Monoclonal gammopathy of undetermined significance (MGUS) consistently precedes multiple myeloma: a prospective study

Landgren, Ola; Kyle, Robert A.; Pfeiffer, Ruth M.; Katzmann, Jerry A.; Caporaso, Neil E.; Hayes, Richard B.; Dispenzieri, Angela; Kumar, Santosh; Clark, Raynell J.; Baris, Dalsu; Hoover, Robert N.; Rajkumar, S. Vincent

doi:10.1182/blood-2008-12-194241

Cited by 945 publications

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“…Almost all patients with myeloma evolve from an asymptomatic pre-malignant stage termed monoclonal gammopathy of undetermined significance (MGUS) [9,10]. 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].…”

Section: Disease Overviewmentioning

confidence: 99%

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

2013

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Disease overviewMultiple myeloma accounts for approximately 10% of hematologic malignancies.DiagnosisThe diagnosis requires 10% or more clonal plasma cells on bone marrow examination or a biopsy proven plasmacytoma plus evidence of associated end‐organ damage. In addition, the presence of 60% or more clonal plasma cells in the marrow is also considered as myeloma regardless of the presence or absence of end‐organ damage.Risk stratificationIn the absence of concurrent trisomies, patients with 17p deletion, t(14;16), and t(14;20) are considered to have high‐risk myeloma. Patients with t(4;14) translocation are considered intermediate‐risk. All others are considered as standard‐risk.Risk‐adapted initial therapyStandard‐risk patients can be treated with lenalidomide plus low‐dose dexamethasone (Rd), or a bortezomib‐containing triplet such as bortezomib, cyclophosphamide, dexamethasone (VCD). Intermediate‐risk and high‐risk patients require a bortezomib‐based triplet regimen. In eligible patients, initial therapy is given for approximately 4 months followed by autologous stem cell transplantation (ASCT). Standard‐risk patients can opt for delayed ASCT if stem cells can be cryopreserved. In patients are not candidates for transplant, initial therapy is given for approximately 12–18 months.Maintenance therapyAfter initial therapy, lenalidomide maintenance is considered for standard‐risk patients who are not in very good partial response or better, while maintenance with a bortezomib‐based regimen should be considered in pateints with intermediate or high‐risk myeloma.Management of refractory diseasePatients with indolent relapse can be treated first with two‐drug or three‐drug combinations. Patients with more aggressive relapse often require therapy with a combination of multiple active agents. Am. J. Hematol. 88:225–235, 2013. © 2013 Wiley Periodicals, Inc.

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Section: Disease Overviewmentioning

confidence: 99%

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

2013

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“…Recent epidemiological studies have demonstrated that MM evolves from a previous premalignant condition in most patients. 1,2 Both MGUS and smoldering MM (SMM) are considered to be precursors of active MM. 3,4 However, the rate of progression of these two premalignant conditions to symptomatic MM differs greatly.…”

Section: Multiple Myeloma (Mm) Is a Malignant Disorder Characterized mentioning

confidence: 99%

SNP-based mapping arrays reveal high genomic complexity in monoclonal gammopathies, from MGUS to myeloma status

et al. 2012

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Genetic events mediating transformation from premalignant monoclonal gammopathies (MG) to multiple myeloma (MM) are unknown. To obtain a comprehensive genomic profile of MG from the early to late stages, we performed high-resolution analysis of purified plasma cells from 20 MGUS, 20 smoldering MM (SMM) and 34 MM by high-density 6.0 SNP array. A progressive increase in the incidence of copy number abnormalities (CNA) from MGUS to SMM and to MM (median 5, 7.5 and 12 per case, respectively) was observed (P ¼ 0.006). Gains on 1q, 3p, 6p, 9p, 11q, 19p, 19q and 21q along with 1p, 16q and 22q deletions were significantly less frequent in MGUS than in MM. Although 11q and 21q gains together with 16q and 22q deletions were apparently exclusive of MM status, we observed that these abnormalities were also present in minor subclones in MGUS. Overall, a total of 65 copy number-neutral LOH (CNN-LOH) were detected. Their frequency was higher in active MM than in the asymptomatic entities (P ¼ 0.047). A strong association between genetic lesions and fragile sites was also detected. In summary, our study shows an increasing genomic complexity from MGUS to MM and identifies new chromosomal regions involved in CNA and CNN-LOH.

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“…The estimated median survival of 4 years was based on overall survival estimates of patients with myeloma in that period. Because the total number of patients in this outcome state is a small fraction of the total living population, the results are expected to be insensitive to 3 . A sensitivity analysis was used to verify this.…”

Section: Death Rate After Progression To MM or Related Malignant Neopmentioning

confidence: 99%

“…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.…”

Section: Introductionmentioning

confidence: 99%

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

Therneau

Kyle

Melton

et al. 2012

Mayo Clinic Proceedings

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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...

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Monoclonal gammopathy of undetermined significance (MGUS) consistently precedes multiple myeloma: a prospective study

Abstract: Monoclonal gammopathy of undetermined significance (MGUS) is a premalig-

Cited by 945 publications

References 22 publications

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

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

SNP-based mapping arrays reveal high genomic complexity in monoclonal gammopathies, from MGUS to myeloma status

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

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