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Drugs. 2013 Jul;73(11):1183-96. doi: 10.1007/s40265-013-0071-x.
Lenalidomide (Revlimid(®)), a thalidomide analogue, is an orally administered second generation immunomodulator with anti-angiogenic, antineoplastic, anti-inflammatory and pro-erythropoietic properties. It is approved for the treatment of patients with transfusion-dependent anaemia due to International Prognostic Scoring System low- or intermediate-1-risk myelodysplastic syndrome (MDS) associated with either chromosome 5q deletion [del(5q)] with or without additional cytogenetic abnormalities (US, Japan and Switzerland etc.), or with an isolated del(5q) cytogenetic abnormality when other therapeutic options are insufficient or inadequate (EU) [featured indication]. In a randomized, double-blind, multicentre, registrational trial (MDS-004; n = 205) in this patient population, a significantly higher proportion of lenalidomide recipients than placebo recipients achieved red blood cell transfusion independence for ≥26 consecutive weeks (primary endpoint for efficacy) and cytogenetic responses. The erythroid response to lenalidomide was accompanied by an increase in the haemoglobin levels. These efficacy outcomes are generally consistent with those seen in an earlier noncomparative registrational trial (MDS-003; n = 148). In MDS-004, lenalidomide also significantly improved health-related quality of life compared with placebo at 12 weeks. Retrospective analyses that compared outcomes between lenalidomide-treated patients with low- or intermediate-1-risk del(5q) MDS and multicentre registry cohorts showed that lenalidomide treatment did not appear to increase the risk of progression to acute myeloid leukaemia. Lenalidomide had a manageable safety profile in the registrational trials, with ≤20 % of patients discontinuing treatment because of adverse events. The most common adverse events (incidence ≥20 %) occurring in lenalidomide recipients were thrombocytopenia and neutropenia, which were generally managed by dosage reductions and/or interruptions, and/or pharmacotherapy. Thus, lenalidomide is a useful option for the treatment of patients with transfusion-dependent anaemia due to low- or intermediate-1-risk del(5q) MDS, with or without additional cytogenetic abnormalities.
来那度胺(雷利度胺),一种沙利度胺类似物,是一种口服的第二代免疫调节剂,具有抗血管生成、抗肿瘤、抗炎和促红细胞生成作用。它被批准用于治疗因国际预后评分系统低危或中危 1 级骨髓增生异常综合征(MDS)相关输血依赖型贫血的患者,这些患者存在染色体 5q 缺失[del(5q)],或伴有或不伴有其他细胞遗传学异常(美国、日本和瑞士等),或存在孤立的 del(5q)细胞遗传学异常,而其他治疗选择不足或不充分(欧盟)[主要适应证]。在该患者人群中进行的一项随机、双盲、多中心、注册试验(MDS-004;n=205)中,与安慰剂组相比,来那度胺组有更高比例的患者达到红细胞输注独立性≥26 周(疗效的主要终点)和细胞遗传学反应。来那度胺的红细胞反应伴随着血红蛋白水平的升高。这些疗效结果与早期非比较性注册试验(MDS-003;n=148)中的结果基本一致。在 MDS-004 中,与安慰剂相比,来那度胺在 12 周时还显著改善了健康相关生活质量。回顾性分析比较了低危或中危 1 级 del(5q) MDS 接受来那度胺治疗的患者与多中心登记队列的结局,结果表明来那度胺治疗似乎并未增加向急性髓性白血病进展的风险。在注册试验中,来那度胺具有可管理的安全性特征,仅有≤20%的患者因不良事件而停止治疗。在来那度胺组中最常见的不良事件(发生率≥20%)是血小板减少和中性粒细胞减少,这些不良事件通常通过降低剂量和/或中断用药以及/或药物治疗来处理。因此,来那度胺是治疗低危或中危 1 级 del(5q) MDS 相关输血依赖型贫血患者的一种有效选择,无论是否伴有其他细胞遗传学异常。