Prevalence Of Monoclonal Gammopathy Of Undetermined Significance Research Articles

Prevalence of monoclonal gammopathy of undetermined significance in Shenzhen, China

ABSTRACT Background Data on the prevalence of monoclonal gammopathy of undetermined significance (MGUS) in China are very limited. Our aim was to determine the prevalence and clinical characteristics of MGUS in a large Chinese population. Methods This study included 49,220 healthy people who received serum immunofixation electrophoresis (sIFE) and serum protein electrophoresis (SPE) tests. Serum free light chain ratio, immunoglobulin quantification, and other clinically correlates of MGUS were performed for all patients with M-protein. Results A total of 576 MGUS patients were identified by sIFE, with a median age of 58 years and an overall prevalence of 1.17% (95% CI, 1.08–1.27). Among those aged 50 years and older, the prevalence of MGUS was 2.26% (95% CI, 2.04–2.50). The prevalence of MGUS was significantly higher in males than in females (P < 0.05). The median concentration of M-protein was 3.1 g/L, ranging from 0.5 g/L to 25.1 g/L. The M-protein type was IgG in 55.4% of MGUS patients, followed by IgA (31.1%), IgM (9.5%), IgD (0.5%), biclonal (2.3%), and light chain (1.2%). Abnormalities in SPE, FLC ratios, and immunoglobulin levels were observed in 78.3%, 31.1%, and 38.4% of MGUS patients, respectively. Conclusions The prevalence of MGUS is substantially lower in southern China than in whites and blacks.

The Association between Rheumatological Diseases and Monoclonal Gammopathy of Undetermined Significance

Background: Monoclonal Gammopathy of Undetermined Significance (MGUS) is an asymptomatic clonal plasma cell disorder with the risk of progression to multiple myeloma (MM). Studies have shown that patients with rheumatological diseases (RD) are associated with an increased risk of progression of MGUS to MM. RD also exhibit higher prevalence of MGUS compared to the general population. Immunological dysregulation and chronic antigen stimulation from autoimmune activity are proposed mechanisms. We assessed the association between RD and MGUS development in the nationwide Veteran Health Administration database, thereby contributing to a deeper understanding of this relationship and its clinical implications. Methods: Patients with RD diagnosis (≥2 outpatient ICD 9/10 codes or ≥1 inpatient code) from 1999-2021 were included. Exclusions applied to patients with MGUS diagnosis (identified by a published natural language processing model), MM (ICD-9-CM/ICD-10-CM: C90/203.0/C90), non-Hodgkin lymphoma (202.85/C85), Waldenstrom's macroglobulinemia and other B-cell lymphomas (273.3/C88), or an amyloidosis (277/E85) prior to or &amp;lt;6 month of RD diagnosis. The first RD diagnosis was defined as the index date, with index age as the age at RD diagnosis. Follow-up time was from the index date to MGUS diagnosis/death/censoring (12/31/2021) which ever came first. Patients with RD were 1:2 matched to individuals without RD on their follow-up time (and determined their index date/age), followed by matching on their index age (±1 year). The same exclusion criteria were applied to individuals without RD. To account for potential bias due to more frequent care because of comorbidities, the cohort was further stratified by Charlson Comorbidity Index (CCI) at index date (high vs low based on median CCI). CCI was computed using ICD codes to identify diseases diagnosed &amp;lt;5 years before and 1 year after the index date. RD was categorized into antibody (Ab)-mediated and non-antibody (non-Ab) mediated RD. Stratified by CCI (high and low), multivariable logistic regression was conducted to analyze the association between RD (Ab and non-Ab mediated) and MGUS using multivariable-adjusted odds ratio (aOR). The covariates included sex, race (non-Hispanic White, non-Hispanic Black, Hispanic, Other), index age, body mass index (underweight, normal, overweight, obese), marital status (divorced/separated/widow, married, single), rurality (rural, urban), and CCI. Results: We analyzed data of 118,365 veterans; 39,455 had RD (80% non-ab-mediated, 20% Ab-mediated). Mean age was 54 years in both RD and non-RD groups by matching. Most patients were male (88.5% RD, 85.1% non-RD). Racial composition was similar: 56.5% non-Hispanic White, 26.0% non-Hispanic Black, and 6.9% Hispanic in the RD group, and 56.0%, 21.6%, 6.9% respectively in non-RD group. Median CCI was higher in the RD group (1 vs. 0). Most patients were obese (51.7% RD, 42.5% non-RD) or overweight (31.0% RD, 37.2% non-RD). In patients with high CCI (n=64,343), Ab-mediated RD (n=7,326) was associated with increased MGUS risk (aOR 2.1, 95% Confidence Interval [CI] 1.8-2.4, p&amp;lt;.0001) as was non-Ab mediated RD (n=20,830) (aOR 2.0, 95% CI 1.9-2.2, p&amp;lt;.0001) compared to patients without RD (n=36,187). In the low CCI group (n=54,022), non-Ab mediated RD (n=10,738) was associated with an increased risk of MGUS (aOR 4.4, 95% CI 3.3-5.7, p&amp;lt;0.0001) compared to patients without RD (n=42,723). There was not sufficient evidence to show that Ab-mediated RD (n=561) was associated with higher MGUS risk (aOR 2.6, 95% CI 0.49-13.7, p=0.26). Conclusions: In a retrospective cohort of US veterans, RD was associated with a higher incidence of MGUS. Both Ab-mediated and non-Ab mediated RD were associated with a higher risk of MGUS diagnosis in patients with higher burden of comorbidities. In patients with fewer comorbidities, only non-Ab-mediated RD was associated with MGUS, likely due to a small number of patients with Ab-mediated RD. Bias in MGUS assessment should be considered, as patients with RD may undergo more testing, leading to increased detection of MGUS. Future prospective studies are needed to evaluate this association and if presence of the RD increases risk of progression to MM.

Asymptomatic Incidence of Monoclonal Gammopathy of Undetermined Significance and Preclinical Duration to Myeloma Diagnosis: A Modeling Study.

Monoclonal gammopathy of undetermined significance (MGUS) is the premalignant condition of multiple myeloma. Given a lack of population-based screening for MGUS and its asymptomatic nature, the epidemiology of MGUS remains unknown. This study estimated age- and race/ethnicity-specific MGUS incidence and preclinical duration from MGUS to multiple myeloma in the United States. A previously published modeling approach was used to calculate national MGUS incidence using estimates of MGUS prevalence, multiple myeloma incidence, multiple myeloma-specific and all-cause mortality, and population age distribution from the National Health and Nutrition Examination Survey, 1999 to 2004, and Surveillance, Epidemiology, and End Results, 2000 to 2021. The estimated MGUS prevalence was divided by MGUS incidence to obtain preclinical duration of multiple myeloma. MGUS incidence for non-Hispanic White (NHW) populations was 52, 86, 142, and 181 and for non-Hispanic Black (NHB) population was 110, 212, 392, and 570 per 100,000 person-years at ages 50, 60, 70, and 80 years, respectively. The average preclinical duration was 20.5 (95% confidence interval, CI, 16.5-26.1) years for the NHW population and 14.2 (95% CI, 11.5-17.6) years for the NHB population. The cumulative risk of developing MGUS in age 50 to 85 was 2.8% (95% CI, 1.7%-4.2%) for the NHW population and 6.1% (95% CI, 3.8%-10.0%) for the NHB population. NHB populations had a higher MGUS incidence rate at all ages and a shorter preclinical duration of multiple myeloma compared to their NHW counterparts. This study provides insights into the epidemiology of MGUS and enhances our understanding of the natural history of multiple myeloma. See related In the Spotlight, p. 1547.

