Management of monoclonal gammopathy of undetermined significance (MGUS) and smoldering multiple myeloma (SMM)

Abstract

Monoclonal gammopathy of undetermined significance (MGUS) is defined as a serum M protein level of less than 3 g/dL, less than 10% clonal plasma cells in the bone marrow, and the absence of end-organ damage. The prevalence of MGUS is 3.2% in the white population but is approximately twice that high in the black population. MGUS may progress to multiple myeloma, AL amyloidosis, Waldenström macroglobulinemia, or lymphoma. The risk of progression is approximately 1% per year, but the risk continues even after more than 25 years of observation. Risk factors for progression include the size of the serum M protein, the type of serum M protein, the number of plasma cells in the bone marrow, and the serum free light chain ratio. Smoldering (asymptomatic) multiple myeloma (SMM) is characterized by the presence of an M protein level of 3 g/dL or higher and/or 10% or more monoclonal plasma cells in the bone marrow but no evidence of end-organ damage. The overall risk of progression to a malignant condition is 10% per year for the first 5 years, approximately 3% per year for the next 5 years, and 1% to 2% per year for the following 10 years. Patients with both MGUS and SMM must be followed up for their lifetime.

Figure 1. Prevalence of MGUS According to Age

The bars represent 95% confidence intervals. Ages greater than 90 years have been collapsed to 90 years. MGUS = monoclonal gammopathy of undetermined significance. From Kyle RA et al. N Engl J Med. 2006.[9] Copyright © 2006 by the Massachusetts Medical Society. All rights reserved.

Figure 2. Rate of Development of Multiple Myeloma or Related Disorders in 241 Patients With Monoclonal Gammopathy of Undetermined Significance

From Kyle RA et al. Mayo Clinic Proc. 2004.[20] Used with permission.

Figure 3. Probability of Progression among 1384 Residents of Southeastern Minnesota in Whom Monoclonal G ammopathy of Undetermined Significance (MGUS) was Diagnosed from 1960 through 1994

The curve shows the probability of progression of MGUS to multiple myeloma, IgM lymphoma, primary amyloidosis, macroglobulinemia, chronic lymphocytic leukemia, or plasmacytoma (115 patients). The bars show 95% confidence levels. Modified from Kyle RA et al. N Engl J Med. 2002.[43] Copyright © 2002 by the Massachusetts Medical Society. All rights reserved. Used with permission.

Figure 4. Probability of Progression to Active Multiple Myeloma or Primary Amyloidosis in Patients with Smoldering Multiple Myeloma

Bars denote 95% confidence levels. From Kyle RA et al. N Engl J Med. 2007.[43] Copyright © 2007 by the Massachusetts Medical Society. All rights reserved.