Chanan-Khan Asher Alban, Lee Kelvin
Department of Medicine, Department of Pharmacology and Therapeutics, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, NY 14263, USA.
Clin Lymphoma Myeloma. 2007 Apr;7 Suppl 4:S163-9. doi: 10.3816/clm.2007.s.018.
The availability of new agents for multiple myeloma (MM) provides an opportunity to further improve response rates through the development of new combination regimens. Such new agents include pegylated liposomal doxorubicin (PLD) and the immunomodulatory drugs thalidomide and lenalidomide, all of which have demonstrated efficacy and safety in the treatment of newly diagnosed and relapsed/refractory MM. Based on their complementary mechanisms of action and nonoverlapping toxicity profiles, PLD and the immunomodulatory drugs might provide incremental benefits when used in combined treatment regimens. Thus, they have been evaluated in clinical studies that combine PLD/vincristine/dexamethasone and thalidomide (DVd-T) or PLD/vincristine/dexamethasone and lenalidomide (DVd-R) as well as in a study combining bortezomib with PLD and thalidomide. Results of all these studies have included high overall response rates, with improved rates of complete/near complete response compared with similar regimens that do not include chemotherapy (ie, immunomodulatory drugs plus dexamethasone). This article provides the clinical rationale for the use of PLD in combination with immunomodulatory drugs to treat patients with MM and summarizes the clinical experience with these combinations to date. Notably, the early phase I/II study results have been sufficiently encouraging to warrant further investigation in additional large-scale, phase II/III studies. Future clinical trials should focus on determining the optimal dose and schedule for each of these agents when used in combination and whether the addition of other new agents provides an additional response benefit.
用于多发性骨髓瘤（MM）的新型药物的出现，为通过开发新的联合治疗方案进一步提高缓解率提供了契机。这类新型药物包括聚乙二醇化脂质体阿霉素（PLD）以及免疫调节药物沙利度胺和来那度胺，所有这些药物在治疗新诊断和复发/难治性MM方面均已证明了疗效和安全性。基于其互补的作用机制和不重叠的毒性特征，PLD和免疫调节药物在联合治疗方案中使用时可能会带来额外的益处。因此，它们已在将PLD/长春新碱/地塞米松与沙利度胺（DVd-T）或PLD/长春新碱/地塞米松与来那度胺（DVd-R）联合的临床研究中进行了评估，以及在一项将硼替佐米与PLD和沙利度胺联合的研究中进行了评估。所有这些研究的结果都包括较高的总缓解率，与不包括化疗（即免疫调节药物加地塞米松）的类似方案相比，完全/接近完全缓解率有所提高。本文提供了使用PLD与免疫调节药物联合治疗MM患者的临床依据，并总结了迄今为止这些联合治疗的临床经验。值得注意的是，早期的I/II期研究结果已足够令人鼓舞，值得在更多大规模的II/III期研究中进一步探索。未来的临床试验应侧重于确定这些药物联合使用时每种药物的最佳剂量和给药方案，以及添加其他新型药物是否能带来额外的缓解益处。
