Moving From Cancer Burden to Cancer Genomics for Smoldering Myeloma: A Review

IMPORTANCE: All patients who develop multiple myeloma have a preceding asymptomatic expansion of clonal plasma cells, clinically recognized as monoclonal gammopathy of undetermined significance (MGUS) or smoldering multiple myeloma (SMM). During the past decade, significant progresses have been made in the smoldering multiple myeloma (SMM) classification and risk stratification. OBSERVATIONS: Here, we summarize and discuss current clinical challenges and available models for risk stratification in the setting of SMM. Thanks to several novel more effective and less toxic drugs, these aspects are increasingly becoming important to identify patients eligible for early treatment. However, all proposed criteria were built around indirect markers of disease burden, and therefore they are generally able to identify a fraction of SMM patients where both the transformation into multiple myeloma and the genomic subclonal diversification are already happening. In contrast, next generation sequencing approaches have the potential to identify myeloma precursor disease that will progress even before the major clonal expansion and progression, providing a potential base for a more effective and better precision regarding the optimal timing of treatment initiation. CONCLUSIONS AND RELEVANCE: Thanks to modern technologies, in the near coming future, prognostic models derived from genomic signatures independent from the disease burden will allow to better identify the optimal timing to treat a plasma cell clonal disorder at the very early stages, when the chances of eradication are higher.