How I Treat How I treat smoldering multiple myeloma

Although the last decade has seen the development of effective targeted therapies for patients with multiple myeloma (MM), the clinical utility of targeted therapies has been hampered by the development of drug resistance, clonal evolution, and disease progression, making the quest for cure ever more elusive for MM. However, one may argue that the concept of initiating therapy at the time of symptomatic disease in MM is analogous to initiating therapy in patients with solid tumors only after the development of metastatic disease. Consequently, it may not be surprising that even with the best combinations of agents that are currently available, cure is not achieved for most patients with MM. Therefore, many have explored the question of whether the treatment of the precursor asymptomatic states of MM will lead to the ultimate prevention of progression and cure in MM. MM is consistently preceded by precursor states of monoclonal gammopathy of undermined significance (MGUS) and smoldering MM (SMM). These represent a continuum of progression of the tumor burden in the absence of symptoms or signs of end-organ damage. In this article, we review the current understanding of SMM including biological insights and clinically available risks of determining progression. Current recommendations of therapy continue to be patient observation or enrollment in clinical trials for most of these patients. However, new definitions of active MM and indications of therapy were recently agreed by the International MyelomaWorking Group (IMWG). On the basis of the emerging data of therapy in SMM patients showing evidence of long and durable responses reflected in significantly improved progression-free survival (PFS) and overall survival (OS), it seems reasonable to believe that near-future recommendations for therapy of patients with SMM will become an increasingly important topic. Case description