Site Editor

Rebecca Olin, MD, MS


Phase III AGILE Trial: Combining Ivosidenib With Azacitidine in IDH1-Mutated AML

By: Vanessa A. Carter, BS
Posted: Wednesday, June 1, 2022

The phase III AGILE trial, performed by Hartmut Döhner, MD, of Ulm University Hospital, Germany, and colleagues, evaluated whether the addition of ivosidenib to azacitidine in patients with IDH1-mutated acute myeloid leukemia (AML) might improve outcomes. The results of their trial concluded that the combination therapy significantly improved response, event-free survival, and overall survival when compared with placebo plus azacitidine. These findings were published in The New England Journal of Medicine.

“Ivosidenib and azacitidine showed significant clinical benefit as compared with placebo and azacitidine in this difficult-to-treat population,” concluded the study authors. “This clinical benefit is supported by favorable health-related quality of life, incidences of transfusion independence, and the expected constellation of adverse events associated with treatment for acute leukemia.”

This phase III, double-blind, global trial enrolled 146 patients with newly diagnosed, IDH1-mutated AML who were ineligible for intensive induction chemotherapy. Participants were randomly assigned to receive azacitidine with either ivosidenib (n = 72) or placebo (n = 74).

The median follow-up was 12.4 months, and event-free survival was observed to be significantly longer among patients on ivosidenib and azacitidine versus those on placebo and azacitidine (P = .002). The estimated probability that any patient would remain event-free at 12 months was also higher with ivosidenib/azacitidineversusplacebo/azacitidine, with rates of 37% and 12%, respectively. Furthermore, the median overall survival of individuals given ivosidenib and azacitidine was increased by nearly threefold when compared with those given placebo (24.0 vs. 7.9 months; P = .001).

The most common grade 3 or higher adverse event was febrile neutropenia, affecting 28% and 34% of individuals treated with ivosidenib plus azacitidine and placebo plus azacitidine, respectively; the ivosidenib-treated group experienced a higher incidence of bleeding events (41% vs. 29%). Of note, patients who received placebo had a much higher incidence of infection of any grade (49%) than those who received the ivosidenib combination (28%).

Disclosure: For full disclosures of the study authors, visit

By continuing to browse this site you permit us and our partners to place identification cookies on your browser and agree to our use of cookies to identify you for marketing. Read our Privacy Policy to learn more.