The introduction of thalidomide, lenalidomide, and bortezomib has changed the way that multiple myeloma (MM) is treated and has greatly improved survival outcomes. These novel agents are often used in combination with conventional drugs, such as dexamethasone, to optimize clinical responses; however, they are also being evaluated as part of novel treatment combinations to build upon the success of available treatment regimens. Lenalidomide-based combinations are a focus of clinical research due to the high efficacy, good tolerability, and lack of cumulative toxicity associated with lenalidomide. Lenalidomide is an IMiDs® immunomodulatory compound with a dual mechanism of action - tumoricidal effects rapidly reduce MM burden while long-term immunomodulatory actions maintain tumor suppression. Several new agents with antimyeloma effects have been identified including: epigenetic agents (e.g. histone deacetylase inhibitors); novel proteasome inhibitors; novel immunomodulatory compounds; cyclin-dependent kinase inhibitors; interleukin-6 inhibitors; and other experimental agents such as heat-shock protein 90 inhibitors and monoclonal antibodies targeting MM cell surface receptors (e.g. anti-CS1 and anti-CD40). Many of these new agents, in combination with lenalidomide, are in early phases of clinical evaluation. Early clinical results are promising, indicating that the novel lenalidomide-based drug combinations are effective and generally well tolerated in patients with MM; future research will continue to evaluate these novel combinations and help to identify the optimal setting (e.g. induction, salvage, or maintenance) in which they may provide the greatest impact on the disease course.

中文翻译：

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多发性骨髓瘤的未来药物开发：基于来那度胺的新型联合疗法概述。

沙利度胺，来那度胺和硼替佐米的引入改变了多发性骨髓瘤（MM）的治疗方式，并大大改善了生存结果。这些新型药物通常与地塞米松等常规药物联合使用，以优化临床反应。但是，它们也正在作为新型治疗组合的一部分进行评估，以建立在可用治疗方案成功的基础上。基于来那度胺的组合由于其疗效高，耐受性好，缺乏来那度胺相关的累积毒性而成为临床研究的重点。来那度胺是一种具有双重作用机制的IMiDs®免疫调节化合物-杀肿瘤作用可迅速减少MM负担，而长期的免疫调节作用则可维持肿瘤抑制。已经发现了几种具有抗骨髓瘤作用的新药，包括：表观遗传药（例如组蛋白脱乙酰基酶抑制剂）；新型蛋白酶体抑制剂；新的免疫调节化合物 细胞周期蛋白依赖性激酶抑制剂；白介素6抑制剂；以及其他实验药物，例如热休克蛋白90抑制剂和针对MM细胞表面受体的单克隆抗体（例如抗CS1和抗CD40）。这些新药中的许多与来那度胺联合使用，都处于临床评估的早期阶段。早期的临床结果令人鼓舞，表明基于来那度胺的新型药物组合在MM患者中有效且普遍耐受。未来的研究将继续评估这些新颖的组合，并帮助确定最佳设置（例如归纳，打捞，