Next Generation Sequencing in the Diagnosis of Multiple Myeloma

Multiple myeloma (MM) is a biologically and clinically heterogeneous plasma cell malignancy characterized by clonal expansion in the bone marrow and a highly variable clinical course. Despite major therapeutic advances, MM remains incurable, largely due to the associated genomic complexity, clonal evolution, and the emergence of treatment resistance. In this context, next-generation sequencing (NGS) has emerged as a transformative tool for improving disease characterization, risk stratification, and clinical management. This review summarizes current evidence on the application of NGS technologies, including whole-exome sequencing, whole-genome sequencing, and targeted gene panels-in the diagnosis, prognostic assessment, and monitoring of MM. Genomic profiling has consistently revealed recurrent alterations in key driver genes, copy number abnormalities, and structural variants that underlie disease heterogeneity and influence clinical outcomes. In addition to baseline characterization, NGS enables high-resolution analysis of clonal architecture and evolution, offering critical insights into mechanisms of relapse and therapeutic resistance. Importantly, NGS-based assessment of minimal residual disease (MRD) has demonstrated superior sensitivity compared with conventional techniques, providing a powerful prognostic marker and a promising tool for treatment monitoring and response-adapted strategies. Indeed, by integrating genomic and MRD data, NGS supports a more precise and dynamic approach to patient management. Overall, the growing body of evidence highlights NGS as a central component of precision medicine in multiple myeloma. Continued efforts toward standardization, validation of emerging biomarkers, and clinical implementation of sequencing-guided strategies are expected to enhance personalized treatment further and improve patient outcomes.