Salem Karma Z, Ghobrial Irene M
Expert Opin Orphan Drugs. 2015 Apr 12;3(6). doi: 10.1517/21678707.2015.1036740.
Smoldering multiple myeloma (SMM) is a heterogeneous clinical entity that defines patients in the spectrum of disease progression from monoclonal gammopathy of undetermined significance to multiple myeloma (MM). Current standard of care is observation until end organ damage occurs. In spite of this, the scientific community has begun to question whether the strategy of watchful waiting should be replaced with earlier therapeutic intervention with the ultimate goal of preventing clonal heterogeneity and end organ damage.
In this review, we challenge the concept of observation as the best option of therapy in SMM. We present current data on diagnosis, prognostic factors of disease progression and studies that have been conducted to date to determine whether earlier therapeutic interventions will lead to an improvement in overall survival of patients with MM.
If the recommendations of treatment of SMM were to change, the scientific body of evidence would have to overcome four major hurdles: to demonstrate that early intervention leads to prolonged survival and delay in development of end organ damage, that it does not have long-term toxicities, that it is implemented in patients with a high-likelihood of developing myeloma and that it does not lead to the outgrowth of more resistant clones. Only well-designed clinical trials will determine whether cure can be achieved with earlier interventions.
冒烟型多发性骨髓瘤(SMM)是一种异质性临床实体,用于定义处于从意义未明的单克隆丙种球蛋白病到多发性骨髓瘤(MM)疾病进展范围内的患者。当前的治疗标准是观察,直至出现终末器官损害。尽管如此,科学界已开始质疑观察等待策略是否应被早期治疗干预所取代,其最终目标是预防克隆异质性和终末器官损害。
在本综述中,我们对将观察作为SMM最佳治疗选择的概念提出质疑。我们展示了关于诊断、疾病进展预后因素的当前数据,以及迄今为止为确定早期治疗干预是否会改善MM患者总生存期而进行的研究。
如果SMM的治疗建议要改变,科学证据体系将必须克服四个主要障碍:证明早期干预能延长生存期并延缓终末器官损害的发展,证明其没有长期毒性,证明其适用于有高骨髓瘤发生可能性的患者,以及证明其不会导致更具耐药性的克隆的出现。只有精心设计的临床试验才能确定早期干预是否能实现治愈。