Division of Hematology/Oncology, College of Physicians and Surgeons, Columbia University, New York, NY. United States.
Curr Cancer Drug Targets. 2017;17(9):846-857. doi: 10.2174/1568009617666170214104426.
Multiple myeloma (MM) is a hematological cancer caused by a proliferation of clonal plasma cells, leading to anemia, renal failure, hypercalcemia and destructive bone lesions resulting in significant morbidity. The overall survival has significantly improved with the incorporation of immunomodulatory drugs (IMiDs) and proteasome inhibitors (PI).
Here we provide a comprehensive review on IMiDs including molecular mechanisms, recent advances in therapeutic applications and management of toxicities in the treatment of MM.
Relevant publications in peer reviewed journals were retrieved by a selective search of PubMed. Systemic reviews, meta-analyses, randomized controlled trials, and treatment recommendations were reviewed and are summarized here.
Thalidomide, a first generation IMiD, is associated with significant toxicity in older patients. Lenalidomide, a more potent second generation IMiD with fewer side effects than thalidomide, is commonly used in newly-diagnosed multiple myeloma, relapsed refractory myeloma and as maintenance therapy after autologous stem cell transplantation (ASCT). Pomalidomide, a third generation IMiD, is 10 times more potent than lenalidomide and has shown impressive results in relapsed MM patients and in those refractory to both lenalidomide and bortezomib.
The clinical use of IMiDs in MM has significantly improved long-term survival and quality of life. Future studies are looking into novel biomarkers predictive of outcome in MM and new combinations of lenalidomide and pomalidomde with PI, monoclonal antibodies, immune checkpoint blockers and several other chemotherapies.
多发性骨髓瘤（MM）是一种由克隆性浆细胞增殖引起的血液系统恶性肿瘤，导致贫血、肾衰竭、高钙血症和破坏性骨病变，从而导致发病率显著增加。随着免疫调节剂（IMiD）和蛋白酶体抑制剂（PI）的应用，整体生存率得到了显著提高。
本文全面综述了 IMiD，包括其分子机制、治疗应用的最新进展以及在 MM 治疗中不良反应的管理。
通过选择性搜索 PubMed 检索了同行评议期刊上的相关出版物。综述了系统评价、荟萃分析、随机对照试验和治疗建议，并在此进行总结。
第一代 IMiD 沙利度胺在老年患者中具有显著毒性。来那度胺是一种更有效的第二代 IMiD，其副作用比沙利度胺少，常用于新诊断的多发性骨髓瘤、复发性难治性骨髓瘤以及自体干细胞移植（ASCT）后维持治疗。泊马度胺是一种第三代 IMiD，比来那度胺强 10 倍，在复发性 MM 患者和对来那度胺和硼替佐米均耐药的患者中显示出令人印象深刻的疗效。
IMiD 在 MM 中的临床应用显著提高了长期生存率和生活质量。未来的研究正在探索新的生物标志物，以预测 MM 的预后，并研究来那度胺和泊马度胺与 PI、单克隆抗体、免疫检查点抑制剂和其他几种化疗药物的新组合。
