Department of Hematology, Seoul St. Mary's Hematology Hospital, College of Medicine, Catholic University of Korea, Seoul, Korea.
Leukemia Research Institute, College of Medicine, Catholic University of Korea, Seoul, Korea.
Cancer. 2022 Dec 1;128(23):4095-4108. doi: 10.1002/cncr.34492. Epub 2022 Oct 8.
Low-dose azacitidine (AZA) regimens, primarily 5-day AZA, have been used in lower risk myelodysplastic syndrome (LrMDS) but they have yet to be directly compared to the standard 7-day, uninterrupted dosing schedule.
In this phase 2, multicenter, randomized trial, 55 patients with adult LrMDS (low and intermediate-1 risk by international prognostic scoring system [IPSS]) were randomly assigned and received either 5-day (n = 26) or 7-day (n = 29) AZA between March 2012 and August 2020. The trial was stopped prematurely because of the slow accrual of patients. The primary end point was the overall response rate (ORR) of the 5-day AZA as compared to that of the 7-day regimen.
Median patient age was 59 years, and IPSS intermediate-1 risk comprised the majority (81.8%). The median number of cycles in both arms was six. In the ITT subset (n = 53), in each of the 5-day and 7-day arms, the ORR of 48.0% and 39.3%, hematologic improvement of 44.0% and 39.3%, and RBC transfusion independence of 35.3% and 40.0% were observed respectively, and none of these findings were significantly different between the two arms. A cytogenetic response rate was significantly higher in the 7-day arm (8.3% and 53.8%, p = .027). Survival and adverse events were similar between the groups, although gastrointestinal toxicities, grade ≥3 thrombocytopenia, and febrile neutropenia were less frequent in the 5-day arm.
The 5-day AZA in LrMDS showed comparable efficacy to a 7-day regimen in terms of similar overall response and other outcomes, despite significantly higher rates of cytogenetic responses in the 7-day regimen.
Azacitidine (75 mg/m /day for 7 consecutive days per 28-day cycle) has shown survival benefit in patients with higher risk myelodysplastic syndrome (MDS). Although the use of azacitidine is less-well studied for lower risk MDS, it is generally accepted as a feasible option for lower risk MDS (LrMDS).
低剂量阿扎胞苷（AZA）方案，主要是 5 天 AZA，已用于低危骨髓增生异常综合征（LrMDS），但尚未与标准的 7 天、不间断给药方案进行直接比较。
在这项 2 期、多中心、随机试验中，55 名成年 LrMDS（国际预后评分系统[IPSS]低和中-1 风险）患者被随机分配并接受 5 天（n=26）或 7 天（n=29）AZA 治疗，时间为 2012 年 3 月至 2020 年 8 月。由于患者入组缓慢，试验提前停止。主要终点是 5 天 AZA 的总缓解率（ORR）与 7 天方案的比较。
中位患者年龄为 59 岁，大多数为 IPSS 中-1 风险（81.8%）。两组的中位治疗周期数均为 6 个。在意向性治疗（ITT）亚组（n=53）中，5 天和 7 天组的 ORR 分别为 48.0%和 39.3%，血液学改善率分别为 44.0%和 39.3%，红细胞输血独立性分别为 35.3%和 40.0%，这些发现均无显著差异。7 天组的细胞遗传学缓解率明显较高（8.3%和 53.8%，p=0.027）。两组的生存和不良事件相似，尽管 5 天组胃肠道毒性、≥3 级血小板减少和发热性中性粒细胞减少的发生率较低。
在 LrMDS 中，5 天 AZA 的疗效与 7 天方案相当，在总体反应和其他结局方面相似，尽管 7 天方案的细胞遗传学反应率明显较高。
阿扎胞苷（75mg/m /天，每 28 天周期连用 7 天）已显示出对高危骨髓增生异常综合征（MDS）患者的生存获益。尽管低危 MDS 中使用阿扎胞苷的研究较少，但它通常被认为是低危 MDS 的可行选择。
