KEY TAKEAWAYS
- The phase I trial aimed to evaluate enasidenib’s tolerability post-HCT and its impact on LFS in mIDH2 AML patients across the multicenter pilot trial.
- The primary objective was to determine safety and tolerability.
- Enasidenib post-HCT maintenance for mIDH2 AML was safe and feasible, with favorable survival, despite frequent treatment adjustments; most complete 2-year maintenance.
About 20% of acute myeloid leukemia (AML) patients harbor somatic mutations in IDH genes, predominantly IDH2 (15%) over IDH1. Prior research noted higher relapse rates post-HCT among mIDH patients.
Amandeep Salhotra and his team spearheaded the study that aimed to present the conclusive outcomes of the multicenter pilot trial (NCT03728335) conducted at City of Hope (COH) and Moffitt Cancer Center, previously summarized with a briefer follow-up at the 2022 ASH meeting.
The main objective was to evaluate enasidenib’s safety and tolerability as post-HCT maintenance in mIDH2 AML patients. The secondary objectives were assessing survival outcomes and relapse rates and examining the 1-year survival free from chronic graft-versus-host disease (cGVHD) and relapse (CRFS).
About 15 recipients of alloHCT with mIDH2 AML (8 at COH, 7 at Moffitt) were enrolled. Eligible patients, regardless of conditioning, had to be in CR at day +30 post-HCT, with ECOG PS ≤2 and adequate marrow function. Those with active acute GVHD (grade ≥2) were excluded. Enasidenib was given at 100 mg/day, following FDA guidelines, from day 50 to day 120 post-HCT, and maintained for 2 years in cycles lasting 28 days each.
The median age was 58 years (range: 24-77), with a male-to-female ratio of 40:60% and 67% Caucasian. Pre-HCT remission status included CR1 in 73%, CR2 in 20%, and measurable residual disease positive in 6%. Cytogenetic risk classification was favorable in 13%, intermediate in 60%, and adverse in 26%. Donors comprised unrelated (53%), related (20%), or haploidentical (26%). Most patients (80%) underwent reduced-intensity conditioning, receiving PBSCs as graft source. GVHD prophylaxis was PTCy (60%) or tacrolimus-based.
At the last data cutoff, 12 out of 15 (80%) patients completed all 24 planned cycles. Reasons for maintenance discontinuation included toxicity, loss of follow-up, and physician discretion. The median follow-up duration was 23.6 months (range: 20.0-33.4). Adverse events (AEs) of all grades in the first 2 cycles and grade ≥3 AEs for subsequent cycles were collected. In the initial 2 cycles, grade ≥3 AEs were mainly hematologic, including lymphopenia (46%; n=7), neutropenia (13%; n=2), anemia (53%; n=8), and thrombocytopenia (33%; n=5).
The non-hematologic AEs were grade 1-2 nausea (60%; n=9) and vomiting/diarrhea (26%; n=4), and the 1-year and 2-year overall survival and LFS were 100%, resulting in high 1-year and 2-year CRFS of 93% and 87%, respectively.
The study concluded that post-HCT maintenance therapy utilizing enasidenib is safe and feasible, yielding highly favorable survival outcomes in mIDH2 AML. Although treatment delays and dose reductions were frequent, most patients successfully completed their 2-year maintenance regimen. Research was funded by the City of Hope Medical Center.
Source: https://tandem.confex.com/tandem/2024/meetingapp.cgi/Paper/23931
Clinical Trial: https://clinicaltrials.gov/study/NCT03728335
Salhotra A,Yang D, Mokhtari S, et al. “Multicenter Pilot Clinical Trial of Enasidenib As Maintenance Therapy after Allogeneic Hematopoietic Cell Transplantation (alloHCT) in Patients with Acute Myeloid Leukemia (AML) Carrying IDH2 Mutations.” Presented at TCT-ASTCT-CIBMTR 2024 (February 21-24, 2024) | Henry B. González Convention Center, San Antonio, Texas.
