A recent phase 3 trial in patients with relapsed/refractory (R/R) IDH2-mutated acute myeloid leukemia (AML) evaluated treatment with enasidenib compared with a conventional care regimen (CCR), but the primary endpoint was not met. However, meaningful benefits were seen for several secondary endpoints with enasidenib. The results of the trial were reported in the journal Blood.

The open-label trial (ClinicalTrials.gov Identifier: NCT02577406) included patients who were ≥60 years of age who had IDH2-mutated R/R AML and who had been treated with 2 to 3 prior AML-directed therapies. Patients initially received a CCR, which could include azacitidine, intermediate-dose cytarabine, low-dose cytarabine, or best supportive care. After the initial CCR, patients were randomly assigned 1:1 to receive either enasidenib (100 mg/d) or a CCR. Overall survival (OS) was the primary endpoint.

A total of 158 patients were randomly assigned to the enasidenib arm and 161 patients to the CCR arm. The median patient ages were 72 years (range, 60-85) in the enasidenib arm and 71 years (range, 60-86) in the CCR arm. In the enasidenib arm, 7.6% of patients had had 2 prior relapses, and in the CCR arm, 14.3% of patients did. Patients in the enasidenib arm had a median treatment duration of 142 days (range, 3-1270). In the CCR arm, the median treatment duration was 36 days (range, 1-1166).

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In the intention-to-treat analysis, the enasidenib arm had a median OS of 6.5 months, compared with 6.2 months in the CCR arm (hazard ratio [HR], 0.86; 95% CI, 0.67-1.10; P =.23). Estimated 1-year OS rates were 38% in the enasidenib arm and 26% in the CCR arm.

The median event-free survival was 4.9 months in the enasidenib arm and 2.6 months in the CCR arm (HR, 0.68; 95% CI, 0.52-0.91; P =.008). The median time to treatment failure was also longer with enasidenib than with CCR (4.9 months vs 1.9 months; HR, 0.53; 95% CI, 0.41-0.67; P <.0001).

The overall response rate was 40.5% in the enasidenib arm and 9.9% in the CCR arm (P <.001). Hematologic improvement rates were 42.4% in the enasidenib arm and 11.2% in the CCR arm (P <.001). The rates of red blood cell transfusion independence were 31.7% for the enasidenib arm and 9.3% for the CCR arm.

The investigators considered the safety profile for enasidenib to be acceptable and consistent with its safety profile in a pivotal phase 1/2 study. They concluded that the primary endpoint of OS was not met in this study, but enasidenib was associated with benefits in event-free survival, time to treatment failure, response, and transfusion requirements.

Disclosures: This research was supported by Celgene. 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.


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. Published online June 17, 2022. doi:10.1182/blood.2021014901

This article originally appeared on Hematology Advisor