Enasidenib appears to offer some clinical promise among elderly patients with IDH2-mutant relapsed or refractory acute myeloid leukemia (AML), according to research published in Blood.

Real-world data suggest that patients with relapsed or refractory AML have poor outcomes; improved novel treatments are therefore essential in these cases. Previous data have also shown that as many as 1 in 5 patients may present with IDH2-mutated disease.

Enasidenib is a selective inhibitor of 2-HG production, which is dysregulated in those with IDH2 mutations. The drug was approved by the US Food and Drug Administration for the treatment of relapsed/refractory AML in the presence of an IDH2 mutation; this occurred after the publication of a single-arm pivotal phase 1/2 study.

Continue Reading

For this phase 3 randomized trial, researchers compared the safety and efficacy of enasidenib with conventional care regimens (CCRs) among patients with IDH2-mutated relapsed or refractory AML.

Overall, 319 patients were enrolled, among whom 158 were randomly assigned to receive enasidenib and 161 were assigned to the CCR group, though 1 and 20 patients, respectively, did not receive randomized treatment. In the overall cohort, the median age was 71 years, 41.4% of patients were female sex, and 30.7% of patients had secondary disease.

Analysis showed that the median overall survival was 6.5 months with enasidenib vs 6.2 months in the CCR group (hazard ratio [HR], 0.86; P =.23), missing the study’s primary endpoint.

Patients in the enasidenib group did, however, have improved event-free survival (median, 4.9 months vs 2.6 months in the CCR group; P =.008), time to treatment failure (HR, 0.53; P <.001), overall response rate (40.5% vs 9.9%, respectively; P <.001), hematologic improvement (42.4% vs 11.2%, respectively), and red blood cell–transfusion independence (31.7% vs 9.3%, respectively).

“Results from this randomized, phase 3 study support enasidenib as an appropriate oral outpatient treatment for patients with mutant-IDH2 [relapsed/refractory] AML,” the authors wrote in their report.

Disclosure: Some study authors declared affiliations with biotech, pharmaceutical, or device companies. Please see the original reference for a full list of authors’ disclosures. 


de Botton S, Montesinos P, Schuh AC, et al. Enasidenib vs conventional care in older patients with late-stage mutant-IDH2 relapsed/refractory AML: a randomized phase 3 trial. Blood. 2023;141(2):156-167. doi:10.1182/blood.2021014901