved to treat IDH1-mutant AML. The authors of the phase 1b dose-finding and dose-expansion study sought to determine the safety clinical activity of ivosidenib plus azacitidine, a hypomethylating agent, in patients with newly diagnosed IDH1-mutant AML who are ineligible for intensive chemotherapy.

The study enrolled 23 patients with a median age of 76 years. Patients received 500 mg of oral ivosidenib once daily plus 75 mg/m2/d subcutaneous azacitidine on days 1 to 7 for 28-day cycles. At data cutoff 10 patients remained on treatment.

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All patients experienced at least 1 grade 3 or greater adverse event; however, there were no dose-limiting toxicities. The most common adverse events were thrombocytopenia, nausea, diarrhea, anemia, constipation, febrile neutropenia, pyrexia, and vomiting.

The 30-day mortality rate was 0%, and the 60-day mortality rate was 4% (1 death); 2 patients required dose reduction because of adverse events with ivosidenib, and 5 patients required dose reductions with azacitidine. More than half of the study patients required hospitalization during the study because of adverse events. The authors concluded that the safety profile in the study was consistent with the safety profile of azacitidine monotherapy.

The overall response rate (ORR) in the study was 78.3%, with a median treatment duration of 15.1 months. Complete remission was reported in 61% of patients. The median overall survival was not estimable at 16.1 months of follow-up, but the 12-month survival was estimated as 82%.

These study results show promise for the combination treatment compared to study results of azacitidine alone. The conclusions may be limited by the small sample size and eligibility criteria, which may not represent the general population of AML patients ineligible for intensive chemotherapy. 

The authors conclude that ivosidenib plus azacitidine is well-tolerated and induces deep, durable remissions in elderly patients with IDHI1-mutant AML who cannot undergo intensive chemotherapy.

Disclosures: Some authors have declared affiliations with or received grant support from the pharmaceutical industry. Please refer to the original study for a full list of disclosures.


DiNardo CD, Stein AS, Stein EM, et al. Mutant isocitrate dehydrogenase 1 inhibitor ivosidenib in combination with azacitidine for newly diagnosed acute myeloid leukemia. J Clin Oncol. Published online October 29, 2020. doi:10.1200/JCO.20.01632