Smoldering (asymptomatic) multiple myeloma: Revisiting the clinical dilemma and looking into the future

Adam J. Waxman, Michael Kuehl, Arun Balakumaran, Brendan Weiss, Ola Landgren

Research output: Contribution to journalReview articlepeer-review

16 Scopus citations


Recent studies show that multiple myeloma (MM) is consistently preceded by an asymptomatic precursor state. Smoldering MM (SMM) is a MM precursor defined by an M-protein concentration ≥ 3 g/dL and/or ≥ 10% bone marrow plasma cells, in the absence of end-organ damage. Compared with individuals diagnosed with monoclonal gammopathy of undetermined significance (MGUS), patients with SMM have a much higher annual risk of developing MM. However, based on clinical observations, the natural history of SMM varies greatly, from stable MGUS-like disease to highly progressive disease. Using conventional clinical markers, SMM patients can be stratified into 3 risk groups. Importantly, because of considerable molecular heterogeneity, we currently lack reliable markers to predict prognosis for individual SMM patients. Furthermore, until recently, potent drugs with reasonable toxicity profiles have not been available for the development of early MM treatment strategies. Consequently, current clinical guidelines emphasize the application of close clinical monitoring followed by treatment when the patient develops symptomatic MM. This review focuses on novel biomarkers, molecular profiles, and microenvironmental interactions of interest in myelomagenesis. We also discuss how the integration of novel biologic markers and clinical monitoring of SMM could facilitate the development of early treatment strategies for high-risk SMM patients in the future.

Original languageEnglish (US)
Pages (from-to)248-257
Number of pages10
JournalClinical Lymphoma, Myeloma and Leukemia
Issue number4
StatePublished - Aug 2010
Externally publishedYes


  • Disease classification
  • Free light chain
  • M-protein
  • MGUS
  • Precursor disease

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research


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