What is the prognosis of monoclonal gammopathy of undetermined significance (MGUS)?

Updated: Dec 29, 2019
  • Author: Suzanne R Fanning, DO; Chief Editor: Emmanuel C Besa, MD  more...
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The annual risk of progression to multiple myeloma (MM), Waldenström macroglobulinemia (WM), amyloidosis (AL), or other lymphoproliferative disorders is approximately 1%. However, the mode and risk of progression vary between IgM MGUS and those with non-IgM MGUS. 

An abnormal serum free light-chain ratio (ratio of kappa to lambda free light chains) and a high serum monoclonal protein (M protein) level (≥1.5 g per deciliter) are risk factors for progression. In IgM MGUS, Kyle et al reported a risk of progression at 20 years of 55% in patients with both risk factors, compared with 41% in those with one risk factor and 19% in patients with neither risk factor. In patients with non-IgM MGUS, the risk of progression at 20 years was 30% in those with both risk factors, 20% in those iwth one risk factor, and 7% in those with neither risk factor. [20]

Rajkumar et al found that the risk of progression in patients with an abnormal serum free light chain (FLC) ratio (kappa-lambda ratio < 0.26 or > 1.65) is independent of the size and type of the serum M protein, and that the relative risk of progression is related to the extent to which the ratio is abnormal. These authors proposed a risk-stratification model for the progression of MGUS, using the combination of the size and type of the M protein and the serum FLC ratio. [23]

Pelzer et al concluded that light-chain MGUS—defined as an abnormal FLC ratio, increase of involved FLC with complete loss of immunoglobulin heavy chain, and absence of a history of lymphoproliferative disease—is a relatively benign condition, and that the monoclonal protein often diisappears over time. In their longitudinal analysis of 75 German patients with light-chain MGUS, after a median observation time of 11.5 years, none of the cases had progressed to light-chain multiple myeloma or other lymphoproliferative disorders. On serial analysis, light-chain MGUS could not be confirmed in 17 of 31 cases (55%), and disappearance of the monoclonal protein was associated with low concentrations of the involved FLC. Although patients with light-chain MGUS had a 1.5-fold increased risk of cancer, overall survival and renal function were not different than in patients with normal FLC. [24]

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