Recent Advances in the Management of Smoldering Multiple Myeloma

There is remarkable progress in the treatment of multiple myeloma (MM) with significant improvement in survival in the past 10 years. Monoclonal gammopathy of undetermined significance (MGUS) and smoldering multiple myeloma (SMM) can evolve into symptomatic multiple myeloma (sy-MM) with organ involvement. SMM has associated with a much higher progression to MM compared to MGUS. In 2014, International Myeloma Working Group (IMWG) reclassified ultra-high-risk smoldering myeloma patients with bone marrow plasma cells > 60% or serum-free light chain ratio (FLCr) > 100 or > 1 focal bone lesion on the magnetic resonance imaging as MM. SMM is a heterogeneous disorder with probability for progression to myeloma up to 50% in the first 5 years. Several risk models and clinical features have been identified to stratify the risk of progression to MM. Thanks to advances in our understanding of the genomic profile of MM, there are several ongoing clinical trials, and genomic studies are being done to assess the risk of progression to MM and early intervention. There is still no standard criterion regarding when to start therapy. This review discusses identifying SMM patients who are at high risk of progression to sy-MM and recent development of new and early treatment strategies and ongoing clinical trials for these high-risk SMM patients.