Decitabine Plus Cedazuridine Maintenance Therapy Shows Promising Survival Outcomes for Acute Myeloid Leukemia and Myelodysplastic Syndromes
Key Clinical Summary
- Population and Design: Multicenter, phase 2, single-arm trial evaluated oral decitabine/cedazuridine (ASTX727) with optional donor lymphocyte infusion (DLI) as post–allogeneic HSCT maintenance therapy in 51 adults (median age 62 y) with very high-risk AML or MDS; 34 initiated ASTX727 beginning day 40 post-transplant for up to 10 cycles.
- Efficacy: Among the first 28 treated patients, 1-year disease-free survival (DFS) was 70.4% (95% CI, 55.1 to 89.9) at a 12.6-month median follow-up, demonstrating promising relapse prevention in this high-risk population.
- Safety: Grade ≥3 hematologic adverse events: neutropenia (62%), thrombocytopenia (24%), anemia (12%); serious adverse events in 41%, with 1 treatment-related death (thrombocytopenia).
- Clinical Relevance: ASTX727 ± DLI was well-tolerated and effective as a post-HSCT maintenance approach, suggesting a potential strategy to reduce relapse risk in very high-risk AML/MDS, warranting further validation in larger studies.
The combination of oral decitabine/cedazuridine (ASTX727) with optional donor lymphocyte infusion (DLI) demonstrated promising survival outcomes and manageable toxicity as post-transplant maintenance among patients with very high-risk acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS), according to results from the multicenter phase 2 GFM-DACORAL-DLI trial published in The Lancet Haematology.
Previous research suggests a reduction in relapse risk with a combination of a hypomethylating agent with donor lymphocyte infusion as maintenance therapy after hematopoietic stem-cell transplantation (HSCT) for acute myeloid leukemia and myelodysplastic syndrome. Researchers conducted a multicenter, single-arm study to determine the efficacy and safety of oral decitabine and cedazuridine (ASTX727).
Patients aged 18 to 70 with poor- or very poor-risk MDS or adverse-risk AML, including those with unfavorable genetics, therapy-related disease, or early relapse after prior remission. ASTX727 was initiated on day 40 post–allogeneic HSCT and administered orally in escalating doses (1 to 3 days per 28-day cycle) for up to 10 cycles. Donor lymphocyte infusion was recommended beginning after cycle 4 in eligible patients. The primary end point was 1-year disease-free survival (DFS) in the first 28 patients who received ASTX727, safety was evaluated in all treated patients.
Overall, 51 patients underwent allogeneic HSCT and 34 initiated ASTX727 maintenance therapy. The median age of all patients was 62 years (interquartile range [IQR], 56.5 to 65.0). At a median follow-up of 12.6 months, the 1-year DFS among the first 28 treated patients was 70.4% (95% confidence interval [CI], 55.1 to 89.9).
In terms of safety, hematologic adverse events included grade ≥ 3 neutropenia (62%), thrombocytopenia (24%), and anemia (12%). Serious adverse events occurred among 41% of treated patients, and 1 treatment-related death due to thrombocytopenia was reported.
The researchers concluded, “ASTX727 could be a potential treatment option after HSCT in patients with acute myeloid leukemia or myelodysplastic syndrome at very high risk of relapse.”
They added, “Further investigation is warranted to establish the efficacy and safety of this therapeutic approach.”
Source:
Robin M, D’Aveni M, Stamatoullas A, et al. Oral decitabine and cedazuridine maintenance after haematopoietic stem-cell transplantation in very high-risk acute myeloid leukaemia or myelodysplastic syndrome (GFM-DACORAL-DLI): a multicentre, single-arm, phase 2 trial. The Lancet Haematology. Published online August 7, 2025. doi:10.1016/S2352-3026(25)00172-3
