Hematology Department, Hospital Clínico San Carlos Universidad Complutense, Madrid, Spain.
Curr Med Res Opin. 2011 May;27(5):951-60. doi: 10.1185/03007995.2011.561834. Epub 2011 Mar 7.
Current guidelines support the use of erythropoiesis-stimulating agents for the treatment of anemia associated with low-risk myelodysplastic syndromes (MDS).
Single-arm, open-label, multi-center, phase 2 trial that evaluated the efficacy and safety of darbepoetin alfa (DA) in patients with low or intermediate-risk MDS, hemoglobin <100 g/L, erythropoietin (EPO) levels <500 IU/L and transfusion requirements <2 units/month over the preceding 2 months. Erythroid response (major [MaR] or minor [MiR]) and fatigue (Functional Assessment of Cancer Therapy-Fatigue [FACT-F]) were evaluated at 8, 16 and 24 weeks. DA was initiated at 300 μg weekly. For patients who did not achieve MaR by 8 weeks, filgrastim 300 μg weekly was added.
clinicaltrials.gov identifier: NCT01039350.
Forty-four patients (72.7% transfusion independent) were included. Median age was 76.0 years (range 41.3-92.4), 54.5% were male, and 90.9% presented ECOG Status (0-1). Eighteen patients received filgrastim. An erythroid response was achieved by 31 of 44 patients (70.5%) at week 8 (47.7% MaR, 22.7% MiR), 31 of 44 patients (70.5%) at week 16 (61.4% MaR, 9.1% MiR), and 32 of 44 patients (72.7%) at week 24 (61.3% MaR, 11.4% MiR). Mean (95% CI) change in FACT-F at week 24 was 3.61 (0.72 to 6.51). Baseline EPO levels <100 IU/L were a predictive factor of response. DA was well tolerated. Four mild (two iron deficiencies, flu syndrome and headache) and one fatal (thromboembolic event) adverse events were considered related to darbepoetin alfa.
A fixed dose of 300 μg of darbepoetin alfa weekly (with or without filgrastim) seems to be an effective and safe treatment for anemic patients with low or intermediate-risk MDS, low transfusion burden and EPO levels <500 IU/L. Results may not be extrapolable to unselected MDS patients.
目前的指南支持使用促红细胞生成素刺激剂治疗低危骨髓增生异常综合征（MDS）相关贫血。
这是一项单臂、开放标签、多中心、2 期临床试验，评估了达贝泊汀 α（DA）在血红蛋白<100 g/L、红细胞生成素（EPO）水平<500 IU/L 且前 2 个月每月输血需求<2 个单位的低危或中危 MDS 患者中的疗效和安全性。在第 8、16 和 24 周评估红细胞反应（主要[MaR]或次要[MiR]）和疲劳（癌症治疗功能评估-疲劳[FACT-F]）。DA 起始剂量为每周 300 μg。对于在 8 周时未达到 MaR 的患者，每周添加 300 μg 粒细胞集落刺激因子。
clinicaltrials.gov 标识符：NCT01039350。
44 例患者（72.7%无需输血）入选。中位年龄为 76.0 岁（范围 41.3-92.4），54.5%为男性，90.9%为 ECOG 状态（0-1）。18 例患者接受了粒细胞集落刺激因子治疗。44 例患者中有 31 例（70.5%）在第 8 周时达到红细胞反应（47.7%MaR，22.7%MiR），44 例患者中有 31 例（70.5%）在第 16 周时达到红细胞反应（61.4%MaR，9.1%MiR），44 例患者中有 32 例（72.7%）在第 24 周时达到红细胞反应（61.3%MaR，11.4%MiR）。第 24 周时 FACT-F 的平均（95%CI）变化为 3.61（0.72 至 6.51）。基线 EPO 水平<100 IU/L 是反应的预测因素。DA 耐受性良好。4 例轻微（2 例缺铁、流感综合征和头痛）和 1 例致命（血栓栓塞事件）不良事件被认为与达贝泊汀 α 相关。
每周 300 μg 固定剂量的达贝泊汀 α（加或不加粒细胞集落刺激因子）似乎是治疗低危或中危 MDS、低输血负担和 EPO 水平<500 IU/L 的贫血患者的有效且安全的治疗方法。结果可能不适用于未选择的 MDS 患者。
