Ciolli Stefania
Department of Hematology, Azienda Ospedaliera Careggi, Florence, Italy.
Clin Cases Miner Bone Metab. 2012 Sep;9(3):150-2. Epub 2012 Dec 20.
Multiple myeloma accounts for 10% of all hematologic cancers. Median age at diagnosis is 69 years for men and 72 years for women. The incidence of MM has remained relatively stable, but the associated mortality has declined since the early 1990s. The knowledge acquired about the bone marrow microenvironment in MM and the availability of new drugs has significantly improved patients survival in the past 10 years. Immunomodulatory drugs (thalidomide, lenalidomide) and proteasome inhibitors (bortezomib, carfilzomib) can induce apoptosis of myeloma plasma cells and suppress cytokine release and metabolic ways which sustain the disease. These novel agents demonstrate substantial activity either alone or as part of a range of combination regimens. MM therapy is now based on 1 or 2 new drugs plus standard chemotherapy. Induction is patient tailored and first of all it depends on eligibility for stem-cell transplantation and key presenting features of the patients and the disease. Noteworthy, novel agent-based combination therapies may overcome most of poor prognostic factors. Up to 80% of newly diagnosed MM patients present with osteopenia, osteolysis and fractures. Thalidomide, lenalidomide and bortezomib have a beneficial effect on myeloma-related bone disease. Thalidomide reduces bone resorption, lenalidomide and bortezomib inhibit osteoclast growth and survival, and specifically target key factors in osteoclastogenesis, preventing development of osteolytic lesions. Noteworthy, new therapies offer higher complete response rates than previously reported with standard regimens.
多发性骨髓瘤占所有血液系统癌症的10%。男性诊断时的中位年龄为69岁,女性为72岁。多发性骨髓瘤的发病率一直相对稳定,但自20世纪90年代初以来,其相关死亡率有所下降。在过去10年中,对多发性骨髓瘤骨髓微环境的认识以及新药的出现显著提高了患者的生存率。免疫调节药物(沙利度胺、来那度胺)和蛋白酶体抑制剂(硼替佐米、卡非佐米)可诱导骨髓瘤浆细胞凋亡,抑制维持疾病的细胞因子释放和代谢途径。这些新型药物单独使用或作为一系列联合治疗方案的一部分均显示出显著活性。目前多发性骨髓瘤的治疗基于1种或2种新药加标准化疗。诱导治疗是根据患者情况量身定制的,首先取决于干细胞移植的适用性以及患者和疾病的关键表现特征。值得注意的是,基于新型药物的联合治疗可能克服大多数不良预后因素。高达80%的新诊断多发性骨髓瘤患者存在骨质减少、骨溶解和骨折。沙利度胺、来那度胺和硼替佐米对骨髓瘤相关骨病有有益作用。沙利度胺减少骨吸收,来那度胺和硼替佐米抑制破骨细胞生长和存活,并特异性靶向破骨细胞生成中的关键因子,防止溶骨性病变的发展。值得注意的是,新疗法的完全缓解率高于先前报道的标准化疗方案。