MDS-308 Impact of Two Azacitidine Administration Schedules in Myelodysplastic Syndromes

Abstract

Myelodysplastic syndromes are a rare group of diseases that manifest as progressive cytopenias and carry a risk of progression to acute myeloid leukemia. Apart from transplantation, only azacitidine demonstrated a survival benefit in a randomized phase 3 study in higher-risk patients. The approved azacitidine regimen is 75 mg/m2/day for 7 consecutive days, imposing a logistic challenge for outpatient weekend administration. Schedules of 5 days and 7 days with a weekend break (5+2) have been studied. However, the quality of the evidence is low; most studies were performed in low-risk populations and with total dose reduction in 5-day schedules. We performed a single-center, retrospective cohort study to compare the outcomes of full-dose azacitidine (7×75 mg/m2) administered in 5-day and 5+2-day schedules in a higher-risk cohort. We evaluated 100 patients for overall survival (primary outcome) and a subsample of 49 patients for secondary outcomes, including acute myeloid leukemia-free survival, probability of infections, and transfusion burden. Kaplan-Meier analysis and Cox proportional hazards models were used for survival analyses. Linear and logistic regressions were applied for univariate and multivariate prediction, as appropriate. After a median follow-up of 10.8 months, patients treated with a 5-day schedule had a median overall survival of 12.5 months versus 15.0 months in the 5+2 group: log-rank P=0.97; HR 0.95 (95% CI 0.57-1.56). Acute myeloid leukemia-free survival was also similar between groups: log-rank P=0.22; HR 1.70 (95% CI 0.70-4.14). Azacitidine schedules were not predictive of infections or the number of red blood cell or platelet transfusions in multivariate analysis. Full-dose azacitidine (7×75 mg/m2) can be administered both in 5 days and 7 days with a weekend break with no significant difference in survival, infection, or transfusional outcomes.