Prevalence of monoclonal gammopathy of undetermined significance in Eswatini: a population-based study in Africa.

Although monoclonal gammopathy of undetermined significance (MGUS) and multiple myeloma disproportionately affect Black individuals, few epidemiological studies have been conducted on these plasma cell disorders in Africa. Here we describe the prevalence of MGUS in Eswatini and compare our results to the landmark Olmsted County, Minnesota study. Between 2016 and 2017, 13 339 residents of Eswatini participated in the Swaziland HIV Incidence Measurement Survey, from which a nationally representative biorepository was created. Plasma samples were then randomly selected and analyzed for MGUS. MGUS prevalence in Eswatini was compared with that of Olmsted County. In addition, demographic and HIV-related associations with MGUS were assessed. Of the 515 samples randomly selected, the median age was 50 years (range = 35-80 years); 60% were female; and 38.6% were HIV positive, of whom 82.4% were on antiretroviral therapy. We found that 68 participants had evidence of MGUS, for a prevalence of 13.2%. HIV status was not significantly associated with MGUS (odds ratio = 1.05, 95% confidence interval = 0.62 to 1.77), but among HIV-positive individuals, MGUS was less frequent for patients on antiretroviral therapy (adjusted odds ratio = 0.31, 95% confidence interval = 0.11 to 0.82). The prevalence of conventional MGUS was similar between Eswatini and Olmsted County (3.4% vs 3.2%-3.4%), whereas the incidence of light-chain MGUS was significantly greater in Eswatini (12.3% vs 0.8%). Our study suggests that the incidence of MGUS is similar between ethnicities and raises the question of whether the current definition of light-chain MGUS reliably reflects a true monoclonal protein precursor state. Perhaps the current definition of light-chain MGUS may be capturing alternate etiologies, such as untreated HIV infection.

Analyzing the impact of type 1 and type 2 diabetes on patients with monoclonal gammopathy of undetermined significance (MGUS) and multiple myeloma (MM): A retrospective study at a tertiary care center.

e19512 Background: Monoclonal Gammopathy of Undetermined Significance (MGUS) and Multiple Myeloma (MM) are hematologic conditions characterized by demographic and clinical feature variations. Examining the prevalence and outcomes of MGUS and MM in individuals with different types of diabetes is crucial for personalized healthcare. The primary aim of this study was to explore potential differences in prevalence and outcomes between type 1 and type 2 diabetes populations. Methods: A cohort of 193 patients(pts),obtained from a large endocrine clinic in Brooklyn,New York, between 2015 and 2024, comprising 56 pts with MGUS and 137 pts with MM, was analyzed for demographic characteristics, comorbidities (hypertension, hyperlipidemia, chronic kidney disease), Hemoglobin A1C levels, and diabetes type. Fisher’s exact test and chi-square test were employed to assess the statistical significance of associations. Results: The cohort predominantly consisted of Black individuals (93%), with a statistically significant association between race and the conditions (p = 0.036). While gender distribution showed no significant association, a borderline significance was observed in the relationship between the type of diabetes and the conditions (p = 0.061). Age, co-morbidities, and Hemoglobin A1C levels did not exhibit significant associations with MGUS or MM. Conclusions: In conclusion, our preliminary analysis reveals significant associations between race and the potential links between types of diabetes and occurrences of MGUS and MM. Ongoing research aims to expand the cohort, addressing data limitations for a more comprehensive exploration. This study establishes a foundation for understanding and offers insights into personalized healthcare strategies for individuals with MGUS or MM who have diabetes. [Table: see text]

Abstract 3455: Prevalence of monoclonal gammopathy of undetermined significance (MGUS) in a Western Nigerian population

Abstract Monoclonal gammopathy of undetermined significance (MGUS) is a premalignant condition characterized by plasma cell production of monoclonal (M) protein and is a requisite precursor to multiple myeloma (MM). African American (AA) individuals have a two-fold higher incidence of MGUS and MM compared to White individuals. However, data are limited on individuals from Africa, especially using sensitive MGUS detection methods. We examined the prevalence of MGUS in a sample of the general population in Nigeria. Individuals aged 40 and over (n=343) were recruited through health promotion events in Ado-Odo Ota Local Government Area of Ogun State, Nigeria, and provided informed consent, a blood sample, and a short questionnaire. Serum was screened at Mayo Clinic for heavy chain (HC)-MGUS using the matrix-assisted laser desorption/ionization-time of flight (Mass-Fix) assay, which has high sensitivity for detection of M-proteins; serum free light chains (FLC) were also measured. FLC was abnormal if the kappa (&amp;gt;0.26 mg/dL) or lambda (&amp;gt;0.33 mg/dL) light chain (LC) was elevated and FLC ratio (kappa/lambda) was outside the reference range (0.26-3.10). LC-MGUS was defined as an abnormal FLC in the absence of a HC. Age- and sex-adjusted prevalence rates were directly standardized to 2010 United States (US) population for comparison to published studies. Logistic regression was used to examine the association of age, sex, and BMI with HC-MGUS. The mean age of participants was 55 years (SD=10.9), and 74.6% were female. Of these, 216 (63%) had both parents from the Yoruba tribe, 89 (26%) from the Igbo tribe and 38 (11%) from other tribes. Overall, 33 participants (9.6%) had HC-MGUS, with 8 (2.3%) having an M-protein above 0.2 g/dL; 6 (1.7%) had LC-MGUS. HC-MGUS was predominantly IgG isotype (48.5%), followed by IgA (27.3%), biclonal (15.2%) and IgM (9.0%). Prevalence of HC-MGUS was 8.3% for ages 40-49, 7.7% ages 50-69 and 22% ages 70 and above. Standardized to the US population, age and sex adjusted MGUS prevalence ages 50 and older was 17.3% (95% CI: 9.8%-24.9%) and HC-MGUS was 14.7% (95% CI: 7.7%-21.8%), similar to previously published rates of HC-MGUS using Mass-Fix screening of AA individuals (16.5%, 95% CI: 12.2%-20.8%) (PMID: 35316833). In models that included age, sex and BMI, older age was positively associated with HC-MGUS (OR=3.1, 95% CI: 1.1-8.7 for ages 70+ compared to &amp;lt;50), while female sex (OR=0.53, 95% CI: 0.24-1.2) and overweight/obesity (OR=0.34, 95% CI: 0.16-0.75 for BMI &amp;gt; 25 vs. &amp;lt;25) were inversely associated with HC-MGUS. We observed similar prevalence of HC-MGUS at ages 50 and above among Western Nigerian and AA populations when screened using mass-spectrometry. Older age was positively associated with HC-MGUS while overweight and obesity were inversely associated. Studies of MGUS in indigenous African populations may provide insight to unique cancer risk factors compared to other populations. Citation Format: Celine M. Vachon, Cristine Allmer, Danelle Moonen, Aaron Norman, Joselle Cook, Susan Slager, Oluwakemi A. Rotimi, Opeyemi C. De Campos, Titilope M. Dokumu, David Murray, Shaji Kumar, Elizabeth Brown, Linda B. Baughn, Solomon Rotimi. Prevalence of monoclonal gammopathy of undetermined significance (MGUS) in a Western Nigerian population [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3455.

