Risk Stratification in Newly Diagnosed Smoldering Multiple Myeloma

Abstract

Smoldering multiple myeloma (SMM) is an asymptomatic plasma cell disorder characterized by the presence of ≥3 g/dL serum M-protein and/or 10–60% bone marrow plasma cell infiltration with no myeloma-defining event. The risk of progression to active MM is not uniform, and several markers are useful for identifying patients at high risk of progression. The definition of the disease has recently been revisited, and asymptomatic MMs at 80–90% of progression risk at 2 years are now considered to be active MMs candidates for treatment. Although the current standard of care is not to treat, a randomized trial in high-risk SMM patients comparing early treatment versus observation has shown a significant benefit in terms of time to progression and overall survival for early intervention. These findings highlight the need for both more precise biomarkers for accurate risk stratification in order to plan an optimized follow-up according to the risk of progression, as well as confirmatory clinical trials in order to establish whether or not early treatment should become standard of care in high-risk SMM.