Saade Cynthia, Ghobrial Irene M
Center for Early Detection and Interception of Blood Cancers, Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA; Department of Hematologic Malignancies, Lille University Hospital, Lille, France.
Center for Early Detection and Interception of Blood Cancers, Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Presse Med. 2025 Mar;54(1):104268. doi: 10.1016/j.lpm.2025.104268. Epub 2025 Jan 18.
Monoclonal gammopathy of undetermined significance (MGUS) and smoldering multiple myeloma (SMM) are premalignant stages in the development of multiple myeloma (MM). Advances in detection, risk stratification, and therapeutic intervention have transformed our understanding of disease progression. Sensitive techniques like mass spectrometry have identified smaller monoclonal gammopathies, such as monoclonal gammopathy of indeterminate potential (MGIP), which may precede MGUS. Risk stratification models for MGUS and SMM, including the Mayo Clinic, PETHEMA, 2/20/20, IMWG, and PANGEA models, leverage tumor burden markers and cytogenetic abnormalities to predict prognosis. Genomic studies have revealed mutations, structural changes, and mutational signatures that predict progression. Immune microenvironmental alterations underscore the multifactorial nature of disease evolution, while epigenetics is emerging as a source of tumoral and microenvironmental changes. Therapies for high-risk SMM, including lenalidomide, daratumumab, and next-generation immunotherapies, demonstrate efficacy in delaying progression to MM but raise concerns regarding safety in asymptomatic patients. Future research must refine prognostic models, integrate genomic and immunophenotypic data, and establish consensus on optimal strategies for early intervention. This comprehensive review highlights the biological, clinical, and therapeutic advancements in MM and its precursors, emphasizing the importance of early risk assessment and targeted treatment to improve outcomes.
意义未明的单克隆丙种球蛋白病（MGUS）和冒烟型多发性骨髓瘤（SMM）是多发性骨髓瘤（MM）发展过程中的癌前阶段。检测、风险分层和治疗干预方面的进展改变了我们对疾病进展的理解。像质谱分析这样的灵敏技术已经识别出更小的单克隆丙种球蛋白病，如潜在意义未明的单克隆丙种球蛋白病（MGIP），它可能先于MGUS出现。MGUS和SMM的风险分层模型，包括梅奥诊所模型、PETHEMA模型、2/20/20模型、国际骨髓瘤工作组（IMWG）模型和PANGEA模型，利用肿瘤负荷标志物和细胞遗传学异常来预测预后。基因组研究已经揭示了预测疾病进展的突变、结构变化和突变特征。免疫微环境改变突显了疾病演变的多因素性质，而表观遗传学正成为肿瘤和微环境变化的一个来源。针对高危SMM的治疗方法，包括来那度胺、达雷妥尤单抗和新一代免疫疗法，在延缓进展为MM方面显示出疗效，但引发了对无症状患者安全性的担忧。未来的研究必须完善预后模型，整合基因组和免疫表型数据，并就早期干预的最佳策略达成共识。这篇综述强调了MM及其前驱病变在生物学、临床和治疗方面的进展，强调了早期风险评估和靶向治疗对改善预后的重要性。