Prevalence of MGUS in Rural Indian Population: Results of Simple (IMAGe-002A) Study

Introduction: The incidence of monoclonal gammopathies is rising across the globe. Although the prevalence of monoclonal gammopathy of undetermined significance (MGUS) has been evaluated in two hospital-based studies in India, no data exists on its prevalence in community-based settings amongst the rural Indian population. Objectives: To determine the prevalence of MGUS in a rural Indian population in a community-based setting. Methods: A cross-sectional study was conducted in an agrarian village in India covering a perimeter of 24.76Km and 4588.3 hectares with an 89.2% population coverage for adults more than 45y spending 12096 man-hours as part of SIMPLe ( Screening Intervention for Myeloma and Prevention of Lifestyl e diseases) study under the aegis of Indian Myeloma Academic Group e (IMAGe) registered vide CTRI/2023/03/051220. For the complete study population, demographic details, medical history, and blood samples were collected after a thorough medical examination. Hemogram, biochemistry (Liver and renal function tests), and serum protein electrophoresis (SPEP) were universally performed in all individuals. Serum immunofixation electrophoresis (SIFE) was performed for those with abnormal SPEP graphs (those with M spike and those with abnormal bulges in beta-2 or gamma region suspicious of MGUS). Patients with monoclonal protein on SPEP or SIFE were further assessed for any features of smoldering/ multiple myeloma. The data was analyzed using JMP ver. 16.0.0. Results: The prevalence of MGUS in the study population was 1.75%. The mean age of individuals with MGUS was 63.4±5.2y with male preponderance (60%). The mean Hb was 12.39±1.8g/dL with none of the patients having any renal dysfunction. None of the patients fit into the criteria for smoldering or multiple myeloma using IMWG criteria. Among those with MGUS, the distribution of Heavy and light chains was IgG - 83.33%, IgA - 16.67% with none having IgM/ IgD paraprotein, Kappa - 50%, and Lambda - 50%. Two individuals only had light chain MGUS. Conclusion: Our study provides a comprehensive description of the prevalence of MGUS in a rural community setting in India. The background prevalence is much less compared to the Western (both USA ~3% and European~5%) population.

Prevalence of Monoclonal Gammopathy of Undetermined Significance in Eswatini: A Study of an African Population

Multiple myeloma and its precursor, monoclonal gammopathy of undetermined significance (MGUS), both occur twice as often within Black populations compared to White populations, suggesting that racial factors may influence the development of MGUS, not the progression from MGUS to malignancy. The landmark epidemiologic study that described the natural history of MGUS was conducted among 21,463 of the 28,000 residents in Olmsted County, Minnesota, a 97% White population, and found the age-standardized prevalence (including light-chain, LC, MGUS) to be 4.2% (Dispenzieri, et al, Lancet, 2010). Although MGUS disproportionately affects Black individuals, few studies have been conducted on MGUS in Africa, and no prior study has evaluated MGUS in a Black African cohort inclusive of both sexes. Using a population-based biorepository from Eswatini, a small country in southern Africa, we further explored the racial disparities related to plasma cell dyscrasias. Our primary objective was to determine the prevalence of MGUS in Eswatini, as compared to that found in Olmsted County. Additionally, we aimed to determine the association between MGUS and HIV status. From 2016 to 2017, over 15,000 individuals from a nationally representative selection of households participated in the Second Eswatini Population-based HIV Impact Assessment survey, SHIMS2 (phia.icap.columbia.edu/countries/eswatini). After providing informed consent, interviews were conducted and blood samples were collected. Samples were tested for HIV, and if positive, also for CD4+ cell counts and the serologic presence of antiretroviral therapy (ART). The remaining plasma aliquots were stored and linked to their de-identified corresponding survey data for future research endeavors. For our current study, all adults over the age of 35 years who had SHIMS2 specimens stored were included in the sampling frame. We randomly selected 515 plasma samples from the sampling frame, with the sample size determined to produce a two-sided 95% confidence interval (CI) with a width of 0.05 and power &amp;gt;80% for MGUS prevalence and comparison by HIV status. We performed protein electrophoresis with reflex immunofixation, as well as free light chain and creatinine quantification, and defined MGUS cases by the same criteria as the Olmsted County studies. If creatinine was greater than the upper limit of normal, then the renal reference range was used for free-light-chain ratios . Historical proportions and means were compared with z-tests and t-tests, respectively. To determine associations between categorical variables, odds ratios (OR) were calculated with logistic regressions or Fisher Exact tests. The study cohort (n=515) was 60% female (n=309) with a median age of 50 years (range 35-80); 199 (38.6%) were HIV-positive, of whom 82.4% (n=164) were on ART, and 8.5% (n=17) had a CD4+ cell count of &amp;lt;200 cells/ul. These numbers reflected the overall national estimates (Kingdom of Eswatini, SHIMS2 Final Report, 2019). The MGUS prevalence (including LC-MGUS) standardized for age and sex was 13.2% (95%CI: 10.5-16.5) (n=68), which was significantly greater than Olmsted County (RR 3.1, p&amp;lt;0.0001). Most (84%, n=57) MGUS cases were LC. Prevalence of non-light-chain (NLC) MGUS was 2.1% (n=11), which was similar to Olmsted County. Of the 11 participants with NLC MGUS, 4 were considered very low risk for progression to malignancy, 6 low risk, 1 intermediate risk, and 0 high risk by Mayo stratification (Rajkumar, et al., Blood, 2005). HIV status was not found to be significantly associated with MGUS (OR: 1.05, 95%CI: 0.62-1.77). However, within the HIV-positive cohort, the odds of MGUS were 69% lower among those on ART (OR: 0.31, 95%CI: 0.11-0.82) when adjusted for age, sex, and wealth quintile. Furthermore, MGUS was 2.8 times more frequent in those with untreated HIV when compared to those with treated HIV (95%CI: 1.1-7.2, p=0.031), and 2.3 times more frequent when compared to non-HIV (95%CI: 1.0-5.6, p=0.056); treated HIV was not significantly different from non-HIV (data not shown). In conclusion, the MGUS prevalence in Eswatini was more than three-fold higher than that in Olmsted County, largely due to those with LC-MGUS. The high rate of HIV in Eswatini did not explain the high prevalence of MGUS, as the majority of those with HIV were on ART and only untreated HIV was significantly associated with MGUS.

