Garcia-Manero G, Santini V, Almeida A, et al. - Researchers tested CC-486 (oral azacitidine), a hypomethylating agent, among patients suffering from International Prognostic Scoring System lower-risk myelodysplastic syndromes (LR-MDS) and RBC transfusion–dependent anemia and thrombocytopenia in this phase 3, placebo-controlled trial. They randomized 216 patients at a 1:1 ratio to CC-486 300-mg or placebo for 21 days/28-day cycle. RBC transfusion independence (TI) was considered as the primary endpoint. Among patients suffering from LR-MDS and exhibiting high-risk disease characteristics, a significant improvement in RBC-TI rate as well as durable bilineage improvements were shown to be conferred by CC-486 in this study. In the CC-486 arm, 31% of patients achieved RBC-TI with median duration of 11.1 months, while in the and placebo arm, 11% of patients achieved RBC-TI with a median duration of 5.0 months. In the CC-486 and placebo arms, reductions of ≥ 4 RBC units were attained by 42.1% and 30.6% of patients, respectively, with median durations of 10.0 and 2.3 months; more CC-486 patients had ≥ 1.5 g/dL hemoglobin increases from baseline (23.4%) vs placebo (4.6%) and platelet hematologic improvement rate was higher with CC-486 (24.3% vs 6.5%). In the CC-486 arm, occurrence of more early deaths was noted, most associated with infections in cases with significant pretreatment neutropenia.