Smoldering Multiple Myeloma: To Treat or Not to Treat

Smoldering multiple myeloma (SMM) is an asymptomatic, intermediate stage positioned between the plasma cell disorders of monoclonal gammopathy of undermined significance and overt multiple myeloma (MM). Although the patients with SMM have a higher risk of progression to MM in comparison to their counterparts with monoclonal gammopathy of undermined significance, their clinical course can be highly variable. The standard of care for SMM, irrespective of the risk status, continues to be observation due to paucity of high-level evidence demonstrating survival or quality-of-life benefit with early intervention. With the expanded 2014 criteria for MM utilizing biomarkers, the subset of SMM patients with 70% to 80% risk of progression at 2 years (ultra-high risk SMM) is now categorized as active MM and treated prior to the development of end-organ damage. After exclusion of this group, patients with approximately 50% risk of progression in 2 years are now considered high-risk SMM, and the value of early treatment in this subset can be established only through clinical trials. Despite its limitations, a recent phase III trial (QuiRedex) has shown survival advantage to using lenalidomide and dexamethasone doublet over observation in high-risk SMM. In this article, we review the evolving concepts in the diagnosis, risk stratification, and management of SMM.