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Lancet Haematol DOI:10.1016/S2352-3026(22)00069-2

Prevalence of monoclonal gammopathies and clinical outcomes in a high-risk US population screened by mass spectrometry: a multicentre cohort study.

Publication TypeJournal Article
Year of Publication2022
AuthorsEl-Khoury, H, Lee, DJ, Alberge, J-B, Redd, R, Cea-Curry, CJ, Perry, J, Barr, H, Murphy, C, Sakrikar, D, Barnidge, D, Bustoros, M, Leblebjian, H, Cowan, A, Davis, MI, Amstutz, J, Boehner, CJ, Lightbody, ED, Sklavenitis-Pistofidis, R, Perkins, MC, Harding, S, Mo, CC, Kapoor, P, Mikhael, J, Borrello, IM, Fonseca, R, Weiss, ST, Karlson, E, Trippa, L, Rebbeck, TR, Getz, G, Marinac, CR, Ghobrial, IM
JournalLancet Haematol
Date Published2022 Mar 25

BACKGROUND: Prevalence estimates for monoclonal gammopathy of undetermined significance (MGUS) are based on predominantly White study populations screened by serum protein electrophoresis supplemented with immunofixation electrophoresis. A prevalence of 3% is reported for MGUS in the general population of European ancestry aged 50 years or older. MGUS prevalence is two times higher in individuals of African descent or with a family history of conditions related to multiple myeloma. We aimed to evaluate the prevalence and clinical implications of monoclonal gammopathies in a high-risk US population screened by quantitative mass spectrometry.

METHODS: We used quantitative matrix-assisted laser desorption ionisation-time of flight (MALDI-TOF) mass spectrometry and EXENT-iQ software to screen for and quantify monoclonal gammopathies in serum from 7622 individuals who consented to the PROMISE screening study between Feb 26, 2019, and Nov 4, 2021, and the Mass General Brigham Biobank (MGBB) between July 28, 2010, and July 1, 2021. M-protein concentrations at the monoclonal gammopathy of indeterminate potential (MGIP) level were confirmed by liquid chromatography mass spectrometry testing. 6305 (83%; 2211 from PROMISE, 4094 from MGBB) of 7622 participants in the cohorts were at high risk for developing a monoclonal gammopathy on the basis of Black race or a family history of haematological malignancies and fell within the eligible high-risk age range (30 years or older for PROMISE cohort and 18 years or older for MGBB cohort); those over 18 years were also eligible if they had two or more family members with a blood cancer (PROMISE cohort). Participants with a plasma cell malignancy diagnosed before screening were excluded. Longitudinal clinical data were available for MGBB participants with a median follow-up time from serum sample screening of 4·5 years (IQR 2·4-6·7). The PROMISE study is registered with, NCT03689595.

FINDINGS: The median age at time of screening was 56·0 years (IQR 46·8-64·1). 5013 (66%) of 7622 participants were female, 2570 (34%) male, and 39 (

INTERPRETATION: We detected a high prevalence of monoclonal gammopathies, including age-associated MGIP, and made more precise estimates of mass-spectrometry MGUS compared with conventional gel-based methods. The use of mass spectrometry also highlighted the potential hidden clinical significance of MGIP. Our study suggests the association of monoclonal gammopathies with a variety of clinical phenotypes and decreased overall survival.

FUNDING: Stand Up To Cancer Dream Team, the Multiple Myeloma Research Foundation, and National Institutes of Health.


Alternate JournalLancet Haematol
PubMed ID35344689