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Sections Monoclonal Gammopathies of Undetermined Significance (MGUS)
- Overview
- Presentation
- DDx
- Workup
- Treatment
- Medication
- Questions & Answers
- References
Medication Summary
No treatment is recommended for patients with uncomplicated monoclonal gammopathy of undetermined significance (MGUS). Treatment recommendations for patients with monoclonal gammopathy of clinical significance (ie, those with signs and symptoms referable to nerves, kidneys, and/or skin) are largely anecdotal. [7, 6] However, in patients with monoclonal gammopathy of renal significance (MGRS), management follows the treatment algorithm for multiple myeloma in cases of non‐IgM– and free light chain–associated MGRS, and follows that for Waldenström macroglobulinemia in cases of IgM‐associated MGRS. [7]
For several of the neurologic and dermatologic conditions, intravenous immunoglobulin, rituximab, and plasma cell–directed therapy have shown benefit. [6] For example, a prospective open-label trial by Niermeijer et al in 17 patients with IgM MGUS polyneuropathy found that treatment with rituximab was associated with improvement in three impairment measures, and no serious adverse events. [54]
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Bridoux F, Leung N, Hutchison CA, Touchard G, Sethi S, Fermand JP, et al. Diagnosis of monoclonal gammopathy of renal significance. Kidney Int. 2015 Apr. 87 (4):698-711. [QxMD MEDLINE Link]. [Full Text].
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Castillo JJ, Callander NS, Baljevic M, Sborov DW, Kumar S. The evaluation and management of monoclonal gammopathy of renal significance and monoclonal gammopathy of neurological significance. Am J Hematol. 2021 Jul 1. 96 (7):846-853. [QxMD MEDLINE Link]. [Full Text].
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[Guideline] van de Donk NW, Palumbo A, Johnsen HE, Engelhardt M, Gay F, et al. The clinical relevance and management of monoclonal gammopathy of undetermined significance and related disorders: recommendations from the European Myeloma Network. Haematologica. 2014 Jun. 99 (6):984-96. [QxMD MEDLINE Link]. [Full Text].
Derman B, Castillo JJ, Sarosiek S, Beksac M. When a Monoclonal Gammopathy Is Not Multiple Myeloma. Am Soc Clin Oncol Educ Book. 2022 Apr. 42:1-10. [QxMD MEDLINE Link].
Castaneda-Avila MA, Ulbricht CM, Epstein MM. Risk factors for monoclonal gammopathy of undetermined significance: a systematic review. Ann Hematol. 2021 Apr. 100 (4):855-863. [QxMD MEDLINE Link]. [Full Text].
Genet P, Sutton L, Chaoui D, Al Jijakli A, Gerbe J, Masse V, et al. Prevalence of monoclonal gammopathy in HIV patients in 2014. J Int AIDS Soc. 2014. 17(4 Suppl 3):19649. [QxMD MEDLINE Link]. [Full Text].
Hofmann JN, Beane Freeman LE, Murata K, Andreotti G, Shearer JJ, Thoren K, et al. Lifetime Pesticide Use and Monoclonal Gammopathy of Undetermined Significance in a Prospective Cohort of Male Farmers. Environ Health Perspect. 2021 Jan. 129 (1):17003. [QxMD MEDLINE Link]. [Full Text].
Georgakopoulou R, Andrikopoulou A, Sergentanis TN, Fiste O, Zagouri F, Gavriatopoulou M, et al. Overweight/Obesity and Monoclonal Gammopathy of Undetermined Significance. Clin Lymphoma Myeloma Leuk. 2021 Jun. 21 (6):361-367. [QxMD MEDLINE Link].
Kyle RA, Larson DR, Therneau TM, Dispenzieri A, Kumar S, Cerhan JR, et al. Long-Term Follow-up of Monoclonal Gammopathy of Undetermined Significance. N Engl J Med. 2018 Jan 18. 378 (3):241-249. [QxMD MEDLINE Link]. [Full Text].
Kaufmann H, Ackermann J, Baldia C, et al. Both IGH translocations and chromosome 13q deletions are early events in monoclonal gammopathy of undetermined significance and do not evolove during transition to multiple myeloma. Leukemia. 2004. 18:1879-1882.
