Prevalence of Monoclonal Gammopathy of Undetermined Significance: A Systematic Review

Abstract

M onoclonal gammopathy of undetermined significance (MGUS) is a premalignant, asymptomatic disorder characterized by monoclonal plasma cell proliferation in bone marrow with absence of end-organ damage. 1 Although historically considered a benign condition, patients with MGUS have a lifelong risk of multiple myeloma, an incurable plasma cell malignancy with a median survival of approximately 4 to 5 years. [2][3][4] Patients with MGUS are also at risk of related disorders, such as light-chain amyloidosis and macroglobulinemia. Conditions such as osteoporosis, hip fractures, and peripheral neuropathy are also associated with MGUS. 5 The rate at which MGUS progresses to multiple myeloma or a related disorder is 1% per year. 6,7 The probability of progression at 25 years of follow-up is approximately 30%. However, after accounting for competing causes of death, true life-time probability of progression is lower (11%). 8 The risk of progression with MGUS does not diminish over time Monoclonal gammopathy of undetermined significance (MGUS) is a premalignant plasma cell disorder that is associated with a lifelong risk of multiple myeloma. We conducted a systematic review of all studies investigating the prevalence and incidence of MGUS in the online database PubMed. The review was conducted from January 6, 2009, through January 15, 2010. The following MeSH search headings were used: monoclonal gammopathy, benign and prevalence; monoclonal gammopathy, benign and incidence; paraproteinemia and prevalence; and paraproteinemia and incidence. Articles were limited to those written in English and published by January 2009. Fourteen studies that met prespecified criteria were included and systematically assessed to identify the most accurate prevalence estimates of MGUS based on age, sex, and race. On the basis of our systematic review, we estimate that the crude prevalence of MGUS in those older than 50 years is 3.2% in a predominantly white population. Studies in white and Japanese populations demonstrate a clear increase in prevalence with age. The prevalence is also affected by sex: 3.7% and 2.9% in white men and women, respectively; and 2.8% and 1.6% in Japanese men and women, respectively. Additionally, MGUS is significantly more prevalent in black people (5.9%-8.4%) than in white people (3.0%-3.6%). We conclude that MGUS is a common premalignant plasma cell disorder in the general population of those older than 50 years. The prevalence increases with age and is affected by race, sex, family history, immunosuppression, and pesticide exposure. These results are important for counseling, clinical care, and the design of clinical studies in high-risk populations. and persists even in patients whose condition has remained stable for decades. 7,9 This fixed risk of progression regardless of duration of disease suggests a random 2-hit model of progression rather than a cumulative damage accumulation model in which the risk of progression would be expected to increase with duration of MGUS. The main risk factors for progressio...

Prior Autoimmune Disease and Risk of Monoclonal Gammopathy of Undetermined Significance and Multiple Myeloma: A Systematic Review

“…For example, it is possible that an individual with unclear symptoms was seen by a doctor and workup led to the diagnosis of an autoimmune disorder, and subsequent additional work-up led to the diagnosis of MGUS. Because 3% of the population above the age of 50 years has been reported to have MGUS, the risk for this phenomenon is not trivial (64). On the other hand, prior studies have stratified for latency and found associations between autoimmune conditions and subsequent MGUS to be significant even when latency intervals have been restricted to 5þ years.…”

Laboratory testing requirements for diagnosis and follow-up of multiple myeloma and related plasma cell dyscrasias

“…MGUS is usually detected as an incidental finding when protein electrophoresis is done as part of laboratory studies for a wide range of symptoms [7]. It is a common disorder with a prevalence of 3%-4% in the Caucasian population over the age of 50 [8], occurs more frequently in men than women, and is at least 2-fold more prevalent in Africans and African Americans compared to Caucasians [9]. By definition the monoclonal protein is < 30 g/L (3 g/dL) and bone marrow (if performed) contains < 10% monoclonal plasma cells.…”

Incidence, clinical course, and prognosis of secondary monoclonal gammopathy of undetermined significance in patients with multiple myeloma

“…[1][2][3] It is present in 3%-4% of the general population over the age of 50 years. 4 The prevalence of MGUS increases with age [5][6][7][8][9] and toxin exposure. 10 MGUS progresses to multiple myeloma (MM) or related malignancy at a rate of 1% per year.…”