Mol Diagn Ther. 2026 Mar 30. doi: 10.1007/s40291-026-00836-7. Online ahead of print.
ABSTRACT
Plasma cell disorders range from indolent precursors to aggressive malignancies, with multiple myeloma as the most common malignant form. Multiple myeloma biology is highly complex and driven by genomic heterogeneity. Although recent genomic advances offer increasingly precise treatment strategies, routinely used conventional diagnostic methods sometimes fail to reflect the evolution of up-to-date multiple myeloma risk stratification models, and the implementation of genomic discoveries into clinical guidelines is hindered. We reviewed the current state and emerging roles of genomic diagnostics in multiple myeloma and related conditions, emphasizing the clinical utility. We summarized clinical presentation and diagnostic criteria, mapped the mutational landscape across disease stages, and tracked the evolution of risk stratification from clinical staging to integrated genomic models. We also highlighted recent recommendations that incorporate a quantitative assessment of cytogenetic abnormalities and tumor suppressor gene mutations. Further, we compared routinely used and state-of-the-art technologies including fluorescence in situ hybridization, targeted gene panels, whole-exome and whole-genome sequencing, long-read platforms, optical genome mapping, and analyses of circulating tumor DNA, focusing on their strengths, limitations, and complementary roles in the baseline work-up, longitudinal monitoring, and detection of resistance. Last, we discussed practical barriers to implementation and proposed a framework for proactive integration of novel approaches into clinics. In summary, comprehensive genomic profiling is becoming central to modern multiple myeloma diagnostics and a key step for precise and personalized medicine that will, if integrated into routine care, enable a more precise risk assessment, earlier detection of relapse, and improved therapy selection.
PMID:41910939 | DOI:10.1007/s40291-026-00836-7
