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J Clin Oncol. 2010 Feb 1;28(4):690-7. doi: 10.1200/JCO.2009.22.2257. Epub 2009 Dec 21.

Smoldering (asymptomatic) multiple myeloma: current diagnostic criteria, new predictors of outcome, and follow-up recommendations.

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Hematology Department, Institute of Hematology and Oncology, Institut d'Investigacions Biomèdiques August Pi i Sunyer, Hospital Clínic, University of Barcelona, Barcelona, Spain.



To provide an overview on smoldering (asymptomatic) multiple myeloma (SMM) including current diagnostic criteria, predictors of progression, pattern of progression, and outcome.


A comprehensive review of the literature on risk factors for progression, treatment attempts to delay progression and outcome in patients with SMM.


The risk factors for progression of SMM include: plasma cell mass including M-protein size and percentage of bone marrow clonal plasma cells (BMPC), abnormal free light chain ratio, proportion of phenotypically abnormal BMPC, immunoparesis, evolution pattern (evolving v nonevolving), and pattern of magnetic resonance imaging abnormalities. Most patients with SMM progress with anemia and/or skeletal involvement. Immediate therapy with cytotoxic agents, such as melphalan/prednisone has not resulted in improved outcome. Patients should not be treated until progressive disease with end-organ damage occurs. Increasing anemia is the most reliable indicator of progression.


These recently recognized predictors of outcome may be helpful for better disease monitoring and for investigation of new treatment approaches. Thus, recommendations for follow-up every to 3 to 6 months depending on the risk of progression are suggested, and clinical trials with new noncytotoxic biologically derived agents to delay progression, particularly in high-risk patients, are ongoing.

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