Unità Operativa Complessa di Ematologia, Dipartimento Oncoematologico, Azienda Ospedaliera di Cosenza, Viale della Repubblica, 87100 Cosenza, Italy.
Expert Opin Biol Ther. 2013 Jun;13 Suppl 1:S1-22. doi: 10.1517/14712598.2013.799132. Epub 2013 May 22.
The development of proteasome inhibitor (PI) and immunomodulatory drugs (IMiDs) and advances in supportive care have considerably changed the treatment paradigm of multiple myeloma (MM) and significantly improved survival. Nevertheless, almost all patients show disease relapse and develop drug resistance.
We review the prognostic stratification and therapeutic strategy for newly diagnosed MM patients. Furthermore, mechanisms of drug resistance are discussed. Data regarding newer drugs, currently undergoing examination, such as PI (carfilzomib, ONX0912, MLN9708, and marizomib), IMiDs (pomalidomide), histone deacetylase inhibitors (vorinostat and panobinostat), kinase inhibitors (temsirolimus, everolimus, and tanespimycin), and immune-based therapies (elotuzumab, siltuximab, MOR03087, and MMBT062) are reported.
The use of three to four drug combination therapies including PI and IMiDs has significantly impacted on MM patient outcome. Moreover, new insights into MM biology from high-throughput technologies and availability of newer and more efficacious drugs will continue to influence our approach to MM treatment. In the immediate future molecular subgroup-specific trials using targeted agents may represent a very important step toward evaluating impact of interfering with relevant signaling pathways in MM. With the continued rapid evolution of progress in this field, MM will become a chronic illness having sustained complete response in a significant number of patients.
蛋白酶体抑制剂(PI)和免疫调节药物(IMiDs)的发展以及支持性护理的进步极大地改变了多发性骨髓瘤(MM)的治疗模式,显著提高了患者的生存率。然而,几乎所有患者都会出现疾病复发并产生耐药性。
我们回顾了新诊断 MM 患者的预后分层和治疗策略。此外,还讨论了耐药机制。目前正在研究的新型药物的数据,如 PI(卡非佐米、ONX0912、MLN9708 和 marizomib)、IMiDs(泊马度胺)、组蛋白去乙酰化酶抑制剂(伏立诺他和帕比司他)、激酶抑制剂(替西罗莫司、依维莫司和坦西莫司)和免疫治疗(埃罗妥珠单抗、西妥昔单抗、MOR03087 和 MMBT062)也有报道。
使用三到四种药物联合治疗方案,包括 PI 和 IMiDs,对 MM 患者的预后有显著影响。此外,高通量技术对 MM 生物学的新认识以及新型、更有效的药物的出现将继续影响我们对 MM 治疗的方法。在不久的将来,针对特定分子亚群的靶向药物试验可能是评估干扰 MM 相关信号通路的重要一步。随着该领域的快速发展,MM 将成为一种慢性病,使大量患者获得持续完全缓解。