AGILE: Long-term results of ivosidenib vs placebo in IDH1-mutated newly diagnosed AML

Ivosidenib was approved by the U.S. Food and Drug Administration in 2022 in combination with azacitidine for patients with IDH1-mutated newly diagnosed acute myeloid leukemia (AML), and by the European Commission in 2023 for those ineligible for standard intensive chemotherapy, based on the phase III AGILE study (NCT03173248). The AML Hub previously reported findings from AGILE. 

Montesinos et al. published a post hoc analysis reporting long-term results from AGILE evaluating the efficacy and safety of ivosidenib + azacitidine vs placebo + azacitidine in patients with IDH1-mutated newly diagnosed AML in Blood Advances.

Briefly, 148 patients were randomized to receive either 500 mg ivosidenib (n = 73) or placebo (n = 75) once daily, with each group receiving 75 mg/m² azacitidine for 7 days in 28-day cycles. The post hoc analysis endpoints included overall survival, hematological responses, and transfusion dependence. The median follow-up was 28.6 months.

Key learnings

The median OS was longer in the ivosidenib + azacitidine vs placebo + azacitidine arm (29.3 months vs 7.9 months; HR, 0.42; 95% CI, 0.27–0.65; p < 0.0001).

In the ivosidenib + azacitidine arm, hematologic recovery was faster and more durable, with a higher proportion of patients achieving transfusion independence (53.8% vs 17.1%; p = 0.0004) compared with the placebo + azacitidine arm.

Of the MRD-evaluable patients in the ivosidenib + azacitidine arm (n = 33), 30.3% achieved MRD-negativity by D1 C14. In patients stratified by reduction of baseline mutations, the estimated OS was longer in those with MRD <1% vs MRD ≥1% (p = 0.03).

The ivosidenib + azacitidine combination was well tolerated with robust clinical benefit and sustained survival in patients with IDH1-mutated newly diagnosed AML who were ineligible for intensive chemotherapy.