Analysis Multiple Myeloma Risk with Routine Blood Biomarkers¶
Overview¶
Multiple myeloma (MM) is preceded by a preclinical phase spanning decades, yet the absence of scalable, non-specialist tools means that individuals at elevated risk cannot be identified before end-organ damage is established. In a prospective analysis of 299,035 cancer-free UK Biobank participants followed for a median of 12.4 years, during which 768 developed incident MM, we conducted a biomarker-wide association scan across 61 routinely measured blood analytes spanning hematological, protein metabolism, renal, and immune categories.
Markers of protein dysregulation, including elevated total protein, depressed albumin, and a low albumin-to-globulin ratio, showed the strongest preclinical associations, consistent with progressive monoclonal immunoglobulin accumulation and suppression of normal polyclonal synthesis beginning years before diagnosis. These protein signals were accompanied by indicators of erythropoietic suppression, morphological red cell dysregulation, and a coherent shift toward lower neutrophil and higher lymphocyte fractions, collectively reflecting multi-system perturbation across hematopoietic and immune compartments.
Longitudinal trajectory analyses demonstrated that these multi-system deviations are already discernible more than a decade before diagnosis and intensify progressively as the clinical event approaches. Incorporating all significant biomarkers into a clinical risk model improved 10-year MM discrimination from a C-index of 0.684 to 0.744, with the high-risk decile accumulating 0.79% cumulative incidence versus 0.47% under the clinical model alone, providing a practical framework for biomarker-guided MM risk stratification and targeted surveillance using routine clinical tests.
Markers of protein dysregulation, including elevated total protein, depressed albumin, and a low albumin-to-globulin ratio, showed the strongest preclinical associations, consistent with progressive monoclonal immunoglobulin accumulation and suppression of normal polyclonal synthesis beginning years before diagnosis. These protein signals were accompanied by indicators of erythropoietic suppression, morphological red cell dysregulation, and a coherent shift toward lower neutrophil and higher lymphocyte fractions, collectively reflecting multi-system perturbation across hematopoietic and immune compartments.
Longitudinal trajectory analyses demonstrated that these multi-system deviations are already discernible more than a decade before diagnosis and intensify progressively as the clinical event approaches. Incorporating all significant biomarkers into a clinical risk model improved 10-year MM discrimination from a C-index of 0.684 to 0.744, with the high-risk decile accumulating 0.79% cumulative incidence versus 0.47% under the clinical model alone, providing a practical framework for biomarker-guided MM risk stratification and targeted surveillance using routine clinical tests.
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