Maintenance therapy with the oral histone deacetylase (HDAC) inhibitor chidamide (tucidinostat) plus azacitidine (Vidaza) generated a 3-year overall survival (OS) rate of 91.4% (95% CI, 87.2%-95.6%) in patients with high-risk acute myeloid leukemia (AML) who had undergone allogeneic hematopoietic stem cell transplantation (allo-HSCT), according to updated data from a phase 2 study (ChiCTR2300067593) presented at the 2026 EHA Congress.1
At a data cutoff of January 8, 2026, and a median follow-up of 38.8 months (range, 12.6-56.5), patients (n = 52) achieved a 3-year relapse-free survival (RFS) rate of 90.4% (95% CI, 86.3%-94.5%) and a 3-year cumulative incidence of relapse (CIR) rate of 7.7% (95% CI, 2.6%-9.0%). The non-relapse mortality (NRM) rate was 1.9% (n = 1).
“The results of our study suggested that dual epigenetic targeting maintenance treatment with chidamide plus azacitidine has an acceptable toxicity profile and might potentially be effective to prevent relapse after allo-HSCT,” lead study author Xiao-Hui Hu, MD, of The First Affiliated Hospital of Soochow University in Suzhou, China, and coauthors wrote in a poster.
How was the phase 2 study designed?
The multicenter, open-label, prospective phase 2 study enrolled patients with high-risk AML who had undergone allo-HSCT across 3 hospitals in China between November 2021 and October 2024. Maintenance could begin as early as 3 months after transplantation, with a median start time of 4.6 months (range, 2.8-9.1), and all patients were required to be in complete remission before each cycle.
Chidamide was administered orally at 5 mg once daily for 5 days in combination with azacitidine at 75 mg/m² given subcutaneously once daily for 5 days. A total of 6 cycles was recommended, and the median number of cycles given was 6 (range, 1-6).
Initial results from the study were published in Clinical Epigenetics in 2025.2
Chidamide Plus Azacitidine Maintenance in High-Risk AML After Allo-HSCT: Key Findings
- At a median follow-up of 38.8 months, the 3-year OS and RFS rates were 91.4% and 90.4%, respectively.
- The 3-year cumulative incidence of relapse was 7.7%, with a non-relapse mortality rate of 1.9%.
- Hematologic toxicity (86.5%) was the most common adverse effect, and no grade 3 or higher adverse effects were reported.
What were the key baseline characteristics?
The median patient age was 39 years (range, 17-60), and the population was split between male (48.1%) and female (51.9%) patients.1 Most patients had de novo AML (86.5%), whereas 13.5% had secondary AML. At the time of transplantation, 55.8% of patients were in first complete remission, 25.0% were in second complete remission, and 19.2% had no remission; half of the patients (50.0%) had primary refractory or relapsed disease.
According to 2022 European LeukemiaNet criteria, 65.4% of patients had adverse-risk disease, 30.8% had favorable-risk disease, and 3.8% had intermediate-risk disease, while 53.8% harbored epigenetic alterations. Donors were haploidentical in 55.8% of patients, unrelated in 30.8%, and matched siblings in 13.5%.
What did the safety analysis show?
The most common adverse effect (AE) was hematologic toxicity, which occurred in 86.5% of patients (n = 45/52); most patients experienced only mild bone marrow suppression that was managed with outpatient hematopoietic growth factors or observation without medication. Eleven patients (21.2%) received platelet transfusions, and 1 patient (1.9%) received red blood cell transfusions. No grade 3 or higher AEs were reported, and investigators noted that all AEs were tolerable and did not affect subsequent therapy.
Among 6 patients who developed infections, 4 had pulmonary infections, including 1 case of Epstein-Barr viremia reactivation. One patient had an intestinal infection, and 1 had cytomegaloviremia. Chronic graft-vs-host disease (GVHD) developed in 28.8% of patients, and acute GVHD was observed in 1 patient; one patient died of lung GVHD. Four patients relapsed: 1 declined intensive treatment and died, 2 relapsed after a second transplantation and died, and one1remained alive in remission after a second transplantation.
References
- Wu YX, Wu DP, Xue SL, Hu XH. Updated results from the phase II study of dual epigenetic targeting with chidamide and azacitidine in patients with high-risk acute myeloid leukemia after allo-HSCT. Presented at: 2026 EHA Congress; June 11-14, 2026; Stockholm, Sweden. Abstract PF393.
- Wu YX, Wu DP, Xue SL, et al. Phase II study of dual epigenetic targeting with chidamide and azacitidine in patients with high-risk acute myeloid leukemia after allo-HSCT. Clin Epigenetics. 2025;17(1):171. doi:10.1186/s13148-025-01987-w