Divisione di Ematologia dell'Università di Torino, Azienda Ospedaliera Universitaria S. Giovanni Battista, Torino, Italy.
Hematology Am Soc Hematol Educ Program. 2009:566-77. doi: 10.1182/asheducation-2009.1.566.
Patients with multiple myeloma aged older than 65 years have traditionally received an oral regimen combining melphalan and prednisone (MP). The introduction of novel agents, such as immunomodulatory drugs and proteasome inhibitors, has substantially changed the treatment paradigm of this disease. Five randomized phase III studies, comparing MP plus thalidomide (MPT) versus MP, have shown that MPT increased time to progression (TTP); however, only two of these five studies showed improvement in overall survival (OS). One randomized study has shown that MP plus bortezomib (MPV) increases both TTP and OS compared with MP. Both MPT and MPV are now regarded as the new standards of care for elderly patients. Other promising results have been reported with MP plus lenalidomide or lenalidomide plus dexamethasone, or the combination of cyclophosphamide, thalidomide, and dexamethasone. Reduced-intensity transplantation can be an option for some patients, especially when novel agents are incorporated into pre-transplant induction and post-transplant consolidation. For patients aged older than 75 years a gentler approach should be used, and doses of standard MPT or MPV should be reduced. An accurate management of treatment-related adverse events with prompt dose-reduction can greatly reduce the rate of early discontinuation and significantly improve treatment efficacy. The choice of treatment should be tailored according to the patient's biologic age and comorbidities, and the expected toxicity profile of the regimen.
传统上，年龄大于 65 岁的多发性骨髓瘤患者接受口服联合马法兰和泼尼松（MP）治疗方案。新型药物的出现，如免疫调节剂和蛋白酶体抑制剂，已经极大地改变了这种疾病的治疗模式。五项比较 MP 联合沙利度胺（MPT）与 MP 的随机 III 期研究表明，MPT 增加了无进展生存期（TTP）；然而，这五项研究中只有两项显示总生存期（OS）有所改善。一项随机研究表明，与 MP 相比，MP 联合硼替佐米（MPV）增加了 TTP 和 OS。MPT 和 MPV 现在都被认为是老年患者的新标准治疗方法。其他有前途的结果已经在 MP 联合来那度胺或来那度胺联合地塞米松，或环磷酰胺、沙利度胺和地塞米松联合方案中报道。对于一些患者，尤其是在新型药物被纳入移植前诱导和移植后巩固治疗时，降低强度的移植可能是一种选择。对于年龄大于 75 岁的患者，应采用更温和的方法，减少标准 MPT 或 MPV 的剂量。通过及时减少剂量来准确管理治疗相关的不良反应，可以大大降低早期停药率，并显著提高治疗效果。治疗方案的选择应根据患者的生物学年龄和合并症以及方案的预期毒性特征进行个体化。
