Full-Dose Azacitidine in 5 Days Versus 7 Days with a Weekend Break in Myelodysplastic Syndromes: A Retrospective Cohort Study.

Azacitidine 75 mg/m2 /day for 7 days is a standard-of-care for patients with MDS. However, weekend outpatient administration is challenging. Five days and 7 days with a weekend break (5 + 2) have been used despite absence of strong evidence. We evaluated the impact of full-dose azacitidine (7 x 75 mg/m2) in 5 or 5 + 2 days: there was no difference in survival, infection or transfusional outcomes. Introduction: Apart from transplantation, only azacitidine demonstrated a survival benefit in a phase III study in higherrisk myelodysplastic syndromes (MDS). The approved regimen is 75 mg/m2 /day for 7 consecutive days, imposing a logistic challenge for outpatient weekend administration. Schedules with 5 days and 7 days with a weekend break (5 + 2) have been used for convenience despite the lack of strong scientific support. Most studies of alternative schedules were performed in lower-risk MDS and with dose reduction in the 5-day schedules. Methods: We performed a single-center, retrospective cohort study to compare full-dose azacitidine (7 x 75 mg/m2) administration in 5-day and 5 + 2-day schedules in a higher-risk MDS cohort. We evaluated 100 patients for overall survival and a subsample (49 patients) for acute myeloid leukemia-free survival (AMLFS), probability of infections and transfusion burden. Kaplan-Meier analysis and Cox models were used for survival analyses. Linear and logistic regressions were applied for univariate and multivariate assessment. Results: 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: HR 0.95 (95% CI, 0.57-1.56); P= .83. AMLFS was also similar between groups: HR 1.70 (95% CI, 0.70-4.14); P = .24. Azacitidine schedules were not predictive of infections nor number of red blood cell or platelet transfusions in multivariate analyses. Conclusions: In higher-risk MDS, full-dose azacitidine (7 x 75 mg/m2) can be administered both in 5 days and in 7 days with a weekend break with no significant difference in survival, infection or transfusional outcomes.