Ria Roberto, Reale Antonia, Vacca Angelo
Roberto Ria, Antonia Reale, Angelo Vacca, Section of Internal Medicine, Department of Biomedical Sciences and Human Oncology, University of Bari Medical School, I-70124 Bari, Italy.
World J Methodol. 2014 Jun 26;4(2):73-90. doi: 10.5662/wjm.v4.i2.73.
This review summarizes the therapeutic strategies and the drugs actually in development for the management of myeloma patients. Multiple myeloma is caused by the expansion of monoclonal plasma cells and secretion of M-protein (immunoglobulins, Bence Jones protein and free light chains). Multiple myeloma still remains an incurable disease with a high incidence rate in the elderly, despite the introduction of several new therapeutic agents (bortezomib, lenalidomide and thalidomide) which have changed its natural history. The high heterogeneity of this disease leads to large differences in clinical responses to treatments. Thus, the choice of the best treatment is a difficult issue. However, the introduction of new drugs has made it possible to achieve high response rates and good quality responses with long-term disease control. Interactions between tumor cells and their bone marrow microenvironment play a pivotal role in the development, maintenance, and progression of myeloma, inducing also drug resistance. These knowledges have improved treatment options, leading to the approval of new drugs which not only target the malignant cell itself, but also its microenvironment. These agents are in preclinical/early clinical evaluation and they appear to further improve disease control, but their use is still not approved outside of clinical trials.
本综述总结了用于治疗骨髓瘤患者的治疗策略以及目前正在研发的药物。多发性骨髓瘤是由单克隆浆细胞扩增和M蛋白（免疫球蛋白、本-周蛋白和游离轻链）分泌引起的。尽管引入了几种改变其自然病程的新型治疗药物（硼替佐米、来那度胺和沙利度胺），但多发性骨髓瘤在老年人中仍然是一种无法治愈且发病率很高的疾病。这种疾病的高度异质性导致治疗的临床反应存在很大差异。因此，选择最佳治疗方法是一个难题。然而，新药的引入使得实现高缓解率和具有长期疾病控制的良好质量缓解成为可能。肿瘤细胞与其骨髓微环境之间的相互作用在骨髓瘤的发生、维持和进展中起关键作用，同时也诱导耐药性。这些知识改善了治疗选择，促使批准了不仅靶向恶性细胞本身，还靶向其微环境的新药。这些药物正处于临床前/早期临床评估阶段，似乎能进一步改善疾病控制，但在临床试验之外仍未获批使用。