Increased Risk of Monoclonal Gammopathy of Undetermined Significance in US Military Service Members: A Case-Control Study of 1,068 Service Members Deployed to Either Europe or Iraq, with or without Reported Burn Pit and Toxic Smoke Exposure

Background:Monoclonal Gammopathy of Undetermined Significance (MGUS) is a plasma cell disorder which may lead to and in all cases precedes multiple myeloma (MM). Although, the etiology of MGUS is unknown, multiple studies have shown an association between MGUS and pesticide exposure (Kachuri et al, Int. J. Cancer 2013). Furthermore, soldiers and First Responders may be at higher risk of developing MGUS as evidenced by a 2.4-fold increased risk for MGUS in Vietnam Veterans exposed to Agent Orange (Landgren et al, JAMA Oncol. 2015) and a 1.8-fold higher risk in World Trade Center (9/11 attacks)-exposed fire fighters compared to reference populations (Landgren et al, JAMA Oncol. 2018). US Service Members deployed to the Southwest Asia theater of military operations (e.g., Iraq and Afghanistan) may have been exposed to various airborne hazards including smoke and fumes from open burn pits (chemical, paint, munitions, petroleum, plastic, rubber, medical, human, and food waste), oil well fires, and aircraft fuel/exhaust. Researchers are currently investigating the long-term consequences from these exposures. We were motivated to determine whether US Service Members deployed to Iraq were at increased risk of developing MGUS. Methods: Serum samples and clinical data (N=1,068) were attained from the Armed Forces Health Surveillance Division (AFHSD), the central epidemiologic health registry and biorepository for the US Military after IRB exemptions were granted. A total of 534 US Service Members who deployed to Iraq between January 1, 2005 and June 30, 2007 and reported burn pit exposure, smoke, burning trash, etc. on their post-deployment health assessment form (exposed cases) were matched 1:1 to 534 Members deployed to Germany (matched controls) who were never deployed to Southwest Asia and denied toxic exposure. All cases were deployed ≥ 6 months, were ≥ 35 years old at time of deployment, remained in the military ≥ 10 years and had serum available in the AFHSD repository 10 years after deployment. Matched criteria included deployment year (+/- 10 years), age (+/- 3 years), sex, service branch, military rank, and occupation category. The 10-year post-deployment samples underwent laboratory testing to screen for monoclonal protein by immunofixation (IFE) using pentavalent antisera with positive samples confirmed and typed using IFE gels (Sebia) and for serum free light chains (sFLC; Sebia) performed on the DYNEX Agility platform. IFE-positive samples underwent serum protein electrophoresis (SPEP) quantification by capillary electrophoresis (Sebia). Results:The median age of exposed Service Members was 37 years (range: 35-52) and 37 years (range: 35-55) for controls (Table 1). In both cohorts, the frequency of White (64.8%), Black (18.7%), Hispanic (7.5%), and male (89%) patients were the same as was the distribution of military occupation, rank, and service branch. The median number of days deployed for exposed vs controls was 243 and 852, respectively. There was no statistically significant difference between burn pit exposed and controls in the combined prevalence of MGUS (IFE+ monoclonal protein) and light chain (LC) MGUS (abnormal sFLC ratio), 6.7% (95% Confidence Interval (CI): 4.8-9.2%) vs 5.4% (95% CI: 3.7-7.7%), respectively (p=0.22). Similarly, there was no difference in prevalence when assessing IFE+ or sFLC+ cases separately (Table 2). The prevalence of MGUS or LC-MGUS for all 1,068 Service Members was 6.1% (95% CI: 4.7-7.7%). Conclusion:In our cohort of 534 Service Members deployed to Iraq and exposed to burn pits and other airborne toxic hazards (cases) there was no statistically significant difference in the prevalence of MGUS compared to 534 deployed to Germany (matched controls). Interestingly, the overall prevalence of MGUS/LC-MGUS in this combined deployed population was 6.1%. When taking into account that the median age at deployment was 37 years and samples were attained 10 years later (approximately at an age of 47 years), the observed prevalence is 3-fold higher than that reported in the Icelandic iStopMM study (2% in the 41-50 -year age group). Future studies are needed to further elucidate causes for the increased prevalence of MGUS/LC-MGUS in deployed US Military Service Members. This contents is the sole responsibility of the authors and do not necessarily reflect the views, opinions or policies of the US Government nor endorsement of commercial products mentioned.

The China Monoclonal Gammopathy Screening Project in First-Degree Relatives of Patients with Multiple Myeloma (CHAPERONE) –a Multicenter Screening Study

Background and Significance: Multiple myeloma (MM) evolves from the precursor state monoclonal gammopathy of undetermined significance (MGUS). According to previous reports, the incidence of MM and its precancerous state MGUS was lower in Asian populations than in Western populations. However, with the aging of the population, we found that the incidence of MM in China has been on the rise in recent years, and the medical burden has continued to increase. Therefore, early recognition of MM and its precursor condition is even more critical. Our previous research has confirmed that monoclonal gammopathy (M-protein) screening and close follow-up of MGUS can increase the early diagnosis rate of MM and improve the prognosis of MM patients[1]. M-protein screening in healthy people at high risk for MM is a rational strategy. The risk of MM in the first-degree relatives of myeloma patients is 2-4 times that of the general population, constituting a high-risk group for MM. Although the screening of M-protein in high-risk populations has been explored in the US (the PROMISE study), little was known about the incidence, clinical features, and prognosis of MGUS in high-risk groups in China. Here, we describe the first prospective screening project to assess the potential benefits of M-protein screening and the prevalence and outcomes of MGUS in first-degree relatives of patients with multiple myeloma in the China population (NCT05965115). Study Design and Methods: The CHAPERONE study is a prospective, multicenter screening study for MGUS in first-degree relatives of MM patients, including a risk-stratified follow-up strategy(Figure). Clinical trial registry number: NCT05965115, actively recruiting. This study aims to assess the clinical significance of screening for monoclonal gammopathy in first-degree relatives of patients with multiple myeloma in China. The primary objective is to determine the prevalence and incidence rate of MGUS, the time to disease progression (TTP), and its influencing factors in first-degree relatives of MM patients in China. The secondary and exploratory study objective is to explore the clinical/genomic features, survival, and quality of life of the screened MGUS cases. The expected screening size is 10,000 healthy persons. To be eligible, participants must be over 18, with one or more first-degree relatives (including parents, children, and biological siblings) having multiple myeloma diagnosed by the International Myeloma Working Group (IMWG) Myeloma Diagnostic Criteria. Participants with a known diagnosis of plasma cell diseases, such as MGUS, smoldering myeloma (SMM), or MM, will be excluded. All eligible participants will receive M-protein screening by serum electrophoresis. Individuals with detected M-protein will undergo further diagnostic tests, including peripheral blood tests (immunofixation electrophoresis, serum free light chain, immunoglobulin quantification, blood routine, liver and kidney function, and blood calcium level) and X-ray bone assays. Patients with suspecting MM features will undergo further bone marrow surveys to ascertain the diagnosis. Patients with MGUS will be carefully assessed and stratified by the risk of progression to MM according to the IMWG MGUS consensus. Low-risk MGUS will be followed-up annually, while intermediate/high-risk MGUS will be biannual. Participants who progress to MM will be offered early treatment. Conclusions and Future Directions: One path to making MM a preventable cancer is better understanding its precursor condition (MGUS). This trial is positioned to provide epidemiology, clinical, and potential mechanistic data on MGUS at a high-risk group in China population that has yet to be thoroughly studied. Reference: [1] Li J, Wang Y, Liu P. The impact on early diagnosis and survival outcome of M-protein screening-driven diagnostic approach to multiple myeloma in China: a cohort study[J]. J Cancer, 2019, 10(20): 4807-4813.

