Objective:

To evaluate the independent prognostic value of novel MS-derived proteomic and metabolomic biomarkers in relation to the ISS and R-ISS, and to compare the analytical sensitivity of MS-based methods for MRD monitoring against traditional techniques, specifically focusing on overall survival and progression-free survival outcomes.

Key Findings:

• 19 studies met inclusion criteria from 1,077 records.
• MS-derived signatures, including microenvironmental proteins and dysregulated lipid metabolites, were associated with PFS and OS, indicating their potential as reliable prognostic biomarkers.
• MS-based biomarkers retained independent prognostic significance in multivariate models adjusted for R-ISS.
• MS-MRD detection demonstrated up to 1,000-fold higher sensitivity than traditional methods and identified biochemical relapse 2–11 months earlier.

Interpretation:

Quantitative MS profiling significantly refines MM risk stratification and enhances MRD monitoring, facilitating a shift in clinical practice from reactive to proactive interventions.

Limitations:

• Standardization of bioinformatics pipelines and MS methodologies remains a barrier to routine clinical implementation, impacting the reliability and reproducibility of results.

Conclusion:

MS integration in MM management offers a high-resolution molecular approach for improved prognostic assessment and non-invasive MRD monitoring.