Fouquet Guillemette, Gay Francesca, Boyle Eileen, Bringhen Sara, Larocca Alessandra, Facon Thierry, Leleu Xavier, Palumbo Antonio
Service des maladies du sang, Hôpital Huriez, CHRU, Lille, France.
Myeloma Unit, Division of Hematology, University of Torino, Turin, Italy.
Cancer Treat Res. 2016;169:123-143. doi: 10.1007/978-3-319-40320-5_8.
Multiple myeloma (MM) is a disease of the elderly, with a median age at diagnosis of approximately 70 years old, and more than 30 % of patients aged >75 years. This latter and very elderly population is going to significantly rise in the near future given the increase in life expectancy in Western countries, and, most importantly, global health status of elderly patients is improving, justifying appropriate treatments. Changes in treatment paradigm from the old melphalan-prednisone regimen used since the 1970s to its use as a backbone in a nontransplant setting since the late 1990s have highlighted different subgroups in elderly MM. Some "elderly" patients could be treated like transplant eligible patients, more likely those aged between 65 and the early 70; while a second group would rather be referred to current approved treatment regimens for the non-transplant setting. A dose-intensity approach seems reasonable for this group, aiming for the best response, eventually the complete response (CR) or even minimal residual disease (MRD). The advent of novel agents such as thalidomide, bortezomib, and most recently lenalidomide have allowed a major improvement in outcome as compared to historical combinations, and soon the novel class of monoclonal antibodies should help to further improve these patients' survival. Nonetheless, elderly patients are more susceptible to side effects and are often unable to tolerate full drug doses, and thus require lower dose intensity regimens, or novel drugs or combinations with more favourable safety profile. Recent developments in MM have focused on identifying these vulnerable patients through geriatric assessment and novel myeloma scoring system, including the notions of frailty, disability and comorbidities. Eventually, we have reached an era in which we should be able to provide individualized treatment strategies and drug doses-"tailored therapy"-to improve tolerability and optimize efficacy and ultimately survival for most elderly MM patients.
多发性骨髓瘤（MM）是一种老年疾病，诊断时的中位年龄约为70岁，超过30%的患者年龄大于75岁。鉴于西方国家预期寿命的增加，这一年龄较大且非常高龄的人群在不久的将来将显著增加，而且，最重要的是，老年患者的全球健康状况正在改善，这为适当的治疗提供了依据。治疗模式已从20世纪70年代以来使用的旧美法仑-泼尼松方案转变为自20世纪90年代末以来在非移植环境中作为基础方案使用，这凸显了老年MM患者中的不同亚组。一些“老年”患者可以像适合移植的患者一样接受治疗，更可能是年龄在65岁至70岁出头的患者；而另一组患者则更倾向于采用目前批准的非移植环境治疗方案。对于这一组患者，剂量强度方法似乎是合理的，目标是获得最佳反应，最终达到完全缓解（CR）甚至微小残留病（MRD）。与传统联合用药相比，沙利度胺、硼替佐米以及最近的来那度胺等新型药物的出现使治疗结果有了重大改善，而且很快新型单克隆抗体类药物应有助于进一步提高这些患者的生存率。尽管如此，老年患者更容易出现副作用，往往无法耐受全剂量药物，因此需要较低剂量强度的方案，或使用安全性更好的新型药物或联合用药。MM领域的最新进展集中在通过老年评估和新型骨髓瘤评分系统来识别这些脆弱患者，包括虚弱、残疾和合并症的概念。最终，我们已经进入了一个能够为大多数老年MM患者提供个体化治疗策略和药物剂量——“量身定制疗法”——以提高耐受性、优化疗效并最终提高生存率的时代。