Chang WJ, Van Wier SA, Ahmann GJ, et al. A validated FISH trisomy index demonstrates the hyperdiploid and nonhyperdiploid dichotomy in MGUS. Blood. 2005 Sep 15. 106(6):2156-61.
Ogmundsdottir HM, Einarsdottir HK, Steingrimsdottir H, Haraldsdottir V. Familial predisposition to monoclonal gammopathy of unknown significance, Waldenstrom's macroglobulinemia, and multiple myeloma. Clin Lymphoma Myeloma. 2009 Mar. 9(1):27-9. [QxMD MEDLINE Link].
Fenhuang Z, Barlogie B, Arzoumanian, et al. Gene-expression signature of benign monoclonal gammopathy evident in multiple myelom is linked to good prognosis. Blood. 2007. 109:1692-1700.
Nagoshi H, Taki T, Chinen Y, Tatekawa S, Tsukamoto T, Maegawa S, et al. Transcriptional dysregulation of the deleted in colorectal carcinoma gene in multiple myeloma and monoclonal gammopathy of undetermined significance. Genes Chromosomes Cancer. 2015 Dec. 54 (12):788-95. [QxMD MEDLINE Link].
Mullikin TC, Rajkumar SV, Dispenzieri A, Buadi FK, Lacy MQ, Lin Y, et al. Clinical characteristics and outcomes in biclonal gammopathies. Am J Hematol. 2016 May. 91 (5):473-5. [QxMD MEDLINE Link].
Kyle RA, Therneau TM, Rajkumar SV, Larson DR, Plevak MF, Offord JR, et al. Prevalence of monoclonal gammopathy of undetermined significance. N Engl J Med. 2006 Mar 30. 354 (13):1362-9. [QxMD MEDLINE Link]. [Full Text].
Murray D, Kumar SK, Kyle RA, Dispenzieri A, Dasari S, Larson DR, et al. Detection and prevalence of monoclonal gammopathy of undetermined significance: a study utilizing mass spectrometry-based monoclonal immunoglobulin rapid accurate mass measurement. Blood Cancer J. 2019 Dec 13. 9 (12):102. [QxMD MEDLINE Link]. [Full Text].
Han JH, Wang JN, Zhang YL, Cao XX, Zhou DB, Xu TD, et al. Prevalence of monoclonal gammopathy of undetermined significance in a large population with annual medical check-ups in China. Blood Cancer J. 2020 Mar 9. 10 (3):34. [QxMD MEDLINE Link]. [Full Text].
Landgren O, Shim YK, Michalek J, Costello R, Burton D, Ketchum N, et al. Agent Orange Exposure and Monoclonal Gammopathy of Undetermined Significance: An Operation Ranch Hand Veteran Cohort Study. JAMA Oncol. 2015 Nov 1. 1 (8):1061-8. [QxMD MEDLINE Link].
Landgren O, Zeig-Owens R, Giricz O, Goldfarb D, Murata K, Thoren K, et al. Multiple Myeloma and Its Precursor Disease Among Firefighters Exposed to the World Trade Center Disaster. JAMA Oncol. 2018 Jun 1. 4 (6):821-827. [QxMD MEDLINE Link].
Kristinsson SY, Björkholm M, Landgren O. Survival in monoclonal gammopathy of undetermined significance and waldenström macroglobulinemia. Clin Lymphoma Myeloma Leuk. 2013 Apr. 13(2):187-90. [QxMD MEDLINE Link].
Kristinsson SY, Bjorkholm M, Andersson TM, et al. Patterns of survival and causes of death following a diagnosis of monoclonal gammopathy of undetermined significance (MGUS): a population-based study. Haematologica. 2009 Jul 16. epub ahead of print. [QxMD MEDLINE Link]. [Full Text].
Kyle RA, Larson DR, Therneau TM, Dispenzieri A, Kumar S, Cerhan JR, et al. Long-Term Follow-up of Monoclonal Gammopathy of Undetermined Significance. N Engl J Med. 2018 Jan 18. 378 (3):241-249. [QxMD MEDLINE Link]. [Full Text].
