Abstract
Smoldering multiple myeloma (SMM) is an asymptomatic precursor stage of multiple myeloma (MM) characterized by clonal bone marrow plasma cells (BMPC) ≥ 10% and/or M protein level ≥ 30 g/L in the absence of end organ damage. It represents an intermediate stage between monoclonal gammopathy of undetermined significance (MGUS) and symptomatic MM. The risk of progression to symptomatic MM is not uniform, and several parameters have been reported to predict the risk of progression. These include the level of M protein and the percentage of BMPC, the proportion of immunophenotypically aberrant plasma cells, and the presence of immunoparesis, free light-chain (FLC) ratio, peripheral blood plasma cells (PBPC), pattern of serum M protein evolution, abnormal magnetic resonance imaging (MRI), cytogenetic abnormalities, IgA isotype, and Bence Jones proteinuria. So far treatment is still not recommended for SMM, because several trials suggested that patients with SMM do not benefit from early treatment. However, the Mateos et al. trial showed a survival benefit after early treatment with lenalidomide plus dexamethasone in patients with high-risk SMM. This trial has prompted a reevaluation of early treatment in an asymptomatic patient population.
Highlights
Smoldering multiple myeloma (SMM) was first described in 1980 in the New England Journal of Medicine (NEJM) [1]
This purpose of this review is to summarize and evaluate the prognostic factors predicting progression to active MM, to discuss early treatment of patients with SMM, and to provide directions for further investigations
Many investigators performed clinical trials to determine whether early treatment using conventional and novel agents resulted in improved clinical outcomes for patients with SMM, when compared with deferred treatment (Table 2)
Summary
Smoldering multiple myeloma (SMM) was first described in 1980 in the New England Journal of Medicine (NEJM) [1]. Some trials used alkylating agents such as melphalan to evaluate the effect of early treatment on patients with SMM [5,6,7]. They caused obvious toxicity and failed to show a significant benefit. Mateos et al reported the results of their phase III trial and showed that early treatment for patients with high-risk SMM improved overall survival [12]. This prompted a reconsideration of treatment of SMM and the definition the high-risk SMM. This purpose of this review is to summarize and evaluate the prognostic factors predicting progression to active MM, to discuss early treatment of patients with SMM, and to provide directions for further investigations
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