Myeloma Institute, Sylvester Comprehensive Cancer Center, Division of Myeloma, University of Miami, Miami, FL, United States of America; Hematology/Oncology fellowship program, University of Miami, Sylvester Comprehensive Cancer Center, Miami, FL, United States of America.
Myeloma Institute, Sylvester Comprehensive Cancer Center, Division of Myeloma, University of Miami, Miami, FL, United States of America.
Blood Rev. 2024 Nov;68:101242. doi: 10.1016/j.blre.2024.101242. Epub 2024 Oct 6.
In the 1960s, through laboratory-based investigations of peripheral blood partnered with detailed clinical annotations, Dr. Waldenström described a condition he called "benign monoclonal gammopathy". These patients were asymptomatic with a detectable monoclonal protein, and did not meet imaging and laboratory criteria for multiple myeloma. In 1978, through observational retrospective review of medical records, Dr. Kyle observed that not all cases of monoclonal gammopathy were benign. He introduced the term monoclonal gammopathy of undetermined significance (MGUS) to describe a condition that may potentially progress to multiple myeloma (MM), highlighting clinical inability in predicting which patients might progress. In 1980, Drs. Kyle and Greipp described 6 cases which did not fit the definitions of MGUS or MM, and they remained asymptomatic after at least 5 years of follow-up; they were proposed to have smoldering multiple myeloma (SMM). Over time, SMM was defined by arbitrary numerical values (≥10 % plasma cells in the bone marrow and serum M-protein concentration ≥ 3 g/dL). Numerous clinical scores have been developed to define high-risk groups for progression to MM. Current statistical models for progression provide only average risk scores, offering limited clinical utility since the risk of progression at an individual level remains unknown. Physician-scientists are focusing on emerging technologies, such as whole genome sequencing, tumor microenvironment analysis, and single-cell RNA sequencing, to understand precursor states at a molecular level. The overarching goal of these technologies is to better characterize monoclonal gammopathy and other myeloma precursor states. This will enable clinicians to provide more precise, individualized risk assessments and ultimately improve patient outcomes. This review outlines the history of MM precursor states, current definitions, challenges in risk stratification models, and the role of emerging technologies in enhancing predictions and outcomes.
20 世纪 60 年代，通过对周边血液的实验室研究，并结合详细的临床注释，瓦尔登斯特伦博士描述了一种他称之为“良性单克隆丙种球蛋白病”的病症。这些患者无症状，可检测到单克隆蛋白，但不符合多发性骨髓瘤的影像学和实验室标准。1978 年，通过对病历的观察性回顾性审查，凯尔博士观察到并非所有单克隆丙种球蛋白病都是良性的。他引入了“意义未明的单克隆丙种球蛋白病（MGUS）”一词来描述一种可能进展为多发性骨髓瘤（MM）的病症，强调了临床预测哪些患者可能进展的能力有限。1980 年，凯尔博士和格里普博士描述了 6 例不符合 MGUS 或 MM 定义的病例，这些病例在至少 5 年的随访后仍然无症状；他们被提议患有冒烟型多发性骨髓瘤（SMM）。随着时间的推移，SMM 的定义由任意数值决定（骨髓中浆细胞≥10%和血清 M 蛋白浓度≥3g/dL）。已经开发了许多临床评分来定义进展为 MM 的高危人群。目前用于进展的统计模型仅提供平均风险评分，由于个体水平的进展风险未知，因此提供的临床实用性有限。医师科学家们专注于新兴技术，如全基因组测序、肿瘤微环境分析和单细胞 RNA 测序，以从分子水平了解前驱状态。这些技术的总体目标是更好地描述单克隆丙种球蛋白病和其他骨髓瘤前驱状态。这将使临床医生能够提供更精确、个体化的风险评估，并最终改善患者的预后。本综述概述了 MM 前驱状态的历史、当前定义、风险分层模型中的挑战，以及新兴技术在增强预测和结果方面的作用。
