Decitabine plus all-trans retinoic acid versus decitabine monotherapy for myelodysplastic syndromes with excess blasts: a multicenter, randomized controlled trial.
- 2025-11-20
- Haematologica 111(5)
- Xinping Zhou
- Yanjuan Lin
- Yan Gao
- Zheng Ge
- Li Huang
- Jin Zhang
- Hai Cheng
- Guifang Ouyang
- Fanjun Meng
- Yulu Tian
- Yuemin Kuang
- Fengping Zhou
- Lixia Sheng
- Weimei Jin
- Gaixiang Xu
- Liya Ma
- Li Ye
- Chen Mei
- Jian Li
- Jie Jin
- Hongyan Tong
- PubMed: 41262042
- DOI: 10.3324/haematol.2025.288526
Study Design
- Type
- Randomized Controlled Trial (RCT)
- Sample size
- n = 227
- Population
- untreated patients with MDS with excess blasts (MDSEB)
- Methods
- multicenter controlled trial randomized (1:1) to ATRA plus decitabine (ATRA at 25 mg/m2/day in 2 divided daily doses throughout the 28-day cycle plus decitabine at 20 mg/m2 on days 1-5) or decitabine alone (20 mg/m2 on days 1-5)
- Blinding
- Open-label
- Duration
- four treatment cycles (28-day cycle)
- Funding
- Unclear
- Large Human Trial
Despite standard treatment with hypomethylating agents, the prognosis of patients with higher-risk myelodysplastic syndrome (MDS) remains poor. All-trans retinoic acid (ATRA) has demonstrated promising efficacy in unfit patients with acute myeloid leukemia. This multicenter controlled trial randomized (1:1) untreated patients with MDS with excess blasts (MDSEB) to ATRA plus decitabine (ATRA at 25 mg/m2/day in 2 divided daily doses throughout the 28-day cycle plus decitabine at 20 mg/m2 on days 1-5) or decitabine alone (20 mg/m2 on days 1-5). The primary endpoint was the overall response rate within four treatment cycles. A total of 227 patients were randomized. Four patients who did not commence therapy were excluded from the modified intention-to-treat (mITT) analysis. The median patient age was 62 years (range, 19-81). The overall response rate was 78% (86/110) in the ATRA group versus 51% (58/113) in the decitabine group (odds ratio =3.40; 95% confidence interval P<0.001). The ATRA group also had a higher complete remission rate (23% vs. 12%; odds ratio =2.05; 95% CI: 1.02-4.25; P=0.042). With a median follow-up of 30.1 months, progression-free survival (PFS) was 14.9 months in the ATRA group versus 10.5 months in the decitabine group (hazard ratio [HR]=0.70; 95% CI: 0.51-0.97; P=0.03). The overall survival was 23.0 months and 19.3 months, respectively (HR=0.77; 95% CI: 0.54-1.09; P=0.137). The two groups did not differ in grade 3 or higher hematological adverse events. In conclusion, adding ATRA to decitabine increased the overall response rate and prolonged PFS in adult patients with MDS-EB without increasing hematological toxicity. This study was registered at Chinese Clinical Trial Registry (www.chictr.org.cn, identifier: ChiCTR1800018307).