Geographic Prevalence Patterns and Modifiable Risk Factors for Monoclonal Gammopathy of Undetermined Significance

Monoclonal gammopathy of undetermined significance (MGUS) is a pre-malignant plasma cell disorder with an etiology that is incompletely understood. Modifiable risk factors and genetic predispositions likely interact to increase MGUS risk in specific individuals and populations. Identifying geographic prevalence patterns and modifiable risk factors is critical for understanding the etiology of MGUS. The aim of this review was to outline original research on MGUS prevalence across geographic locations and modifiable risk factors. We conducted a systematic review of 39 eligible studies from PubMed®, Embase®, and Web of Science® written in English and published by February 2023. Our protocol was registered in accordance with PROSPERO guidelines. Studies were synthesized using Research Electronic Data Capture and appraised using the National Heart, Lung, and Blood Institute study quality assessment tools. The prevalence of MGUS ranged from 0.24% to 9% across geographic locations. Modifiable risk factors for MGUS include infections, autoimmune diseases, chronic inflammatory conditions, lifestyle factors, environmental exposures, and ionizing radiation. Therefore, the development of MGUS may be related to chronic antigenic stimulation and genetic aberrations that promote clonal proliferation of plasma cells. Prospective studies assessing gene–environment interactions are needed to further define risk factors for MGUS and inform screening and preventative strategies.

Vitamin D and monoclonal gammopathy of undetermined significance (MGUS) among U.S. Black women.

Risk factors for monoclonal gammopathy of undetermined significance (MGUS), the asymptomatic precursor to multiple myeloma, are largely unknown. We hypothesized that low vitamin D levels might be associated with higher MGUS prevalence in a national cohort of U.S. Black women. We screened archived serum samples (collected 2014-2017) from 3896 randomly selected participants in the Black Women's Health Study ages 50-79 for evidence of MGUS; samples had been assayed for 25-hydroxyvitamin D [25(OH)D] shortly after blood draw. We used logistic regression to estimate odds ratios (OR) and 95% confidence intervals (CI) for the association between 25(OH)D level and MGUS status, adjusting for age, body mass index, and season of blood draw. We identified 334 MGUS cases (8.6%) in the study population. The adjusted OR comparing women with vitamin D deficiency (25(OH)D < 20 ng/mL) to those with 25(OH)D levels ≥ 30 ng/mL was 1.27 (95% CI: 0.95, 1.72). MGUS was more prevalent among Black women with vitamin D deficiency compared to those with 25(OH)D ≥ 30 ng/mL; however, the association was not statistically significant. Future prospective studies are warranted to clarify the possible association between vitamin D and MGUS.

Abstract 6480: Mortality in patients with monoclonal gammopathy of undetermined significance: an analysis of National Health and Nutrition Examination Survey

Abstract Introduction: Monoclonal gammopathy of undetermined significance (MGUS) is an asymptomatic premalignant plasma cell disorder with an annual risk of ~1% of progression to more advanced diseases, including multiple myeloma (MM). Few studies reported mortality risk in patients with MGUS, among which the diagnosis of MGUS was typically incidental due to unrelated symptoms or laboratory abnormalities. This study aims to compare the survival of MGUS patients with the U.S. general population using a nationally representative screening-based survey. Methods: Data were obtained from the third National Health and Nutrition Examination Survey (NHANES III) 1988-1994 and continuous NHANES 1999-2004, with follow-up all-cause mortality data through December 31, 2019. Participants were screened for MGUS by protein electrophoresis, immunofixation, and kappa and lambda free light chain assays in serum. Multivariable Cox-proportional regressions were performed, adjusting for demographic characteristics (age, gender, race/ethnicity, education, income, body mass index [BMI]), health behaviors (smoking, physical activity), baseline medical conditions (hypertension, diabetes, osteoporosis, myocardial infarction, stroke, congestive heart failure, coronary heart disease, peripheral vascular disease [PVD], arthritis, liver diseases, chronic obstructive pulmonary disease, renal diseases, cancer), and survey year. We also tested the interaction between race/ethnicity and MGUS diagnosis in the fully adjusted model. The NHANES complex sampling design was accounted for in all analyses to obtain population estimates. Results: The prevalence of MGUS among the U.S. population aged 50 years or older was 2.5% in 1988-1994 (sample size n=6,557; population size N=56,136,480) and 2.3% in 1999-2004 (n=5,847; N=68,835,295). MGUS patients were older and more likely to have PVD (13.1% vs. 7.7%, p = 0.03). No evidence was found showing a difference in gender distribution, education, income, BMI, and other comorbidities between the two populations. In NHANES 1999-2004, MGUS was associated with an increased risk of death (Hazard ratios [HR] 1.20, 95% CI: 1.02-1.41, p = 0.03) compared to the general population. NHANES III also showed a trend toward increased risk of mortality (HR 1.15, 95% CI: 0.89-1.48, p = 0.27). No interaction between race/ethnicity and MGUS diagnosis was found. It was notable that PVD was associated with an increased risk of death (HR 1.67, 95% CI: 1.43-1.94, p &amp;lt; 0.001). Conclusion: In the large cohort of NHANES participants, MGUS was associated with an increased risk of mortality. MGUS is typically viewed as a “benign” condition that has the potential to progress to cancer. These findings suggest that there may be alternate health implications to a diagnosis of MGUS. Future studies should focus on the causes of death in this population and the role of MGUS. Citation Format: Mengmeng Ji, John Huber, Mei Wang, Yi-Hsuan Shih, Yao-Chi Yu, Lawrence Liu, Theodore Thomas, Martin W. Schoen, Kristen M. Sanfilippo, Graham A. Colditz, Shi-Yi Wang, Su-Hsin Chang. Mortality in patients with monoclonal gammopathy of undetermined significance: an analysis of National Health and Nutrition Examination Survey [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 6480.

