两个表观遗传学药物联合使用:血液肿瘤“新玩法”

Blood

2017-08-03Article

13.164

影响因子

原标题:低剂量地西他滨和阿扎胞苷治疗MDS和MDS/MPN的随机二阶段研究

① 低甲基化药物(HMAs)可以提高高风险骨髓增生异常综合征(MDS)患者的生存率,现为研究低剂量地西他滨和阿扎胞苷对低风险MDS患者的安全性和有效性设计此试验;② 试验纳入113名在2012年11月到2016年2月间接受治疗的,中低风险MDS或MDS/骨髓增生性肿瘤(MPN)患者;③ 平均经过9个周期的治疗后,服用地西他滨和阿扎胞苷组的总体缓解率分别为70%和49%,细胞遗传学缓解率分别为61%和25%,6周死亡率为0;④ HMAs治疗低风险MDS或MDS/MPN是安全有效的。

骨髓增生异常综合征(MDS) 低风险疾病 低甲基化药物

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Title:
A randomized phase II study of low-dose decitabine versus low-dose azacitidine in lower risk MDS and MDS/MPN

DOI:
10.1182/blood-2017-06-788497

Abstract & Authors展开

Abstract:
Hypomethylating agents (HMAs) improve survival in patients with higher-risk myelodysplastic syndromes (MDS) but are less well-studied in lower-risk disease. We compared the safety and efficacy of low-dose decitabine versus low-dose azacitidine in this group of patients. Adults with low- or intermediate-1-risk MDS or MDS/myeloproliferative neoplasm (MPN), including chronic myelomonocytic leukemia, by the International Prognostic Scoring System were randomized using a Bayesian adaptive design to receive either azacitidine 75 mg/m(2) IV/SC daily or decitabine 20 mg/m(2) IV daily for 3 consecutive days on a 28-day cycle. The primary outcome was overall response rate (ORR). Between 11/2012 and 2/2016, 113 patients were treated, 40 (35%) with azacitidine and 73 (65%) with decitabine. The median age was 70 years; 81% of patients were intermediate-1-risk. The median number of cycles received was 9. The overall response rate was 70% and 49% (p=0.03) for patients treated with decitabine and azacitidine, respectively. Thirty-two percent of patients treated with decitabine became transfusion independent compared with 16% of patients treated with azacitidine (p=0.2). Cytogenetic response rates were 61% and 25% (p=0.02), respectively. With a median follow-up of 20 months, the overall median event-free survival was 18 months -- 20 and 13 months for patients treated with decitabine and azacitidine, respectively (p=0.1). Treatment was well tolerated with a 6-week mortality rate of 0%. The use of low-dose HMAs is safe and effective in patients with lower-risk MDS and MDS/MPN. Their impact on the natural history of lower-risk disease needs to be further studied. This trial was registered at clinicaltrials.gov (identifier NCT01720225).

All Authors:
Elias Jabbour,Nicholas J Short,Guillermo Montalban-Bravo,Xuelin Huang,Carlos Bueso-Ramos,Wei Qiao,Hui Yang,Chong Zhao,Tapan Kadia,Gautam Borthakur,Naveen Pemmaraju,Koji Sasaki,Zeev Estrov,Jorge Cortes,Farhad Ravandi,Yesid Alvarado,Rami Komrokji,Mikkael A Sekeres,David P Steensma,Amy DeZern,Gail Roboz,Hagop Kantarjian,Guillermo Garcia-Manero

First Authors:
Elias Jabbour

Correspondence:
Elias Jabbour

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