Hayden Patrick J, Mitsiades Constantine S, Anderson Kenneth C, Richardson Paul G
Dana Farber Cancer Institute, Boston, Massachusetts 02115, USA.
Curr Opin Hematol. 2007 Nov;14(6):609-15. doi: 10.1097/MOH.0b013e3282f0e948.
Several novel therapies have been licensed for the treatment of myeloma in recent years. We summarize some of the trials leading to their approval and the current evidence for their clinical use. A number of promising agents undergoing phase I/II trial evaluation are also discussed.
The immunomodulatory drugs, thalidomide and lenalidomide, and the proteasome inhibitor, bortezomib, have been shown to be effective agents, both alone and as part of combination regimens, for the treatment of myeloma. Studies are now focusing on the optimal sequencing of these drugs throughout the disease course, with a view to maximizing antitumor efficacy and minimizing overlapping toxicities. New protocols are increasingly based on preclinical evidence of synergy. The incorporation of these agents into transplant-based treatment protocols has improved outcomes. Other examples of novel agents undergoing assessment at present include arsenic trioxide, hsp90 inhibitors and histone deacetylase inhibitors. Future developments are likely to include individualized treatment plans based on patient-specific parameters including cytogenetic analysis and gene expression profiling.
Thalidomide, lenalidomide and bortezomib can now be considered as standard options both as first-line agents and beyond for the treatment of myeloma, with respective combinations also emerging as valid choices for all stages of the disease.
近年来，几种新型疗法已获许可用于治疗骨髓瘤。我们总结了一些促使它们获批的试验以及目前其临床应用的证据。还讨论了一些正在进行Ⅰ/Ⅱ期试验评估的有前景的药物。
免疫调节药物沙利度胺和来那度胺，以及蛋白酶体抑制剂硼替佐米，已被证明无论是单独使用还是作为联合治疗方案的一部分，都是治疗骨髓瘤的有效药物。目前的研究重点是在整个疾病过程中这些药物的最佳用药顺序，以实现抗肿瘤疗效最大化和重叠毒性最小化。新方案越来越多地基于协同作用的临床前证据。将这些药物纳入基于移植的治疗方案已改善了治疗结果。目前正在评估的新型药物的其他例子包括三氧化二砷、热休克蛋白90抑制剂和组蛋白去乙酰化酶抑制剂。未来的发展可能包括基于患者特定参数（包括细胞遗传学分析和基因表达谱）的个体化治疗方案。
沙利度胺、来那度胺和硼替佐米现在可被视为治疗骨髓瘤的一线及后续治疗的标准选择，各自的联合用药方案也已成为该病各个阶段的有效选择。
