Smoldering Asymptomatic Multiple Myeloma

The point of transition from monoclonal gammopathy of undetermined significance (MGUS) to smoldering multiple myeloma is not sharply defined biologically. By definition, MGUS consists of an M-protein value less than 3 g/dL, bone marrow plasma cell value less than 10%, and absence of anemia, renal insufficiency, hypercalcemia, or skeletal lesions attributable to the neoplastic plasma cell proliferation (Table 84.2). However, if the M-protein value is 3 g/dL or more or the bone marrow contains 10% or more plasma cells, the term smoldering (asymptomatic) multiple myeloma is used (Table 84.2).4 Frequently, a reduction of uninvolved immunoglobulins in the serum and a small amount of M protein in the urine are found. These findings are consistent with multiple myeloma, but anemia, renal insufficiency, and skeletal lesions are not present. That is, there is no evidence of end-organ damage. In addition, the plasma cell labeling index is low.

Smoldering multiple myeloma occurs in approximately 15% of all cases of newly diagnosed multiple myeloma.1 The prevalence estimates of smoldering multiple myeloma are variable because many reports include asymptomatic patients with lytic lesions on skeletal survey. Some exclude skeletal lesions but include patients who have lytic lesions on magnetic resonance imaging. A true prevalence derived from strict criteria for smoldering multiple myeloma is not available. Most patients with smoldering multiple myeloma eventually have progression to symptomatic myeloma, and the risk of progression is higher than with MGUS.1 Some patients may remain stable for many years.46 The median time for progression to symptomatic disease is 1-3 years. One study found only a 20% risk of progression at 6 years, but patients were considered to have smoldering multiple myeloma only if they had no disease progression after 1 year of follow-up.47

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