Landgren O, Gridley G, Turesson I, Caporaso NE, Goldin LR, Baris D, et al. Risk of monoclonal gammopathy of undetermined significance (MGUS) and subsequent multiple myeloma among African American and white veterans in the United States. Blood. 2006 Feb 1. 107 (3):904-6. [QxMD MEDLINE Link]. [Full Text].
Landgren O, Weiss BM. Patterns of monoclonal gammopathy of undetermined significance and multiple myeloma in various ethnic/racial groups: support for genetic factors in pathogenesis. Leukemia. 2009 Jul 9. [QxMD MEDLINE Link].
Rajkumar SV, Kyle RA, Therneau TM, Melton LJ 3rd, Bradwell AR, Clark RJ, et al. Serum free light chain ratio is an independent risk factor for progression in monoclonal gammopathy of undetermined significance. Blood. 2005 Aug 1. 106 (3):812-7. [QxMD MEDLINE Link]. [Full Text].
Pelzer BW, Arendt M, Moebus S, Eisele L, Jöckel KH, Dührsen U, et al. Light chain monoclonal gammopathy of undetermined significance is characterized by a high disappearance rate and low risk of progression on longitudinal analysis. Ann Hematol. 2018 Aug. 97 (8):1463-1469. [QxMD MEDLINE Link].
Turesson I, Kovalchik SA, Pfeiffer RM, Kristinsson SY, Goldin LR, Drayson MT, et al. Monoclonal gammopathy of undetermined significance and risk of lymphoid and myeloid malignancies: 728 cases followed up to 30 years in Sweden. Blood. 2014 Jan 16. 123(3):338-45. [QxMD MEDLINE Link]. [Full Text].
Baldursdóttir TR, Löve ÞJ, Gíslason GK, Björkholm M, Mellqvist UH, Lund SH, et al. Autoimmune disease is associated with a lower risk of progression in monoclonal gammopathy of undetermined significance. Eur J Haematol. 2021 Mar. 106 (3):380-388. [QxMD MEDLINE Link].
Pang L, Rajkumar SV, Kapoor P, Buadi F, Dispenzieri A, Gertz M, et al. Prognosis of young patients with monoclonal gammopathy of undetermined significance (MGUS). Blood Cancer J. 2021 Feb 1. 11 (2):26. [QxMD MEDLINE Link]. [Full Text].
Cohen AL, Sarid R. The relationship between monoclonal gammopathy of undetermined significance and venous thromboembolic disease. Thromb Res. 2009 Feb 2. [QxMD MEDLINE Link].
Srkalovic G, Cameron MG, Rybicki L, et al. Monoclonal gammopathy of undetermined significance and multiple myeloma are associated with an increased incidence of venothromboembolic disease. Cancer. 2004 Aug 1. 101(3):558-66.
Kristinsson SY, Tang M, Pfeiffer RM, et al. Monoclonal gammopathy of undetermined significance and risk of skeletal fractures: a population-based study. Blood. 2010 Oct 14. 116(15):2651-5. [QxMD MEDLINE Link].
Piot JM, Royer M, Schmidt-Tanguy A, Hoppé E, Gardembas M, Bourrée T, et al. Factors associated with an increased risk of vertebral fracture in monoclonal gammopathies of undetermined significance. Blood Cancer J. 2015 Aug 28. 5:e345. [QxMD MEDLINE Link].
Kristinsson SY, Tang M, Pfeiffer RM, Björkholm M, Goldin LR, Blimark C, et al. Monoclonal gammopathy of undetermined significance and risk of infections: a population-based study. Haematologica. 2012 Jun. 97 (6):854-8. [QxMD MEDLINE Link]. [Full Text].
Jain A, Haynes R, Kothari J, Khera A, Soares M, Ramasamy K. Pathophysiology and management of monoclonal gammopathy of renal significance. Blood Adv. 2019 Aug 13. 3 (15):2409-2423. [QxMD MEDLINE Link]. [Full Text].
Rison RA, Beydoun SR. Paraproteinemic neuropathy: a practical review. BMC Neurol. 2016 Jan 28. 16:13. [QxMD MEDLINE Link]. [Full Text].