Abstract C013: Racial difference in risk factors for monoclonal gammopathy of undetermined significance – The premalignant stage of multiple myeloma

Abstract Background: Black race and obesity are known risk factors for type 2 diabetes mellitus (T2DM), multiple myeloma and its precursor condition – monoclonal gammopathy of undetermined significance (MGUS). Yet, little is known about what contributes to this racial difference, particularly in MGUS, and studies have inconsistently shown that T2DM may not be a risk factor for myeloma. We aimed to investigate the racial differences in risk factors for MGUS in patients with T2DM. Methods: Patients diagnosed with T2DM from 1999-2021 in the Veterans Health Administration were identified. We used a natural language processing-based algorithm to confirm MGUS diagnosis. Among them, patients of Black and White races with ≥2 BMI measurements were included. To preserve the prevalence of MGUS in the respective population, each Black patient with MGUS was matched to 27 Black patients without MGUS; and each White patient with MGUS was matched to 44 White patients without MGUS on BMI observation window. BMI observation window for each MGUS patient was defined as time from the 1st to the last BMI measurement before MGUS diagnosis. For the matched patients without MGUS, a similar length of observation window was selected along with ≥1 measurement beyond the window to ensure no loss to follow-up during the window. Each cohort was further split into the training (80%) and testing (20%) sets. Ad-hoc features for BMI in different statistics to summarize repeated measurements within the window were defined: average, variance (var), maximum (max), minimum (min), max BMI increase per month (max dBMI/m), max BMI decrease per month (min dBMI/m), and area under the dBMI curve. Ad-hoc features for other variables, HbA1c, creatinine, potassium, and glucose, were constructed in a similar fashion. To overcome the imbalanced MGUS cases (vs no MGUS), Synthetic Minority Over-Sampling Technique algorithm was used. To evaluate performance, we implemented 5-fold cross-validation using logistic regression and generated AUC score. Results: A total of 2,468 White and 3,981 Black T2DM MGUS patients were included. Logistic regression achieved an average AUC score of 0.76 (95% CI 0.72, 0.79) for Whites and 0.76 (95% CI 0.73, 0.78) for Blacks. In both races, the most significant risk factor for MGUS was max dBMI/m, followed by max BMI for Whites and var BMI for Blacks. Conversely, min glucose was the most significant factor inversely associated with the incidence of MGUS for both races. Conclusion: There is no significant difference in the most significant factors contributing to MGUS between the two races. In patients with T2DM, drastic change in body weight is the most significant risk factor for MGUS among others, while maintaining low glucose is the most protective factor for both races. Regardless of race, T2DM patients of high myeloma risk are encouraged to maintain a stable weight and low glucose level. Citation Format: Yao-Chi Yu, Mei Wang, Akhil Kumar, Kristin Vargo, Lawrence Liu, Theodore Thomas, Kristen Sanfilippo, Martin Schoen, Graham Colditz, Jr-Shin Li, Su-Hsin Chang. Racial difference in risk factors for monoclonal gammopathy of undetermined significance – The premalignant stage of multiple myeloma [abstract]. In: Proceedings of the 15th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2022 Sep 16-19; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr C013.

Association of Pulmonary Hypertension and Monoclonal Gammopathy of Undetermined Significance.

To determine the prevalence of monoclonal gammopathy of undetermined significance (MGUS) in patients with PH as well as precapillary PH. Olmsted County residents with PH, diagnosed between 1/1/1995 and 9/30/2017, were identified, and age and sex were matched to a normal control group. The PH group and normal control group were then cross-referenced with the Mayo Clinic MGUS database. Charts were reviewed to verify MGUS and PH. Heart catheterization data were then analyzed in these patients for reference to the gold standard for diagnosis. There were 3419 patients diagnosed with PH by echocardiography between 1995 and 2017 in Olmsted County that met the criteria of our study. When the PH group (N = 3313) was matched to a normal control group (3313), a diagnosis of MGUS was significantly associated with PH 10.2% (OR = l.84 [95% CI 1.5-2.2], p < 0.001), compared with controls 5.8% based on echo diagnosis. Using heart catheterization data (484 patients), a diagnosis of MGUS was associated with PH 13.0% (OR = 3.94 [95% CI 2.28-6.82], p < 0.001). For pulmonary artery hypertension (N = 222), a diagnosis of MGUS was associated with PH at similar 12.2% (OR = 4.50 [95%CI 1.86-10.90], p < 0.001. There is a higher prevalence of MGUS in patients with PH and precapillary PH compared with normal controls. This association cannot be explained fully by other underlying diagnoses associated with PH. Assessing for this in patients with PH of unclear etiology may be reasonable in the workup of patients found to have PH.

Prevalence of MGUS Is High in the Istopmm Study but the Prevalence of IgA MGUS Does Not Increase with Age in the Way Other Immunoglobulin Subtypes Do

