Trial of Enasidenib Maintenance Post-Allogeneic Hematopoietic Cell Transplantation in Patients with IDH2-Mutated Acute Myeloid Leukemia.

The relapse rate at 1 year is approximately 30% in acute myeloid leukemia (AML) patients with an IDH2 mutation who undergo allogeneic hematopoietic cell transplantation (alloHCT). We designed a 2-center, open-label, single-arm pilot trial to investigate the safety and tolerability of enasidenib as post-HCT maintenance in AML patients carrying the IDH2 mutation (Clinical Trials.gov NCT03728335). Recipients of first alloHCT who had AML with an IDH2 mutation at the time of diagnosis were eligible for maintenance if in complete remission (CR) at day +30 post-HCT, had an Eastern Cooperative Oncology Group Performance Scale score ≤2, and adequate hematopoietic recovery. Patients with grade ≥II acute graft-versus-host disease (GVHD) were excluded. Enasidenib was given at a dose of 100 mg/day between days 50 and 120 post-HCT for 2 years in 28-day cycles. The primary objective was to evaluate the safety and tolerability of enasidenib as post-HCT maintenance therapy, and secondary objectives were to assess clinical outcomes. A total of 15 patients were enrolled in this pilot study, with a median age of 58 years and median follow-up of 24 months. Pretransplantation remission status was first CR (CR1) in the majority of patients (73%), and 26.7% of the patients were at adverse risk for AML by 2022 European LeukemiaNet classification. Most patients (80%) received reduced-intensity conditioning from an HLA-matched related or unrelated donor (73%), and 60% received post-transplantation cyclophosphamide-based GVHD prophylaxis. Study patients completed a median of 24 (range, 1 to 24) cycles of enasidenib. Enasidenib maintenance therapy was well tolerated; the discontinuation rate was 20%, and 12 patients completed 2-year maintenance of enasidenib. Grade ≥3 adverse effects were mainly hematologic and gastrointestinal toxicities. The 2-year overall survival and leukemia-free survival rates were 100%, and the 2-year chronic GVHD (cGVHD)-free and relapse-free survival rate was 80%. Post-HCT enasidenib maintenance therapy was safe and well-tolerated, resulting in favorable relapse control and survival outcomes in AML patients carrying an IDH2 mutation. A phase 2 multicenter study investigating the effectiveness of enasidenib maintenance as a relapse-prevention strategy after alloHCT is ongoing.