Chidamide Plus Azacitidine Maintenance Demonstrates Promising Activity for Preventing Relapse After alloHSCT for Patients With High-Risk AML
Key Clinical Summary
- Design/Population: A prospective, open-label phase 2 trial (ChiCTR2300067593) enrolled 48 patients with high-risk acute myeloid leukemia (AML) between November 2021 and March 2024 to evaluate chidamide + azacitidine (CHI-AZA) maintenance following allogeneic hematopoietic stem cell transplantation (alloHSCT). Treatment began ≥3 months post-transplant for up to 6 cycles.
- Key Outcomes: At 26.9 month median follow-up, 2-year CIR was 8.4% (95% CI, 4.4 to 12.4); RFS 91.6% (95% CI, 87.6 to 95.6); OS 97.9% (95% CI, 95.8 to 100). Relapse occurred in 4 patients. No grade ≥ 4 AEs were reported; GVHD incidence 29.2%.
- Clinical Relevance: CHI-AZA maintenance demonstrated durable remission and favorable tolerability post-alloHSCT, suggesting potential to reduce relapse risk in high-risk AML; further controlled, larger studies are warranted for validation.
Dual epigenetic maintenance therapy with chidamide and azacitidine (CHI-AZA) was effective and showed acceptable toxicity among patients with high-risk acute myeloid leukemia (AML) following allogeneic hematopoietic stem cell transplantation (alloHSCT), according to study results published in Clinical Epigenetics.
In efforts to minimize the incidence of chronic graft-versus-host disease (GVHD) and lower minimal residual disease, researchers conducted a phase 2 study evaluating the safety and efficacy of chidamide and azacitidine among patients with AML after alloHSCT.
The primary end point was cumulative incidence of relapse (CIR), and secondary end points were overall survival (OS) and relapse-free survival (RFS).
The prospective, open-label study (ChiCTR2300067593) enrolled 48 patients with high-risk AML between November 2021 and March 2024 were enrolled and treated. Patients received chidamide (5 mg orally, days 1 to 5) and azacitidine (75 mg/m² subcutaneously, days 1 to 5) in 28-day cycles starting ≥3 months after transplant. A total of 6 cycles were received by 54.2% of patients, while 83.3% received at least 3 cycles.
The median follow-up period was 26.9 months (range, 14.2 to 43.4). The 2-year CIR was 8.4% (95% confidence interval [CI], 4.4 to 12.4%), while 2-year relapse-free survival (RFS) was 91.6% (95% CI, 87.6 to 95.6%) and overall survival (OS) 97.9% (95% CI, 95.8 to 100%), respectively. Relapse occurred in 4 patients. The most common adverse events were hematologic, with no grade ≥ 4 events reported. Graft-versus-host disease (GVHD) occurred in 29.2% of patients.
The researchers concluded, “In conclusion, the results of our study suggested that dual epigenetic targeting maintenance treatment with CHI-AZA has an acceptable toxicity profile and might potentially be effective to prevent relapse after alloHSCT.”
They added, “Given the single-arm design of our study and the absence of a comparator arm, our findings warrant further prospective, controlled studies with larger sample sizes to validate furtherly.”
Source:
Wu YX, Wan CL, Tan KW, et al. Phase II study of dual epigenetic targeting with chidamide and azacitidine in patients with high-risk acute myeloid leukemia after allo-HSCT. Clinical Epigenetics. Published online October 13, 2025. doi:10.1186/s13148-025-01987-w