Introduction: Monoclonal gammopathy of undetermined significance (MGUS) is an asymptomatic plasma cell disorder that precedes the onset of multiple myeloma (MM) and other lymphoproliferative disorders. Detailed data on the prevalence and natural course of MGUS are key to understanding the risk of MGUS progression, as well as providing relevant clinical advice to individuals with MGUS on their personal risk and optimal follow-up strategy. Data on the prevalence of MGUS in the general population collected at the end of the 20th century have served as the key reference for physicians and researchers seeking to understand the epidemiology of MGUS in the general population. Nearly a quarter century later we are now able to use data from the Iceland Screens, Treats, or Prevents Multiple Myeloma (iStopMM) study to refine our understanding of MGUS further and provide a more detailed picture of the prevalence and characteristics of MGUS in a screened population. Aims: Describe the population prevalence of MGUS by age and sex, the prevalence of individual immunoglobulin subtypes, and the distribution of risk groups. Methods: The iStopMM study has screened 75,422 individuals, representing 51% of all Icelanders aged 40 and over at the time of study initiation. To detect and quantify monoclonal proteins, serum protein electrophoresis (SPEP) was performed on all samples followed by immunofixation electrophoresis (IFE) if a monoclonal spike was found or if the free light chain (FLC) ratio was abnormal. Age was based on the date of sample collection. We used these data to calculate the population prevalence of MGUS, age- and sex- standardized to the invited study population of all 148,704 individuals aged 40 and over living in Iceland at the start of the study. We calculated separate prevalence rates for the whole study group and for individuals over 50 to allow for direct comparison to prior studies. Then we plotted the prevalence in 10-year age groups by sex with 95% confidence intervals (CI). In a second graph we used 5-year age groups and plotted the prevalence of MGUS as well as of each of three subtypes of immunoglobulins, IgG, IgM, and IgA and multiclonal MGUS. Age groups over 85 were collapsed into one. We added cubic smoothing splines with bootstrapped 95% confidence intervals (CI) to both plots. Finally, we used the Mayo Clinic risk stratification model to assign all individuals diagnosed with MGUS to risk groups. Results: In 75,422 screened samples we diagnosed MGUS in 3,358, with IgG in 1,923 (57%), IgM in 721 (21%), IgA in 400 (12%), and more than one clonal spike in 314 (9%). The crude prevalence of MGUS in the study group was 4.5% (95% CI 4.3%-4.6%). The age and sex standardized prevalence was 3.9% (95% CI 3.8%-4.0%) for the whole group, and 5.0% (95% CI 4.9%-5.2%) when limited to age over 50. The crude prevalence rates with 95% CIs are shown for 10-year age groups divided by sex in Figure 1. Figure 2 shows the crude prevalence rates by 5-year age groups for MGUS and subtypes of immunoglobulin monoclonal spikes. Based on the Mayo Clinic risk stratification model, 1,445 (43.0%) were low risk, 1,356 (40.4%) were low-intermediate risk, 547 (16.3%) were high-intermediate risk, and 10 (0.30%) were at high risk for progression. Discussion: The results presented here show an age- and sex- standardized prevalence of 5% among individuals over 50 years of age in the largest population-based screening study of MGUS among individuals of Western European descent to date. This is a higher population standardized prevalence of MGUS than previously reported for this age group, but this study confirms the pattern of higher prevalence with increasing age and male gender seen in other studies. Our data show, for the first time, that IgA MGUS behaves in sharp contrast to other immunoglobulin subtypes, with prevalence rising slowly with advancing age, if at all after age 70. As previous studies show that immunosenescence involves an increased amount of overall IgA secretion, a phenomenon also observed in the iStopMM study (data not shown), it is important to consider several potential explanations, including that IgA M-proteins are more often transient, arise less frequently later in life, or are associated with a shortened lifespan. Follow-up data from the iStopMM study will provide further insights into this new discovery. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Prevalence of Monoclonal Gammopathies Detected By Mass Spectrometry and Their Risk Factors Among Black Africans in South Africa

Background Monoclonal gammopathy of undetermined significance (MGUS) is a premalignant expansion of plasma cells that always precedes the development of multiple myeloma. Recent U.S.-based screening studies utilizing matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) mass spectrometry (MS) reported a high prevalence of monoclonal gammopathies (MGs) among Blacks. One study observed among Blacks over age 50 years, a high prevalence of MGUS (17%) as well as low-level MGs below the detection threshold of serum protein electrophoresis/immunofixation (SPEP/IFX) assays, termed monoclonal gammopathy of indeterminate potential (MGIP, 31% prevalence). In the current study, we aimed to define the prevalence of MGs by MALDI-TOF MS in a Black population in South Africa and evaluate its association with risk factors (e.g., obesity). Methods Individuals who self-identify as Black African and aged >=40 years were recruited from Soweto, Johannesburg, South Africa to participate in the study. Those with a prior diagnosis of a plasma cell dyscrasia and/or any cancer history requiring active therapy were excluded. Serum samples of participants were analyzed using the Binding Site Group's EXENT® assay based on MALDI-TOF MS for the quantification of M-proteins. M-proteins >=0.2 g/L were categorized as MGUS, and those <0.2 g/L were MGIP. This concentration threshold of 0.2 g/L was the lower detection limit of SPEP/IFX-determined by serial dilution sensitivity testing comparing MALDI-TOF MS and SPEP/IFX assays, performed and provided by the manufacturer and reported in a prior study. Participants’ heights and weights were measured at enrollment and used to calculate body mass index (BMI, kg/m2). All participants completed a survey querying sociodemographic factors, clinician-diagnosed comorbidities, and lifestyle factors. Logistic regression models estimated odds ratios (OR) and 95% confidence intervals (CI) for exposure and MGUS/MGIP associations. Results As of June 2022, 738 participants enrolled in the study. Median age was 52 years (range, 40-79), and 52% were female. 3% reported an educational status of college graduate or above. Ethnic background of participants included 38% IsiZulu, 20% Sesotho, 13% IsiXhosa, 13% Setswana, 5% Tsonga, 4% Sepedi, 4% Seswati, and 1% Tshivenda. The prevalence of MGUS and MGIP was 12% and 17% in the entire cohort and 13% and 18% in those aged >=50 years. MGUS was predominantly IgG (89%), followed by IgA (7%) and IgM (4%). MGIP was predominantly IgM (81%), followed by IgA (15%) and IgG (4%). In univariate analysis, MGs were associated with increasing 10-year age intervals (OR, 1.40; 95% CI, 1.17-1.67). Mean BMI was 27 kg/m2, and 27% of participants were obese (>=30 kg/m2). Adjusting for age, sex, and education, obesity was associated with all MGs (OR, 1.49; 95% CI, 1.01-2.20). Obesity was associated with MGIP (OR, 1.94; 95% CI, 1.20-3.12) and not with MGUS (OR, 1.04; 95% CI, 0.58-1.82). Diabetes was also associated with MGIP (OR, 2.98; 95% CI, 1.19-7.19). HIV was reported in 23% of participants, among whom 99% reported current HIV treatment. HIV was not associated with MGUS or MGIP. All other comorbidities, including cardiovascular disease, stroke, COPD/emphysema, arthritis, liver disease, and chronic kidney disease, were reported in <=1% of participants. As for lifestyle factors, heavy alcohol consumption (>=30 g/day) was associated with MGUS (OR, 2.76; 95% CI, 1.47-5.51). Heavy smoking (>10 pack-years) had a trend toward association with MGUS (OR, 1.81; 95% CI, 0.98-3.32). Short sleep (<=6 hours/day) was associated with MGIP (OR, 2.11; 95% CI, 1.22-3.59). Conclusion These results are the first to describe a high prevalence of MGUS detected by MS (13%) for a Black African cohort aged >=50 years, consistent with high prevalence estimates of MS-detected MGUS recently reported in U.S. Blacks. Obesity and diabetes were associated with MGIP, an entity that currently bears unknown etiology. We, however, did not observe associations for obesity and related comorbidities with MGUS, possibly due to limited sample size. Nonetheless, these first results along with other observed novel risk factor associations (e.g., MGUS and heavy alcohol consumption) in our expanding South African cohort provide clues to pathophysiological mechanisms of MGs and may inform interception strategies in preventing their progression.

