H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA.
Semin Oncol. 2011 Oct;38(5):648-57. doi: 10.1053/j.seminoncol.2011.04.015.
Lenalidomide is characterized as an immunomodulatory drug (IMiD), a second-generation drug in this proprietary drug class with greater potency and a toxicity profile that is distinct from the lead compound, thalidomide. Clinical trials exploring its role in treating patients with myelodysplastic syndrome (MDS) revealed unique karyotype-specific activity in patients with interstitial deletion of the long arm of chromosome 5 (del(5q)). This observation ultimately led the US Food and Drug Administration (FDA) to approve lenalidomide for the treatment of lower risk transfusion-dependent patients with del(5q) MDS. Herein we review the results of four clinical trials conducted with lenalidomide in lower risk MDS, summarizing the clinical efficacy and safety of the drug. We discuss the use of lenalidomide in non-del(5q) patients and efforts to optimize its activity, in addition to investigations exploring the role of lenalidomide in higher risk MDS and acute myeloid leukemia (AML). Finally, we highlight the current understanding of its mechanism of action, discussing the emerging insight into the underlying biology of del(5q) MDS and its linkage to potential targets of lenalidomide.
来那度胺被归类为一种免疫调节药物（IMiD），是该专利药物类别中的第二代药物，其效力更强，毒性特征与先导化合物沙利度胺不同。探索其在治疗骨髓增生异常综合征（MDS）患者中的作用的临床试验表明，在具有染色体 5 长臂间缺失（del(5q)）的患者中具有独特的核型特异性活性。这一观察结果最终促使美国食品和药物管理局（FDA）批准来那度胺用于治疗低风险输血依赖性 del(5q) MDS 患者。本文回顾了四项在低风险 MDS 中进行的来那度胺临床试验的结果，总结了该药的临床疗效和安全性。我们讨论了来那度胺在非 del(5q)患者中的应用以及优化其活性的努力，此外还探讨了来那度胺在高危 MDS 和急性髓细胞白血病（AML）中的作用。最后，我们强调了目前对其作用机制的理解，讨论了深入了解 del(5q) MDS 的潜在生物学及其与来那度胺潜在靶点的联系。
