Clinica di Ematologia, Azienda Ospedaliero-Universitaria Ospedali Riuniti di Ancona, Ancona, Italy.
Clin Lymphoma Myeloma Leuk. 2010 Oct;10(5):353-60. doi: 10.3816/CLML.2010.n.068.
The introduction of new drugs such as thalidomide, lenalidomide, and bortezomib has led to novel treatment strategies and significantly improved the outcome of patients with multiple myeloma (MM). The enhanced knowledge of myeloma pathogenesis has allowed the identification of new therapeutic targets and many clinical trials are either planned or in progress to evaluate these more selective drugs in the near future. The results of these studies, however, will have to be compared with the results of existing novel therapies for the treatment of MM in order to define whether new protocols do not duplicate current new standards and constitute a real improvement. We reviewed the results of a series of phase I, II, III studies with thalidomide, lenalidomide, and bortezomib combinations for newly diagnosed MM in order to define a reasonable standard in terms of activity, efficacy, and toxicity and to have a potentially useful starting point for comparisons with future investigational trials. Three-drug regimens appear to double the complete remission (CR) rate (20%), though regimens containing 4 drugs triple the CR rate (30%), compared with those containing only 2 agents (10%). These improvements in the depth and quality of response translate into a progressive increase in the progression-free survival rate at 2 years (from approximately 54%-62% to 75%, respectively). Conversely, by using additional agents, a marked increase in hematologic toxicity has been described (8%, 28%, and 28% respectively), whereas nonhematologic toxicity appears to be similar (26%, 24%, and 27%, respectively). These results suggest that new trials in the future will constitute significant progress if they can improve on the current relatively favorable efficacy/toxicity ratio. Nonetheless, exciting new combinations in development do hold promise and results from these studies are eagerly awaited.
沙利度胺、来那度胺和硼替佐米等新药的引入带来了新的治疗策略，显著改善了多发性骨髓瘤（MM）患者的预后。对骨髓瘤发病机制的深入了解使得新的治疗靶点得以确定，许多临床试验正在计划或进行中，以便在不久的将来评估这些更具选择性的药物。然而，这些研究的结果将不得不与目前治疗 MM 的新型疗法的结果进行比较，以确定新方案是否不重复当前的新标准，是否构成真正的改进。我们回顾了一系列关于沙利度胺、来那度胺和硼替佐米联合治疗初诊 MM 的 I、II、III 期研究的结果，以确定在活性、疗效和毒性方面的合理标准，并为与未来的研究性试验进行比较提供一个潜在有用的起点。三药方案似乎使完全缓解（CR）率翻了一番（20%），而含 4 种药物的方案则使 CR 率增至三倍（30%），而仅含 2 种药物的方案则为 10%。这些反应深度和质量的改善转化为 2 年无进展生存率的逐渐提高（分别约为 54%-62%至 75%）。相反，通过使用额外的药物，描述了明显的血液学毒性增加（分别为 8%、28%和 28%），而非血液学毒性似乎相似（分别为 26%、24%和 27%）。这些结果表明，如果新的试验能够改善当前相对有利的疗效/毒性比，那么未来的试验将取得重大进展。尽管如此，新的令人兴奋的联合开发方案确实有希望，人们急切地等待着这些研究的结果。
