Prevalence of monoclonal gammopathies and clinical outcomes in a high-risk US population screened by mass spectrometry: a multicentre cohort study.
| Title: | Prevalence of monoclonal gammopathies and clinical outcomes in a high-risk US population screened by mass spectrometry: a multicentre cohort study. |
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| Authors: | El-Khoury H; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA; Harvard Medical School, Boston, MA, USA.; Lee DJ; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA; Harvard Medical School, Boston, MA, USA; Department of Medicine, Massachusetts General Hospital, Boston, MA, USA.; Alberge JB; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA; Harvard Medical School, Boston, MA, USA; Broad Institute of MIT and Harvard, Cambridge, MA, USA.; Redd R; Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, MA, USA.; Cea-Curry CJ; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA; Harvard Medical School, Boston, MA, USA.; Perry J; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA; Harvard Medical School, Boston, MA, USA.; Barr H; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA; Harvard Medical School, Boston, MA, USA.; Murphy C; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA; Harvard Medical School, Boston, MA, USA.; Sakrikar D; The Binding Site, Rochester, MN, USA.; Barnidge D; The Binding Site, Rochester, MN, USA.; Bustoros M; Department of Medical Oncology, Weill Cornell Medicine, New York, NY, USA.; Leblebjian H; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA; Department of Pharmacy, Dana-Farber Cancer Institute, Boston, MA, USA.; Cowan A; Alix School of Medicine, The Mayo Clinic, Rochester, MN, USA.; Davis MI; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA; Harvard Medical School, Boston, MA, USA.; Amstutz J; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA; Harvard Medical School, Boston, MA, USA.; Boehner CJ; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA; Harvard Medical School, Boston, MA, USA.; Lightbody ED; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA; Harvard Medical School, Boston, MA, USA.; Sklavenitis-Pistofidis R; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA; Harvard Medical School, Boston, MA, USA; Broad Institute of MIT and Harvard, Cambridge, MA, USA.; Perkins MC; The Binding Site Group, Birmingham, UK.; Harding S; The Binding Site Group, Birmingham, UK.; Mo CC; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA; Harvard Medical School, Boston, MA, USA.; Kapoor P; The Mayo Clinic, Rochester, MN, USA.; Mikhael J; Translational Genomics Research Institute, City of Hope Cancer Center, Phoenix, AZ, USA; International Myeloma Foundation, North Hollywood, CA, USA.; Borrello IM; Department of Medical Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.; Fonseca R; Department of Medical Oncology, The Mayo Clinic, Phoenix, AZ, USA.; Weiss ST; Harvard Medical School, Boston, MA, USA; Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA.; Karlson E; Harvard Medical School, Boston, MA, USA; Division of Rheumatology, Inflammation, and Immunity, Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA.; Trippa L; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.; Rebbeck TR; The Center for Prevention of Progression of Blood Cancer, Dana-Farber Cancer Institute, Boston, MA, USA.; Getz G; Harvard Medical School, Boston, MA, USA; Center for Cancer Research, Massachusetts General Hospital, Boston, MA, USA; Broad Institute of MIT and Harvard, Cambridge, MA, USA.; Marinac CR; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA; The Center for Prevention of Progression of Blood Cancer, Dana-Farber Cancer Institute, Boston, MA, USA; Harvard Medical School, Boston, MA, USA.; Ghobrial IM; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA; The Center for Prevention of Progression of Blood Cancer, Dana-Farber Cancer Institute, Boston, MA, USA; Harvard Medical School, Boston, MA, USA. Electronic address: irene_ghobrial@dfci.harvard.edu. |
| Source: | The Lancet. Haematology [Lancet Haematol] 2022 May; Vol. 9 (5), pp. e340-e349. Date of Electronic Publication: 2022 Mar 25. |
| Publication Type: | Journal Article; Multicenter Study |
| Language: | English |
| Journal Info: | Publisher: Elsevier Ltd Country of Publication: England NLM ID: 101643584 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2352-3026 (Electronic) Linking ISSN: 23523026 NLM ISO Abbreviation: Lancet Haematol Subsets: MEDLINE |
| Imprint Name(s): | Original Publication: [Oxford] : Elsevier Ltd., [2014]- |
