High-Risk Smoldering Multiple Myeloma: A Review of Controversies in Early Treatment Versus Observation.

Accurate risk stratification is essential as only a subset of patients-defined as high-risk SMM -faces a ≥50% risk of progression within 2 years.

准确的风险分层至关重要，因为只有被定义为高风险SMM的患者群体在2年内面临≥50%的进展风险。

Contemporary approaches integrating clinical variables, dynamic biomarkers, genomic alterations, and immune profiling have improved risk assessment although some limitations remain.

将临床变量、动态生物标志物、基因组改变和免疫表型整合在一起的当代方法已经提高了风险评估的准确性，尽管仍存在一些局限性。

The therapeutic paradigm of SMM is evolving.

SMM的治疗范式正在演变。

Randomized phase III trials have consistently shown that early treatment delays progression to MM.

随机III期试验一致显示，早期治疗可以延迟进展为MM。

Most recently, daratumumab monotherapy became the first approved treatment for high-risk-SMM following the AQUILA trial, which demonstrated a significant progression-free survivalbenefit (hazard ratio[HR], 0.49 [95% CI, 0.36 to 0.67], P < .001) and a trend toward improved overall survival(OS; HR, 0.52 [95% CI, 0.27 to 0.98]) versus observation.

最近，达雷妥尤单抗单药治疗成为首个被批准用于高风险-SMM的治疗，AQUILA试验显示与观察相比，显著提高了无进展生存期（风险比[HR]，0.49 [95% CI，0.36至0.67]，P<.001）并显示出改善总生存期（OS；HR，0.52 [95% CI，0.27至0.98]）的趋势。

This approval challenges the traditional watch-and-wait approach and establishes early intervention as a validated option for selected patients.

这一批准挑战了传统的观察等待方法，并为选定的患者确立了早期干预作为验证过的选择。

However, important uncertainties persist.

然而，仍然存在重要的不确定性。

With modern surveillance and advanced imaging, most progression events are asymptomatic and irreversible end-organ damage is uncommon.

随着现代监测和先进成像技术的应用，大多数进展事件是无症状的，且不可逆的器官损伤较为罕见。

OS benefit from early treatment remains inconclusive, particularly in the era of quadruplet regimens available at MM progression.

早期治疗对总生存期（OS）的益处尚不明确，特别是在多发性骨髓瘤进展时可使用的四联方案时代。

In addition, difficulties in precisely identifying truly high-risk patients raise concerns about overtreatment.

此外，精确识别真正高风险患者所面临的困难引发了过度治疗的担忧。

Emerging data from intensive regimens, bispecific antibodies, and chimeric antigen receptor -T cell therapies suggest that deep and durable responses-and possibly cure-may be achievable in selected patients with high-risk-SMM, but long-term benefit and safety require further study.

来自强化方案、双特异性抗体和嵌合抗原受体T细胞疗法的新兴数据表明，在选择性高风险单克隆免疫球蛋白病（SMM）患者中，深度且持久的反应——可能甚至是治愈——可能是可实现的，但长期益处和安全性需要进一步研究。

In conclusion, following the approval of daratumumab, SMM management should be risk-adapted and patient-centered: observation remains appropriate for some patients, while early treatment should be considered for carefully selected high- and ultrahigh-risk individuals.

总之，在达雷妥尤单抗获批后，SMM的管理应该是风险适应性和以患者为中心的：对于某些患者，观察仍然是适当的，而对于经过仔细挑选的高风险和超高风险个体，则应考虑早期治疗。