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Machine Learning-Based Predictive Model for Risk Stratification of Multiple Myeloma from Monoclonal Gammopathy of Undetermined Significance Resumen: Monoclonal Gammopathy of Undetermined Significance (MGUS) is a precursor to hematologic malignancies such as Multiple Myeloma (MM) and Waldenström Macroglobulinemia (WM). Accurate risk stratification of MGUS patients remains a clinical and computational challenge, with existing models often misclassifying both high-risk and low-risk individuals, leading to inefficient healthcare resource allocation. This study presents a machine learning (ML)-based approach for early prediction of MM/WM progression, using routinely collected hematological data, which are selected based on clinical relevance. A retrospective cohort of 292 MGUS patients, including 7 who progressed to malignancy, was analyzed. For each patient, a feature descriptor was constructed incorporating the latest biomarker values, their temporal trends over the previous year, age, and immunoglobulin subtype. To address the inherent class imbalance, data augmentation techniques were applied. Multiple ML classifiers were evaluated, with the Support Vector Machine (SVM) achieving the highest performance (94.3% accuracy and F1-score). The model demonstrates that a compact set of clinically relevant features can yield robust predictive performance. These findings highlight the potential of ML-driven decision-support systems in electronic health applications, offering a scalable solution for improving MGUS risk stratification, optimizing clinical workflows, and enabling earlier interventions. |