While observation is the current standard of care for smoldering multiple myeloma (sMM), emerging evidence suggests that early therapeutic intervention may delay progression and improve outcomes especially for high-risk patients. A systematic review and meta-analysis of randomized clinical trials was performed according to the PRISMA guidelines in order to evaluate the effect of treatment compared to observation in outcomes of patients with sMM. Five studies (7 articles) involving 844 patients with intermediate or high risk sMM and comparing treatment to observation or placebo were deemed eligible. All studies reported progression-free survival results, with progression defined as time to active myeloma (without high heterogeneity, I2 = 42%, p = 0.14). A statistically significant 60% reduced pooled risk for disease progression or death (HR = 0.40, 95%CI:0.29–0.55) was revealed for patients who underwent treatment compared to those who did not. An exploratory sensitivity analysis involving 3 trials with only observation in the control group, revealed a 66% lower risk for disease progression or death (HR = 0.34, 95%CI: 0.21–0.56) for patients in the treatment group compared to the control group. Furthermore, time-to-progression was reported in 3 studies; the pooled effect estimate revealed a statistically significant 58% reduced risk for progression to symptomatic MM (HR = 0.42, 95%CI: 0.29–0.61) for patients who underwent treatment compared to those who did not. Only 2 trials reported mature overall survival outcomes, and the pooled effect estimate showed a 45% lower risk for death (HR = 0.55, 95%CI: 0.37–0.82) for sMM patients who received treatment compared to those on observation. Regarding safety, the odds for serious adverse events for those on treatment was as 3.5 times as high (OR = 3.53, 95%CI: 1.14–10.91) compared to those on observation or placebo. In conclusion, this meta-analysis highlights the significant benefits of early treatment in selected patients with sMM, across key clinical outcomes. However, close monitoring is essential for the management of treatment-related toxicities.
尽管观察是目前冒烟型多发性骨髓瘤（sMM）的标准处理方式，但新出现的证据表明，早期治疗干预可能会延缓疾病进展并改善预后，尤其是对于高危患者。为评估与观察相比，治疗对sMM患者结局的影响，我们根据PRISMA指南对随机临床试验进行了系统综述和荟萃分析。共纳入5项研究（7篇文章），涉及844例中危或高危sMM患者，比较了治疗与观察或安慰剂的效果。所有研究均报告了无进展生存期结果，其中进展定义为进展至活动性骨髓瘤的时间（无异质性，I² = 42%，p = 0.14）。分析显示，与未接受治疗的患者相比，接受治疗的患者疾病进展或死亡的风险降低了60%（HR = 0.40，95%CI：0.29–0.55），具有统计学显著性。一项探索性敏感性分析纳入了3项对照组仅为观察的试验，结果显示治疗组患者疾病进展或死亡的风险比对照组降低了66%（HR = 0.34，95%CI：0.21–0.56）。此外，3项研究报告了至疾病进展时间；合并效应估计显示，与未治疗者相比，接受治疗的患者进展至症状性多发性骨髓瘤的风险显著降低了58%（HR = 0.42，95%CI：0.29–0.61）。仅2项试验报告了成熟的总生存期结果，合并效应估计显示，与观察组相比，接受治疗的sMM患者的死亡风险降低了45%（HR = 0.55，95%CI：0.37–0.82）。在安全性方面，治疗组发生严重不良事件的几率是观察组或安慰剂组的3.5倍（OR = 3.53，95%CI：1.14–10.91）。总之，本荟萃分析表明，在选定的sMM患者中，早期治疗在关键临床结局方面具有显著益处。然而，密切监测对于管理治疗相关毒性至关重要。
肿瘤(癌症)患者之家