肿瘤细胞治疗研究
英文原题：High-Risk Smoldering Multiple Myeloma: A Review of Controversies in Early Treatment Versus Observation.
在daratumumab获批后，SMM的管理应基于风险分层并以患者为中心：对部分患者仍适合观察，而对经过严格筛选的高危和超高危个体应考虑早期治疗。
冒烟型多发性骨髓瘤（SMM）是一种无症状但生物学上异质性的浆细胞疾病，具有进展为多发性骨髓瘤（MM）的可变风险。准确的风险分层至关重要，因为只有一部分患者——定义为高危SMM——在2年内面临≥50%的进展风险。整合临床变量、动态生物标志物、基因组改变和免疫谱分析的当代方法改善了风险评估，尽管仍存在一些局限性。SMM的治疗范式正在演变。随机III期试验一致表明，早期治疗可延缓进展为MM。最近，在AQUILA试验之后，daratumumab单药治疗成为首个获批用于高危SMM的治疗方案，该试验显示与观察相比，无进展生存期显著获益（风险比[HR]，0.49 [95% CI，0.36至0.67]，P < .001），且总生存期（OS）有改善趋势（HR，0.52 [95% CI，0.27至0.98]）。这一获批挑战了传统的观察等待策略，并将早期干预确立为特定患者的经验证选项。然而，重要的不确定性仍然存在。随着现代监测和先进影像学，大多数进展事件是无症状的，不可逆的终末器官损害不常见。早期治疗的OS获益仍无定论，尤其是在MM进展时可获得四联方案的时代。此外，精确识别真正高危患者的困难引发了对过度治疗的担忧。来自强化方案、双特异性抗体和CAR-T 细胞疗法的新兴数据表明，在高危SMM的特定患者中，深度且持久的缓解——甚至可能治愈——是可以实现的，但长期获益和安全性需要进一步研究。总之，在daratumumab获批后，SMM管理应基于风险分层并以患者为中心：对部分患者而言观察仍是合适的，而对于经过仔细筛选的高危和超高危个体，应考虑早期治疗。
Smoldering multiple myeloma (SMM) is an asymptomatic but biologically heterogeneous plasma cell disorder with a variable risk of progression to multiple myeloma (MM). 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. Contemporary approaches integrating clinical variables, dynamic biomarkers, genomic alterations, and immune profiling have improved risk assessment although some limitations remain. The therapeutic paradigm of SMM is evolving. Randomized phase III trials have consistently shown that early treatment delays progression to MM. Most recently, daratumumab monotherapy became the first approved treatment for high-risk-SMM following the AQUILA trial, which demonstrated a significant progression-free survival benefit (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. This approval challenges the traditional watch-and-wait approach and establishes early intervention as a validated option for selected patients. However, important uncertainties persist. With modern surveillance and advanced imaging, most progression events are asymptomatic and irreversible end-organ damage is uncommon. OS benefit from early treatment remains inconclusive, particularly in the era of quadruplet regimens available at MM progression. In addition, difficulties in precisely identifying truly high-risk patients raise concerns about overtreatment. 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. 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.
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