Immunomodulatory Drugs in Multiple Myeloma: Mechanisms of Action and Clinical Experience.
Immunomodulatory Drugs in Multiple Myeloma: Mechanisms of Action and Clinical Experience.
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DOI：
10.1007/s40265-017-0689-1
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发表时间：
2017-04
期刊：
影响因子：
11.5
通讯作者：
McCarthy PL
中科院分区：
文献类型：
--
作者：
Holstein SA;McCarthy PL
在过去的二十年里，多发性骨髓瘤（一种浆细胞恶性肿瘤）患者的预后有了显著改善。包括沙利度胺、来那度胺和泊马度胺在内的免疫调节药物（IMiD）的开发显著改善了这些结局。虽然沙利度胺现在不太常见，但来那度胺广泛用于治疗新诊断的符合移植条件和不符合移植条件的患者，用于移植后维持治疗和复发/难治性治疗，而泊马度胺目前用于复发/难治性治疗。IMiD已被报道具有多种活性，包括抗血管生成、细胞毒性和免疫调节，然而，最近发现IMiD与cereblon结合，从而调节关键转录因子（包括IKZF 1和IKZF 3）的泛素化，这为它们的作用机制提供了更深入的了解。在这里，这些药物在骨髓瘤的临床疗效进行审查，以及讨论的结构-功能关系，作用的分子机制，并与第二原发恶性肿瘤和血栓形成IMiDs的关联。
Over the last two decades, the outcomes for patients with multiple myeloma, a plasma cell malignancy, have dramatically improved. The development of the immunomodulatory drugs (IMiDs) which include thalidomide, lenalidomide, and pomalidomide, has contributed significantly to these improved outcomes. While thalidomide is now less commonly prescribed, lenalidomide is widely used in the treatment of newly diagnosed transplant-eligible and transplant-ineligible patients, in the maintenance setting post-transplant and in the relapsed/refractory setting, while pomalidomide is currently utilized in the relapsed/refractory setting. The IMiDs have been reported to have a multitude of activities, including anti-angiogenic, cytotoxic, and immunomodulatory, however, the more recent discoveries that the IMiDs bind to cereblon and thus regulate the ubiquitination of key transcription factors including IKZF1 and IKZF3, have provided greater insight into their mechanism of action. Here the clinical efficacy of these agents in myeloma is reviewed as well as discussion of structure-function relationship, the molecular mechanisms of action, and the association of IMiDs with second primary malignancies and thrombosis.
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