Risk Stratification in Myeloma: Defining Precision in the Genomic Era.

Abstract

Multiple myeloma (MM) exhibits marked clinical heterogeneity, with outcomes ranging from long-term disease control to rapid progression. Accurate identification of high-risk patients is therefore essential. Over the past decades, cytogenetic abnormalities have emerged as key prognostic factors, leading to successive staging systems integrating genomic data. However, limitations in existing models and a lack of standardization have hindered optimal risk assessment. The recent Consensus Genomic Staging (CGS) provides a unified definition of high-risk disease, emphasizing TP53 alterations, biallelic 1p32 deletion, and combinations of intermediate-risk lesions. Validation studies confirm its prognostic value, while also highlighting residual heterogeneity and the concept of functional high-risk disease. Advances in next-generation sequencing, particularly whole-genome sequencing, offer deeper insight into genomic complexity and may further refine stratification. Integration of genomic profiling, gene expression, and minimal residual disease assessment is likely to enhance precision medicine. Ultimately, improved risk stratification is critical to guide risk-adapted therapeutic strategies and improve outcomes in multiple myeloma.