Persistence of Monoclonal Gammopathies in Serial Samples from a US Population-Based Screening Study

Background: The prevalence of monoclonal gammopathy of undetermined significance (MGUS) in a population at high risk of developing multiple myeloma (MM) was recently described in a US screening study. In a high-risk population, MGUS prevalence was measured as 6% by serum protein electrophoresis with immunofixation (SPEP/IFX) and 13% by matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS). Screening by MALDI-TOF MS allowed for the detection of monoclonal proteins (M-proteins) below the threshold of detection of gel-based assays, that was referred to as Monoclonal Gammopathy of Indeterminate Potential (MGIP). MGIP was found in 25% of the screened cohort and was significantly associated with aging. Other studies indicated that MGUS and MGIP detected by MS may be transient and their detection may not be critical for long term outcomes. Therefore, we aimed to determine the fate of M-proteins detected by MS in a US population-based study. Methods: High-risk individuals enrolled in the study include those who self-identify as Black or have a family history of hematologic malignancies or a precursor condition to MM. Samples that tested positive for MGUS (M-protein >= 0.2 g/L) by MALDI-TOF MS were confirmed using clinically approved assays and results were returned to participants. All participants who had an M-protein detected at baseline by MALDI-TOF MS were invited to submit follow-up samples to investigate the fate of the M-proteins detected at the MGIP and MGUS levels. Serum was analyzed using the Binding Site Group's EXENT® assay based on MALDI-TOF MS for the identification and quantification of M-proteins. Persistence of the M-protein detected at baseline was defined as the presence of the same isotype M-protein on a serial sample and within +/-5 mass to charge ratio on mass spectra. All serial samples where the M-protein was not detected by MALDI-TOF MS were reflex tested to liquid chromatography (LC) MS. Results: We analyzed 262 multi-timepoint samples collected from 102 participants who tested positive for an M-protein, with a median follow-up of 336 days (Range 36 - 1,240; IQR 141 - 737). The median age at screening was 60.8 years, 65 (64%) participants were female, 9 (9%) self-identified as Black, and 93 (91%) were non-Black and reported a family history of hematologic malignancy. At baseline, 66 (65%) participants had MGIP (M-protein <0.2g/L) and 36 (35%) had MGUS (M-protein >=0.2/L) measured by MALDI-TOF MS. All participants with MGIP were negative at baseline by SPEP/IFX, while among those with MGUS at baseline, 25/36 (69%) participants had an M-protein detected by SPEP/IFX. At baseline, the distribution of isotypes was 21% IgG, 17% IgA, and 62% IgM for MGIP and 69% IgG, 17% IgA, and 14% IgM for MGUS. For all 102 cases, their most recent serial samples were tested by MALDI-TOF MS or LC-MS. 60/66 (91%) of the MGIP cases were re-confirmed on serial sampling, with a median follow-up time of 504 days (Range 41 - 1,240; IQR 149 - 888). As for MGUS, 36/36 (100%) of cases detected at baseline persisted on serial sampling, with a median follow-up time of 239 days (Range 36 - 1105; IQR 103 - 628) (Figure 1). Time from baseline to serial sampling was not associated with persistence. In 12 participants so far, M-proteins detected by MS were seen to persist for more than 3 years after baseline testing. In 5 of the MGIP cases, M-protein concentration measured by MALDI-TOF MS increased from MGIP level to above the MGUS threshold. These participants had a median baseline M-protein concentration of 0.14 g/L (Range 0.13 - 0.17 g/L; IQR 0.13 - 0.14), which was in the upper MGIP concentration level, and had a median follow-up time of 532 days (Range 171 - 1,127; IQR 302 - 570). Of these, 3 persisted as IgG, 1 IgA, and 1 IgM isotypes. Conclusion: We present the first longitudinal analysis of M-proteins detected by MS, including those below the threshold of detection of gel-based assays, in a US population-based screening study. Results confirm the persistence of 91% of MGIP and 100% of MGUS cases detected by MS. Some cases showed increasing M-protein concentration, crossing the threshold of detection by gel-based assays. Additional studies are underway to further validate our findings in a larger cohort with longer follow-up time. Testing serial samples with increasing M-protein concentration by gel-based assays will help better understand the significance of early detection of MGIP cases by MS. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Prevalence of Monoclonal Gammopathy of Undetermined Significance in Black South African Men.

Both multiple myeloma and its precursor, monoclonal gammopathy of undetermined significance (MGUS), occur twice as often within Black compared with White populations, suggesting that racial disparities lie within the development of MGUS. Nonetheless, MGUS has been studied mainly in White cohorts; the study that first described the natural history of MGUS was conducted in 97.3% White Olmsted County, Minnesota. We determined the prevalence of MGUS among 386 Black South African (SA) men >30 years at Chris Hani Baragwanath Hospital in Johannesburg. We conducted serum protein electrophoresis and free light chain quantification to define MGUS by the same criteria as the Olmsted County studies. We also investigated the association between MGUS and various clinical factors, including human immunodeficiency virus (HIV) infection and smoking. We found the prevalence of MGUS to be 8.03% [95% confidence interval (CI), 5.32-10.74], nearly 1.6-fold higher than in the White Olmsted County male population. In a univariable logistic regression model, MGUS was associated with HIV status (OR, 2.39; 95% CI, 0.95-5.49), but in an adjusted model that included body mass index and cigarette use, the association was not statistically significant. Those who were current (vs. never) cigarette smokers were more likely to have MGUS in both univariable (OR, 5.60; 95% CI, 2.16-17.42) and multivariable models (OR, 4.49; 95% CI, 1.63-14.56). The prevalence of MGUS in Black SA men is substantially higher than in White populations and may be associated with HIV status and cigarette use. Racial disparities in MGUS exist and may be associated with potentially modifiable risk factors.

Myeloma precursor disease (MGUS) among rescue and recovery workers exposed to the World Trade Center disaster

An elevated risk of myeloma precursor disease, monoclonal gammopathy of undetermined significance (MGUS), was identified among Fire Department of the City of New York (FDNY) World Trade Center (WTC)-exposed firefighters. Further investigation was needed to determine if these findings were reproducible in a more heterogeneous WTC-exposed rescue/recovery workers cohort, the Stony Brook University-General Responder Cohort GRC (SBU-GRC). MGUS risk was compared between the cohorts and to published general population estimates from Olmsted County, MN, USA. In this observational seroprevalence study, odds ratios (OR) and age-standardized risk ratios (RR) of MGUS (M-spike and light-chain-MGUS combined), M-spike, and light-chain-MGUS were estimated using logistic regression. Age-standardized prevalences were calculated for white males aged 50–79; RRs were estimated by comparing risk in the WTC-exposed cohort with the Olmsted County screened cohort. SBU-GRC had elevated odds of MGUS compared with FDNY (OR = 1.38; 95%CI = 1.00–1.89). The age-standardized prevalence of MGUS was 9.0/100 persons (95%CI = 7.5–10.6), over two-fold higher than the general population (RR = 2.08; 95%CI = 1.72–2.51); the age-standardized prevalence of light-chain-MGUS was 3.5-fold higher (RR = 3.54; 95%CI = 2.52–4.97). This study adds to mounting evidence supporting an association between WTC/environmental exposures and MGUS among rescue/recovery workers. Access to MGUS screenings for the entire WTC-exposed cohort could allow for treatment interventions that improve survival.