Decitabine plus all-trans retinoic acid versus decitabine monotherapy for myelodysplastic syndromes with excess blasts: a multicenter, randomized controlled trial

Abstract

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 (MDS-EB) 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 4 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 [OR] 3.40; 95% confidence interval [CI] 1.90–6.09; p<0.001). The ATRA group also had a higher complete remission rate (23% versus 12%; OR 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 (OS) 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 ChiCTR1800018307