Enasidenib monotherapy leads to positive and durable treatment outcomes among older patients with previously untreated mutant-IDH2(mIDH2) acute myeloid leukemia (AML) who are not candidates for standard therapy, according to findings presented at the 23rd Annual Congress of the European Hematology Association in Sweden.1

Evidence from previous studies have demonstrated that enasidenib — an oral inhibitor of mIDH2 proteins — leads to good overall response rates (ORR) and overall survival (OS) among patients with relapsed/refractory AML. Investigators sought to evaluate its efficacy among older patients with untreated AML, a population that is associated with poor therapeutic outcomes. 

In this open-label phase 1/2 study (ClinicalTrials.gov Identifier: NCT01915498), researchers enrolled 345 patients aged 60 years and older with AML. Patients were assigned to the phase 1 dose-escalation study where they received enasidenib 50 mg/day to 650 mg/day. All patients in the phase 1 expansion and phase 2 study received enasidenib 100 mg daily in consecutive 28-day cycles. The median age of participants was 77 years, 26% had National Comprehensive Cancer Network poor-risk cytogenetics, and 56% had an antecedent hematologic disorder.

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Overall, 39 patients had untreated mIDH2AML and were evaluable for this analysis. The ORR was 30.8%, of which 18% (7) of patients achieved a complete response (CR) and 5% (2) achieved a partial response; the estimated median durations of CR or any other response was not reached. The time to first response was 1.9 months and the best response was at 3.7 months. Stable disease was observed in 49% (19) of patients and disease progression was seen in 1 patient. 

After a median follow up of 8.4 months, the median OS was 11.3 months (95% CI, 5.7-15.1) with a median event-free survival of 5.7 months (95% CI, 2.8-16.0). The median OS among responders was not evaluable. 

The most frequently observed adverse events (AEs) included fatigue, decreased appetite, nausea, and constipation; the most frequently reported treatment-related AEs were hyperbilirubinemia and nausea. Serious AEs were IDH differentiation syndrome and tumor lysis syndrome, which occurred in 5 and 2 patients, respectively. 

The authors concluded that “these results suggest enasidenib may benefit older adults with mIDH2 AML who are not fit to receive cytotoxic regimens. Enasidenib is under study in a similar AML patient population in the Beat AML Master Trial [ClinicalTrials.gov Identifier:NCT03013998].”


  1. Pollyea DA, Tallman MS, de Botton S, et al. Enasidenib monotherapy is effective and well-tolerated in patients with previously untreated mutant-IDH2 (MIDH2) acute myeloid leukemia (AML). Oral presentation at: 2018 European Hematology Association 23rd Annual Congress; June 2018; Stockholm, Sweden.