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3216 Prevalence of Monoclonal Gammopathies Detected By Mass Spectrometry and Their Risk Factors Among Black Africans in South Africa

Program: Oral and Poster Abstracts
Session: 652. Multiple Myeloma and Plasma Cell Dyscrasias: Clinical and Epidemiological: Poster II
Hematology Disease Topics & Pathways:
Research, adult, epidemiology, Clinical Research, Plasma Cell Disorders, Diseases, Lymphoid Malignancies, Study Population, Human
Sunday, December 11, 2022, 6:00 PM-8:00 PM

David J. Lee, MD1,2,3,4, Habib El-Khoury, MD3,5, Luca Bertamini, MD3,5*, Jean-Baptiste Alberge, PhD3,4,5*, Maya I. Davis, BA3,5*, Jacqueline Perry, MPH3,5*, Dhananjay Sakrikar, PhD6*, David Barnidge, PhD6*, Mark C. Perkins, PhD7*, Stephen Harding, PhD7, Derek Troske, BS6*, Audrey Pentz, B.Rad(T)8*, Thulisile Hlubi8*, Natalie Smyth, MS9*, Anna Cowan, BA10*, Angela C. Tramontano, MPH5*, Gad Getz, PhD3,4,11,12*, Timothy R. Rebbeck, PhD5,13*, Maureen Joffe, PhD8*, Wenlong Carl Chen, PhD8,14,15*, Catherine R. Marinac, PhD3,5,16 and Irene Ghobrial, MD3,5,16

1Department of Medicine, Massachusetts General Hospital, Boston, MA
2Department of Medical Oncology, Dana-Farber Cancer Institute, Cambridge, MA
3Harvard Medical School, Boston, MA
4Broad Institute of MIT and Harvard, Cambridge, MA
5Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA
6The Binding Site Inc., Rochester, MN
7The Binding Site Inc., Birmingham, United Kingdom
8Noncommunicable Diseases Research Division, Wits Health Consortium (PTY) Ltd, Johannesburg, South Africa
9Sydney Brenner Institute for Molecular Bioscience, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa
10Alix School of Medicine, The Mayo Clinic, Rochester, MN
11Center for Cancer Research, Massachusetts General Hospital, Boston, MA
12Department of Pathology, Massachusetts General Hospital Cancer Center, Boston, MA
13Harvard T.H. Chan School of Public Health, Boston, MA
14Faculty of Health Sciences, University of the Witwatersrand, Sydney Brenner Institute for Molecular Bioscience, Johannesburg, South Africa
15National Health Laboratory Service, National Cancer Registry, Johannesburg, South Africa
16The Center for Prevention of Progression of Blood Cancers, Dana-Farber Cancer Institute, Boston, MA


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).


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.


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).


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.

Disclosures: Sakrikar: The Binding Site Group Ltd: Current Employment. Barnidge: The Binding Site Group Ltd: Current Employment. Perkins: The Binding Site Group Ltd: Current Employment. Harding: The Binding Site: Current Employment, Membership on an entity's Board of Directors or advisory committees. Troske: The Binding Site Group Ltd: Current Employment. Getz: IBM: Research Funding; MSMuTect: Patents & Royalties; Scorpion Therapeutics: Consultancy, Current equity holder in publicly-traded company, Other: Founder; MSMutSig: Patents & Royalties; MSIDetect: Patents & Royalties; SignatureAnalyzer-GPU: Patents & Royalties; Pharmacyclics: Research Funding; POLYSOLVER: Patents & Royalties. Ghobrial: Veeva Systems: Honoraria; Pfizer: Honoraria; Janssen: Honoraria; Menarini Silicon Biosystems: Honoraria; The Binding Site: Honoraria; Takeda: Honoraria; Window Therapeutics: Other: Advisory board participation; Sanofi: Honoraria; Sognef: Honoraria; Oncopeptides: Honoraria; Huron Consulting: Honoraria; GSK: Honoraria; Bristol Myers Squibb: Honoraria; Aptitude Health: Honoraria; Vor Biopharma: Honoraria; Amgen: Honoraria; AbbVie: Honoraria; Adaptive: Honoraria; Novartis: Research Funding; Celgene: Research Funding.

*signifies non-member of ASH