Incidence of Monoclonal Gammopathy of Undetermined Significance and Estimation of Duration Before First Clinical Recognition

Abstract

Objectives: To determine the incidence of monoclonal gammopathy of undetermined significance (MGUS) in the general population and to estimate the duration of occult MGUS before first diagnosis. Methods: To estimate incidence we used innovative methods to exploit the Olmsted County, Minnesota, MGUS prevalence data, along with follow-up from a large cohort of patients with clinically detected MGUS. The prevalence cohort consisted of 21,463 persons systematically screened for the presence or absence of MGUS. The clinical cohort consisted of 7472 patients with MGUS diagnosed at Mayo Clinic from January 1, 1990, to May 13, 2010. The incidence of MGUS was estimated using the prevalence estimates, the rate of MGUS progression, and the death rates from MGUS using Markov chain methods. Results: We estimate that the annual incidence of MGUS in men is 120 per 100,000 population at the age of 50 years and increases to 530 per 100,000 population at the age of 90 years. The rates for women are 60 per 100,000 population at the age of 50 years and 370 per 100,000 population at the age of 90 years. We estimate that 56% of women 70 years of age diagnosed as having MGUS have had the condition for more than 10 years, including 28% for more than 20 years. Corresponding values for men are 55% and 31%, respectively. At 60 years of age, the proportion of prevalent cases that are clinically recognized is 13%. This rate increases to 33% at the age of 80 years. Conclusion: In addition to an accumulation of cases, the age-related increase in prevalence of MGUS is related to a true increase in incidence with age. When first clinically recognized, MGUS has likely been present in an undetected state for a median duration of more than 10 years. M onoclonal gammopathy of undetermined significance (MGUS) is a precursor to multiple myeloma (MM), with a risk of progression of approximately 1% per year. [1][2][3] Monoclonal gammopathy of undetermined significance is defined by a serum monoclonal immunoglobulin level greater than 3 g/dL, less than 10% plasma cells in the bone marrow, and the absence of end-organ damage (hypercalcemia, renal insufficiency, anemia, and bone lesions, collectively referred to as CRAB symptoms) that can be attributed to the monoclonal plasma cell proliferative process. 4 Monoclonal gammopathy of undetermined significance is the most common plasma cell disorder. Indeed, almost 60% of patients presenting with a monoclonal gammopathy at Mayo Clinic have MGUS. In a large population-based screening study conducted among Olmsted County, Minnesota, residents 50 years or older, MGUS was identified in 3.2%; age-adjusted prevalence rates were greater in men (4.0%) than in women (2.7%) and increased with age to 5.3% among persons 70 years or older and to 7.5% among residents 85 years or older. 2 Because MGUS is asymptomatic, only one-third of the MGUS patients detected by screening had been previously recognized through routine clinical care.Although studies conducted so far provide data on the prevalence of MGUS and its re...

Monoclonal IgG in MGUS and multiple myeloma targets infectious pathogens

“…It is well established that the incidence of MGUS and MM increases with age (27). Thus, these conditions are a growing concern in aging populations worldwide.…”

Obesity and risk of monoclonal gammopathy of undetermined significance and progression to multiple myeloma: a population-based study

“…The induction time for MM and other LP diseases is long, and we do not have information on how long each individual has met the criteria for MGUS/LC-MGUS before developing MM or other LP diseases. A US-based screening study on a clinical cohort concluded that when first clinically recognized, MGUS has likely been present in an undetected state for a median duration of .10 years, 43 and the interval from diagnosis of MGUS to diagnosis of MM or related diseases ranges from 1 to 32 years (median, 10.4 years) according to a follow-up study on 241 MGUS patients at Mayo Clinic. 44 Based on these results and the high mean age of the population under study (77 years), it is possible that body weight and composition at time of MGUS/LC-MGUS diagnosis is not a reliable indicator for MM progression, as earlier life physique might be.…”

Multiple myeloma: 2013 update on diagnosis, risk‐stratification, and management

“…MGUS is present in over 3% of the population above the age of 50, and progresses to myeloma or related malignancy a rate of 1% per year [11,12]. Since MGUS is asymptomatic, over 50% of individuals who are diagnosed with MGUS have had the condition for over 10 years before the clinical diagnosis [13]. In some patients, an intermediate asymptomatic but more advanced pre-malignant stage referred to as smoldering multiple myeloma (SMM) can be recognized clinically [14].…”