Unità Operativa Complessa di Ematologia, Dipartimento Oncoematologico, Azienda Ospedaliera di Cosenza, Viale della Repubblica, 87100 Cosenza, Italy.
Expert Opin Emerg Drugs. 2012 Sep;17(3):407-38. doi: 10.1517/14728214.2012.713345.
Survival in multiple myeloma (MM) has improved significantly in the past 10 years due to new treatments, such as thalidomide and lenalidomide (immunomodulatory drugs or IMiDs) bortezomib and advances in supportive care. Nevertheless, almost all MM patients show disease relapse and develop drug resistance.
The authors review the therapeutic approach for untreated MM patients. Furthermore, the prognostic stratification of patients and the proposed risk-adapted strategy are discussed. Finally, preclinical and clinical data regarding newer antimyeloma agents, currently undergoing examination such as proteasome inhibitors (PIs, carfilzomib), IMiDs (pomalidomide), epigenetic agents (histone deacetylase inhibitors vorinostat and panobinostat), humanized monoclonal antibodies (elotuzumab and MOR03087) and targeted therapies (inhibitors of NF-κB, MAPK, HSP90 and AKT) are reported.
MM patient outcome has remarkably improved due to the use of three to four drug combination therapies including PIs and IMiDs, which target the tumor in its bone marrow microenvironment, however MM treatment remains challenging. The use of high-throughput techniques has allowed to discover new insights into MM biology. The identification of candidate therapeutic targets and availability of respective investigative agents will allow for a substantial progress in the development and implementation of personalized medicine in MM.
由于新的治疗方法,如沙利度胺和来那度胺(免疫调节药物或 IMiD)硼替佐米以及支持性护理的进步,多发性骨髓瘤(MM)患者的生存状况在过去 10 年中得到了显著改善。尽管如此,几乎所有 MM 患者都出现疾病复发并产生耐药性。
作者回顾了未经治疗的 MM 患者的治疗方法。此外,还讨论了患者的预后分层和拟议的风险适应策略。最后,报告了关于新型抗骨髓瘤药物的临床前和临床数据,这些药物目前正在接受检查,如蛋白酶体抑制剂(PI,卡非佐米)、IMiD(泊马度胺)、表观遗传药物(组蛋白去乙酰化酶抑制剂伏立诺他和帕比司他)、人源化单克隆抗体(依鲁替尼和 MOR03087)和靶向治疗(NF-κB、MAPK、HSP90 和 AKT 抑制剂)。
由于使用了包括 PI 和 IMiD 在内的三到四种药物联合疗法,MM 患者的预后有了显著改善,这些药物靶向肿瘤在骨髓微环境中的作用,然而,MM 治疗仍然具有挑战性。高通量技术的应用使我们对 MM 生物学有了新的认识。候选治疗靶点的鉴定和相应研究性药物的出现,将使个性化医学在 MM 中的发展和应用取得实质性进展。