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Enasidenib Safe, Well Tolerated As Maintenance After Stem Cell Transplantation for IDH2-Mutated Myeloid Malignancies

Key findings

  • The primary objective of this phase 1, multicenter, dose-finding study was to define the recommended phase 2 dose of enasidenib as maintenance therapy following hematopoietic cell transplantation for IDH2-mutated myeloid malignancies
  • Enasidenib was well tolerated at the doses studied, 50 and 100 mg/day, and 100 mg was deemed the recommended phase 2 dose
  • 11 of the 19 patients completed all 12 planned cycles, and only three patients stopped enasidenib because of adverse events deemed at least possibly related to treatment
  • Grade 3 or higher toxicities were infrequent, with the most common being cytopenias
  • Transient dose interruptions were required for eight patients, but dose reductions to 50 mg/day allowed most patients to continue and tolerate treatment

Enasidenib is FDA-approved for treatment of relapsed/refractory IDH2-mutated acute myeloid leukemia (AML). Researchers at Mass General Cancer Center now show in Blood Advances showing enasidenib is safe and well tolerated as maintenance therapy following allogeneic hematopoietic cell transplantation for IDH2-mutated myeloid malignancies.

The authors are Amir T. Fathi, MD, program director of the Center for Leukemia at Mass General Cancer Center, Yi-Bin Chen, MD, director, Hematopoietic Cell Transplant & Cell Therapy, Zachariah DeFilipp, MD, director of clinical research in the Bone Marrow Transplant Program, Areej El-Jawahri, MD, an oncologist in the Division of Hematology and Oncology, and colleagues.


In the multi-center study, 19 adults with mutant IDH2 mutations were started on enasidenib maintenance between 30 and 90 days after HCT (median, 55 days; range, 37–90). Their median age was 63.

Eight patients had newly diagnosed AML, seven had AML with myelodysplasia-related changes, two had AML arising from antecedent myeloproliferative neoplasms and two had myelodysplastic syndrome with excess blasts.

Enasidenib was to be taken once daily for twelve 28-day cycles. The period for evaluation of dose-limiting toxicity was the first cycle.


Three patients were enrolled at 50 mg/day, followed by six at 100 mg/day. No dose-limiting toxicities were detected. Pursuant to the protocol 10 additional patients were enrolled at 100 mg/day, which has been deemed the recommended phase 2 dose.


Grade 3 adverse events considered possibly, probably or definitely treatment-related were anemia (n=2 patients), bilirubinemia (n=1), coronary ischemia (n=1), fatigue (n=1) and hyponatremia (n=1). One case of grade 4 treated-related neutropenia occurred.

Treatment Persistence

Notable observations about treatment persistence were:

  • Dose interruptions—Nine separate episodes in eight patients, six cases of treatment-related toxicity and three of graft-versus-host disease
  • Dose reductions to 50 mg—Required by six patients, none during the first cycle; all continued treatment
  • Number of patients who received all 12 planned cycles—11


Accurate estimations of activity require larger studies, but the cumulative incidence of relapse was 16% and estimated progression-free survival and overall survival at two years were 69% and 74%, respectively.

Although numbers are small and assessment of clinical activity requires larger studies, outcomes in this phase 1 study were encouraging and compared favorably to historical data.

Learn about the Center for Leukemia

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