Multiple myeloma (MM) evolves over decades, yet robust tools for identifying individuals at risk long before clinical onset remain limited. Using data from 378,930 UK Biobank participants, we systematically characterized the longitudinal dynamics and predictive value of routinely measured "CRAB-like" biomarkers, including hematologic indices, protein metabolism markers, renal function, and serum calcium. Across multivariable models, biomarkers reflecting anemia and protein imbalance (including hemoglobin, red blood cell indices, total protein, albumin, and the albumin/globulin ratio) showed strong and consistent associations with future MM, independent of demographic, lifestyle, clinical, and genetic risk factors. These markers displayed pronounced non-linear dose-response relationships and contributed substantially to 5- and 10-year MM risk discrimination, with the C-index improving from 0.66 to 0.76. Longitudinal analyses revealed progressive shifts in red cell morphology and protein metabolism profiles up to a decade before diagnosis, supporting the existence of a preclinical susceptibility continuum detectable in the general population. Our findings suggest that subtle yet quantifiable deviations in common laboratory tests reflect early microenvironmental changes that precede malignant plasma cell expansion, offering opportunities for risk stratification and targeted surveillance.

翻译：多发性骨髓瘤（MM）的发展历经数十年，然而在临床发病前长期识别高危个体的可靠工具仍然有限。利用英国生物银行378,930名参与者的数据，我们系统性地分析了常规检测的'CRAB样'生物标志物（包括血液学指标、蛋白质代谢标志物、肾功能和血清钙）的纵向动态变化及预测价值。在多变量模型中，反映贫血和蛋白质失衡的生物标志物（包括血红蛋白、红细胞指数、总蛋白、白蛋白及白蛋白/球蛋白比值）与未来MM风险呈现强且一致的关联性，且独立于人口统计学、生活方式、临床及遗传风险因素。这些标志物表现出显著的非线性剂量-反应关系，并对5年及10年MM风险区分度有重要贡献，C指数从0.66提升至0.76。纵向分析显示，在诊断前长达十年期间，红细胞形态和蛋白质代谢谱呈现渐进性改变，支持在普通人群中存在可检测的临床前易感性连续谱。我们的研究结果表明，常规实验室检测中细微但可量化的偏差反映了恶性浆细胞扩增前的早期微环境变化，为风险分层和针对性监测提供了契机。