Zangari Maurizio, Elice Francesca, Tricot Guido
Myeloma Institute for Research and Therapy, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA.
Expert Opin Investig Drugs. 2005 Nov;14(11):1411-8. doi: 10.1517/13543784.14.11.1411.
Immunomodulatory drugs (IMiDs) are thalidomide analogues that retain the direct anticancer cytotoxic and immunological activity of their parent compound, but with a different toxicity profile. In vitro studies show that IMiDs have a more potent antitumour effect than thalidomide on multiple myeloma (MM) cell lines. This activity is mediated by multiple mechanisms: direct antiproliferative effect; inhibition of angiogenesis due to reduced IL-6 and vascular endothelial growth factor secretion; inhibition of cytokines production, especially TNF-alpha; and stimulation of T-cell activity. Two IMiDs, CC-5013 and CC-4047, have been tested in clinical trials in MM patients with progressive or refractory disease, and one trial is ongoing in newly diagnosed MM patients. Observed toxicities include thrombocytopoenia, neutropoenia and cardiovascular events, but no significant neurotoxicity has been reported. Partial responses (> or = 50% reduction in M-protein) ranged from 20 to 71% in different studies depending on the pretreatment status of the patients. The combination of IMiDs with dexamethasone may be beneficial.
免疫调节药物（IMiDs）是沙利度胺类似物，保留了其母体化合物直接的抗癌细胞毒性和免疫活性，但毒性特征有所不同。体外研究表明，IMiDs对多发性骨髓瘤（MM）细胞系的抗肿瘤作用比沙利度胺更强。这种活性由多种机制介导：直接抗增殖作用；由于白细胞介素-6和血管内皮生长因子分泌减少而抑制血管生成；抑制细胞因子产生，尤其是肿瘤坏死因子-α；以及刺激T细胞活性。两种IMiDs，CC-5013和CC-4047，已在进展性或难治性疾病的MM患者中进行临床试验测试，一项针对新诊断MM患者的试验正在进行中。观察到的毒性包括血小板减少、中性粒细胞减少和心血管事件，但未报告明显的神经毒性。根据患者的预处理状态，不同研究中的部分缓解（M蛋白降低≥50%）率在20%至71%之间。IMiDs与地塞米松联合使用可能有益。
