RT Journal Article
T1 Phase III, Randomized, Placebo-Controlled Trial of CC-486 (Oral Azacitidine) in Patients With Lower-Risk Myelodysplastic Syndromes.
A1 Garcia-Manero, Guillermo
A1 Santini, Valeria
A1 Almeida, Antonio
A1 Platzbecker, Uwe
A1 Jonasova, Anna
A1 Silverman, Lewis R
A1 Falantes, Jose
A1 Reda, Gianluigi
A1 Buccisano, Francesco
A1 Fenaux, Pierre
A1 Buckstein, Rena
A1 Diez Campelo, Maria
A1 Larsen, Stephen
A1 Valcarcel, David
A1 Vyas, Paresh
A1 Giai, Valentina
A1 Olíva, Esther Natalie
A1 Shortt, Jake
A1 Niederwieser, Dietger
A1 Mittelman, Moshe
A1 Fianchi, Luana
A1 La Torre, Ignazia
A1 Zhong, Jianhua
A1 Laille, Eric
A1 Lopes de Menezes, Daniel
A1 Skikne, Barry
A1 Beach, C L
A1 Giagounidis, Aristoteles
AB Treatment options are limited for patients with lower-risk myelodysplastic syndromes (LR-MDS). This phase III, placebo-controlled trial evaluated CC-486 (oral azacitidine), a hypomethylating agent, in patients with International Prognostic Scoring System LR-MDS and RBC transfusion-dependent anemia and thrombocytopenia. Patients were randomly assigned 1:1 to CC-486 300-mg or placebo for 21 days/28-day cycle. The primary end point was RBC transfusion independence (TI). Two hundred sixteen patients received CC-486 (n = 107) or placebo (n = 109). The median age was 74 years, median platelet count was 25 × 109/L, and absolute neutrophil count was 1.3 × 109/L. In the CC-486 and placebo arms, 31% and 11% of patients, respectively, achieved RBC-TI (P = .0002), with median durations of 11.1 and 5.0 months. 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, and more CC-486 patients had ≥ 1.5 g/dL hemoglobin increases from baseline (23.4% v 4.6%). Platelet hematologic improvement rate was higher with CC-486 (24.3% v 6.5%). Underpowered interim overall survival analysis showed no difference between CC-486 and placebo (median, 17.3 v 16.2 months; P = .96). Low-grade GI events were the most common adverse events in both arms. In the CC-486 and placebo arms, 90% and 73% of patients experienced a grade 3-4 adverse event. Overall death rate was similar between arms, but there was an imbalance in deaths during the first 56 days (CC-486, n = 16; placebo, n = 6), most related to infections; the median pretreatment absolute neutrophil count for the 16 CC-486 patients was 0.57 × 109/L. CC-486 significantly improved RBC-TI rate and induced durable bilineage improvements in patients with LR-MDS and high-risk disease features. More early deaths occurred in the CC-486 arm, most related to infections in patients with significant pretreatment neutropenia. Further evaluation of CC-486 in MDS is needed.
YR 2021
FD 2021-03-25
LK http://hdl.handle.net/10668/17400
UL http://hdl.handle.net/10668/17400
LA en
DS RISalud
RD Jul 30, 2025