| MeSH Terms: | Monoclonal Gammopathy of Undetermined Significance*/epidemiology ; Multiple Myeloma*/epidemiology ; Paraproteinemias*/diagnosis ; Paraproteinemias*/epidemiology; Cohort Studies ; Female ; Humans ; Male ; Mass Spectrometry ; Prevalence |
| Abstract: | 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 ClinicalTrials.gov, 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 ( |
| Competing Interests: | Declaration of interests DS, DB, MCP are current employees of The Binding Site. MB is a consultant for Takeda and has received honoraria from Takeda, Janssen, and Bristol Myers Squibb (BMS). SH is a current employee, member of the Board of Directors, and holds patents related to The Binding Site. CCM is a consultant for Eli Lilly and Epizyme, is an advisory board member for BMS, has served as a consultant and advisory board member for GlaxoSmithKline (GSK), has received honoraria from Janssen, Karyopharm, and Sanofi; and served as an advisory board member for Karyopharm and Sanofi. PK is a principal investigator of studies for which Mayo Clinic has received research funding from AbbVie, Sanofi, Amgen, GSK, Ichnos, Takeda, Regeneron, and Karyopharm; and has received honoraria from X4 pharmaceuticals, Beigene, Pharmacyclics, Imidex, Clinical Care Options, GSK, Oncopeptides, Cellectar, and Karyopharm. JM is a consultant for Amgen, BMS, GSK, Janssen, Karyopharm, Sanofi, and Takeda. RF is a consultant for AbbVie, Amgen, Bayer, BMS/Celgene, GSK, H3 Therapeutics, Janssen, Juno, Karyopharm, Kite, Merck, Novartis, Oncopeptides, OncoTracker, Pfizer, Pharmacyclics, Regeneron, Sanofi, and Takeda; and is on scientific advisory board of Adaptive Biotechnologies, Caris Life Sciences, OncoMyx, and OncoTracker. GG receives research funds from International Business Machines Corporation and Pharmacyclics and is an inventor on patent applications related to MSMuTect, MSMutSig, MSIDetect, POLYSOLVER, SignatureAnalyzer-GPU and TensorQTL. GG is a founder, consultant and holds privately held equity in Scorpion Therapeutics. CRM has serves as a consultant for JBF Legal and received research funding from GRAIL. IMG has served as a consultant for AbbVie, Adaptive, Aptitude Health, BMS, Cellectar, CurioScience, Genetch, Janssen, Janssen Central American and Caribbean, Karyopharm, Medscape, Oncopeptides, Sanofi, Takeda, The Binding Site, Gene Network Sciences Healthcare, and GSK. IMG's spouse, William Savage is CMO and equity holder at Disc Medicine. All other authors declare no competing interest. |
| Comments: | Comment in: Lancet Haematol. 2022 May;9(5):e315-e317. doi: 10.1016/S2352-3026(22)00101-6.. (PMID: 35344690) |
| References: | N Engl J Med. 2006 Mar 30;354(13):1362-9. (PMID: 16571879); Blood. 2006 Feb 1;107(3):904-6. (PMID: 16210333); Blood. 2009 May 28;113(22):5412-7. (PMID: 19179464); Am J Clin Pathol. 2012 Oct;138(4):609-13. (PMID: 23010717); Mayo Clin Proc. 2007 Dec;82(12):1468-73. (PMID: 18053453); Blood. 2010 Aug 19;116(7):1056-9. (PMID: 20421448); Blood. 2009 Jul 23;114(4):785-90. (PMID: 19179466); N Engl J Med. 2008 Jul 10;359(2):152-7. (PMID: 18614782); Blood Cancer J. 2021 Feb 5;11(2):19. (PMID: 33563912); Transplant Direct. 2019 Sep 19;5(10):e489. (PMID: 31723584); N Engl J Med. 2017 Jul 13;377(2):111-121. (PMID: 28636844); Lancet. 2010 May 15;375(9727):1721-8. (PMID: 20472173); Cell Rep. 2015 Mar 3;10(8):1239-45. (PMID: 25732814); Science. 2019 Jun 07;364(6444):. (PMID: 31171663); N Engl J Med. 2014 Dec 25;371(26):2488-98. (PMID: 25426837); Blood Cancer J. 2017 Oct 20;7(10):e618. (PMID: 29053158); Case Rep Med. 2012;2012:607104. (PMID: 23304158); Acta Med Scand. 1963 Jun;173:737-44. (PMID: 13952159); Blood. 1974 Aug;44(2):189-95. (PMID: 4369394); Am J Hematol. 2011 Jun;86(6):475-8. (PMID: 21544856); Acta Med Scand. 1966 Feb;179(2):235-47. (PMID: 4160039); Oncotarget. 2017 Nov 15;8(63):106333-106341. (PMID: 29290952); N Engl J Med. 2002 Feb 21;346(8):564-9. (PMID: 11856795); Blood. 2009 Jul 23;114(4):791-5. (PMID: 19182202); Br J Haematol. 2016 Oct;175(1):87-101. (PMID: 27330041); Blood Cancer J. 2018 Jun 12;8(6):59. (PMID: 29895887); Hum Pathol. 2018 May;75:154-158. (PMID: 29180248); Blood Cancer J. 2019 Dec 13;9(12):102. (PMID: 31836698) |
| Grant Information: | R25 AI147393 United States AI NIAID NIH HHS; K22 CA251648 United States CA NCI NIH HHS; R35 CA263817 United States CA NCI NIH HHS; R01 CA133799 United States CA NCI NIH HHS; R01 CA205954 United States CA NCI NIH HHS |
| Molecular Sequence: | ClinicalTrials.gov NCT03689595 |
| Entry Date(s): | Date Created: 20220328 Date Completed: 20220502 Latest Revision: 20250721 |
| Update Code: | 20260130 |
| PubMed Central ID: | PMC9067621 |
| DOI: | 10.1016/S2352-3026(22)00069-2 |
| PMID: | 35344689 |
| Database: | MEDLINE |
Journal Article; Multicenter Study