Five-day versus 7-day treatment regimen with azacitidine in lower risk myelodysplastic syndrome: A phase 2, multicenter, randomized trial

Background Low-dose azacitidine (AZA) regimens, primarily 5-day AZA, have been used in lower risk myelodysplastic syndrome (LrMDS) but they have yet to be directly compared to the standard 7-day, uninterrupted dosing schedule. Method In this phase 2, multicenter, randomized trial, 55 patients with adult LrMDS (low and intermediate-1 risk by international prognostic scoring system [IPSS]) were randomly assigned and received either 5-day (n = 26) or 7-day (n = 29) AZA between March 2012 and August 2020. The trial was stopped prematurely because of the slow accrual of patients. The primary end point was the overall response rate (ORR) of the 5-day AZA as compared to that of the 7-day regimen. Results Median patient age was 59 years, and IPSS intermediate-1 risk comprised the majority (81.8%). The median number of cycles in both arms was six. In the ITT subset (n = 53), in each of the 5-day and 7-day arms, the ORR of 48.0% and 39.3%, hematologic improvement of 44.0% and 39.3%, and RBC transfusion independence of 35.3% and 40.0% were observed respectively, and none of these findings were significantly different between the two arms. A cytogenetic response rate was significantly higher in the 7-day arm (8.3% and 53.8%, p = .027). Survival and adverse events were similar between the groups, although gastrointestinal toxicities, grade >= 3 thrombocytopenia, and febrile neutropenia were less frequent in the 5-day arm. Conclusion The 5-day AZA in LrMDS showed comparable efficacy to a 7-day regimen in terms of similar overall response and other outcomes, despite significantly higher rates of cytogenetic responses in the 7-day regimen. Lay summary Azacitidine (75 mg/m(2)/day for 7 consecutive days per 28-day cycle) has shown survival benefit in patients with higher risk myelodysplastic syndrome (MDS). Although the use of azacitidine is less-well studied for lower risk MDS, it is generally accepted as a feasible option for lower risk MDS (LrMDS).