Efficacy of lenalidomide in myelodysplastic syndromes
Efficacy of lenalidomide in myelodysplastic syndromes
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DOI：
10.1056/nejmoa041668
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发表时间：
2005-02-10
影响因子：
158.5
通讯作者：
Zeldis, JB
中科院分区：
文献类型：
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作者：
List, A;Kurtin, S;Zeldis, JB
背景：无效的红细胞生成是骨髓增生异常综合征的标志。由无效的红细胞生成引起的贫血的管理是困难的。在骨髓增生异常综合征和症状性贫血患者中，我们评估了来那度胺的安全性和血液学活性，来那度胺是一种新型的沙利度胺类似物。方法：43例输血依赖性或症状性贫血患者接受来那度胺治疗，剂量分别为25或10mg /天或10mg /天，每28天循环21天。所有患者要么对重组促红细胞生成素没有反应，要么内源性促红细胞生成素水平较高，从这种治疗中获益的可能性很低。16周后评估对治疗的反应。结果：中性粒细胞减少症和血小板减少症是最常见的不良事件，发生率分别为65%和74%，25例患者（58%）需要中断治疗或减少剂量。其他不良事件轻微且罕见。24名患者有反应（56%）：20名患者维持了输血独立性，1名患者血红蛋白水平每分升增加超过2克，3名患者输血需求减少了50%以上。在涉及5q31.1染色体的克隆间质缺失患者中，反应率最高（83%，而在核型正常患者中为57%，在其他核型异常患者中为12%；P=0.007）和预后风险较低的患者中，反应率最高。在20例核型异常患者中，11例在中期异常细胞减少了至少50%，其中10例（50%）细胞遗传学完全缓解。中位随访81周后，输血不依赖的中位持续时间尚未达到，中位血红蛋白水平为13.2 g /分升（范围为11.5至15.8）。结论：来那度胺对于对促红细胞生成素无反应或不太可能从常规治疗中获益的低风险骨髓增生异常综合征患者具有血液学活性。
BACKGROUND:Ineffective erythropoiesis is the hallmark of myelodysplastic syndromes. Management of the anemia caused by ineffective erythropoiesis is difficult. In patients with myelodysplastic syndromes and symptomatic anemia, we evaluated the safety and hematologic activity of lenalidomide, a novel analogue of thalidomide.METHODS:Forty-three patients with transfusion-dependent or symptomatic anemia received lenalidomide at doses of 25 or 10 mg per day or of 10 mg per day for 21 days of every 28-day cycle. All patients either had had no response to recombinant erythropoietin or had a high endogenous erythropoietin level with a low probability of benefit from such therapy. The response to treatment was assessed after 16 weeks.RESULTS:Neutropenia and thrombocytopenia, the most common adverse events, with respective frequencies of 65 percent and 74 percent, necessitated the interruption of treatment or a dose reduction in 25 patients (58 percent). Other adverse events were mild and infrequent. Twenty-four patients had a response (56 percent): 20 had sustained independence from transfusion, 1 had an increase in the hemoglobin level of more than 2 g per deciliter, and 3 had more than a 50 percent reduction in the need for transfusions. The response rate was highest among patients with a clonal interstitial deletion involving chromosome 5q31.1 (83 percent, as compared with 57 percent among those with a normal karyotype and 12 percent among those with other karyotypic abnormalities; P=0.007) and patients with lower prognostic risk. Of 20 patients with karyotypic abnormalities, 11 had at least a 50 percent reduction in abnormal cells in metaphase, including 10 (50 percent) with a complete cytogenetic remission. After a median follow-up of 81 weeks, the median duration of transfusion independence had not been reached and the median hemoglobin level was 13.2 g per deciliter (range, 11.5 to 15.8).CONCLUSIONS:Lenalidomide has hematologic activity in patients with low-risk myelodysplastic syndromes who have no response to erythropoietin or who are unlikely to benefit from conventional therapy.