Two-year data from the AGILE trial demonstrated that the addition of ivosidenib to azacitidine improved overall survival (OS) among patients with newly-diagnosed, IDH1-mutated acute myeloid leukemia (AML). The updated data were presented at the SOHO 2023 Annual Meeting.

The double-blind, phase 3 AGILE study ( identifier: NCT03173248) randomly assigned patients with IDH1-mutated AML to receive ivosidenib plus azacitidine or placebo plus azacitidine as first-line treatment.

Previously, the median OS was reported as 24 months with ivosidenib compared with 7.9 months with placebo (hazard ratio [HR], 0.44; 95% CI, 0.27-0.73; P =.001).

Continue Reading

This report focused on 2-year follow-up data with a data lock of June 2022. The median follow-up was 28.6 months and included data from 148 patients. The median duration of treatment with ivosidenib plus azacitidine was 10.8 months, whereas the median duration was 3.2 months with placebo plus azacitidine.

OS remained significantly longer among patients treated with ivosidenib, with a median of 29.3 months compared with 7.9 months with placebo (HR, 0.42; 95% CI, 0.27-0.65; P <.0001). The 1-year OS was 62.9% and 38.3% in the ivosidenib and placebo groups, respectively, the 2-year OS was 53.1% and 17.4%, and the 3-year OS was 41.0% and 11.9%.

Absolute hemoglobin levels increased from a mean baseline level of 88.8 g/L through cycle 8 of ivosidenib plus azacitidine treatment, then plateaued at approximately 120 g/L and remained stable for the remaining period.

Of the approximate 54% of patients who were red blood cell (RBC) or platelet transfusion-dependent at baseline, 53.8% achieved transfusion independence with ivosidenib compared with 17.1% of patients who received placebo (odds ratio, 6.2; 95% CI, 2.0-19.1; P =.0004). In the ivosidenib and placebo groups, 70.6% and 67.6% of patients, respectively, who were transfusion independent at baseline remained so during the study.

The safety profile of the combination was maintained with long-term treatment. There were 18.1% of patients who required an ivosidenib dose reduction and 8.1% who required a placebo dose reduction due to treatment-emergent adverse events (TEAEs). Treatment discontinuation due to TEAEs were similar between groups, at 26.4% with ivosidenib and 25.7% with placebo.

The most common grade 3-4 hematologic TEAEs in the ivosidenib group were neutropenia, febrile neutropenia, anemia, and thrombocytopenia. The most common nonhematologic TEAEs of grade 3 or higher severity included pneumonia and infections.

“Long-term follow-up date support the superior efficacy of ivosidenib plus azacitidine versus placebo plus azacitidine in patients with newly diagnosed IDH1-mutated AML,” the authors concluded in their poster. Additionally, they noted the combination results in durable responses.

Disclosures: The study was supported by Agios Pharmaceuticals, Inc. Please see the original reference for a full list of disclosures.

de Botton S, Montesinos P, Polo SV, et al. Ivosidenib + azacitidine vs placebo + azacitidine in patients with newly‑diagnosed acute myeloid leukemia: updated long‑term efficacy and safety results from the AGILE study. Presented at: the Eleventh Annual Meeting of the Society of Hematologic Oncology (SOHO); September 6-9, 2023. AML-469.