[Guideline] Kyle RA, et al; International Myeloma Working Group. Monoclonal gammopathy of undetermined significance (MGUS) and smoldering (asymptomatic) multiple myeloma: IMWG consensus perspectives risk factors for progression and guidelines for monitoring and management. Leukemia. 2010 Jun. 24 (6):1121-7. [QxMD MEDLINE Link].
Swerdlow SH, Campro E, Harris NL, et al. World Health Organization Classification of Tumours of Haematopoietic and Lymphoid Tissues. 4th ed. Lyon, France: IARC; 2008.
D'Souza A. Monoclonal Gammopathy of Renal Significance. American Society of Hematology - Ask The Hematologist. Available at https://www.hematology.org/Thehematologist/Ask/9059.aspx. November-December 2018; Accessed: December 27, 2019.
Katzmann JA, Kyle RA, Benson J, et al. Screening panels for detection of monoclonal gammopathies. Clin Chem. 2009 Aug. 55(8):1517-22. [QxMD MEDLINE Link].
Greenberg AJ, Cousin M, Kumar S, Ketterling RP, Knudson RA, Larson D, et al. Differences in the distribution of cytogenetic subtypes between multiple myeloma patients with and without a family history of monoclonal gammopathy and multiple myeloma. Eur J Haematol. 2013 May 6. [QxMD MEDLINE Link].
Ng AP, Wei A, Bhurani D, et al. The sensitivity of CD138 immunostaining of bone marrow trephine specimens for quantifying marrow involvement in MGUS and myeloma, including samples with a low percentage of plasma cells. Haematologica. 2006. 91:972-975.
Jerez A, Ortuno FJ, Osma MD, et al. Bone-marrow immunophenotypic analysis allows the identification of high risk of progression and immune condition-related monoclonal gammopathy of undetermined significance. Ann Med. 2009 Jul 26. 1-12. [QxMD MEDLINE Link].
Go RS, Rajkumar SV. How I manage monoclonal gammopathy of undetermined significance. Blood. 2018 Jan 11. 131 (2):163-173. [QxMD MEDLINE Link].
Sigurdardottir EE, Turesson I, Lund SH, Lindqvist EK, Mailankody S, Korde N, et al. The Role of Diagnosis and Clinical Follow-up of Monoclonal Gammopathy of Undetermined Significance on Survival in Multiple Myeloma. JAMA Oncol. 2015 May. 1 (2):168-74. [QxMD MEDLINE Link].
Mikhael J. Ask the Hematologist: A Diagnostic Approach to Patients with an IgM monoclonal protein. American Society of Hematology. Available at http://www.hematology.org/Thehematologist/Ask/3186.aspx. August 3, 2016; Accessed: December 27, 2019.
Niermeijer JM, Eurelings M, Lokhorst HL, et al. Rituximab for polyneuropathy with IgM monoclonal gammopathy. J Neurol Neurosurg Psychiatry. 2009 Sep. 80(9):1036-9. [QxMD MEDLINE Link].
Tables
Suzanne R Fanning, DO Director of Hematology, Greenville Memorial Health System; Medical Oncologist/Hematologist/Transplant Physician, Cancer Centers of the Carolinas
Suzanne R Fanning, DO is a member of the following medical societies: American College of Physicians, American Medical Association, American Society for Blood and Marrow Transplantation, American Society of Clinical Oncology, American Society of Hematology
Disclosure: Received consulting fee from Millenium Pharmaceuticals for review panel membership; Received consulting fee from Celgene Pharmaceuticals for review panel membership.
Mohamad A Hussein, MD Clinical Director, Malignant Hematology, Moffitt Cancer Center
Mohamad A Hussein, MD is a member of the following medical societies: American Association of Blood Banks, American College of Physicians, American Medical Association, American Society of Hematology
Disclosure: Received income in an amount equal to or greater than $250 from: Celgene corporation.
Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference
Disclosure: Received salary from Medscape for employment. for: Medscape.
Emmanuel C Besa, MD Professor Emeritus, Department of Medicine, Division of Hematologic Malignancies and Hematopoietic Stem Cell Transplantation, Kimmel Cancer Center, Jefferson Medical College of Thomas Jefferson University
Emmanuel C Besa, MD is a member of the following medical societies: American Association for Cancer Education, American Society of Clinical Oncology, American College of Clinical Pharmacology, American Federation for Medical Research, American Society of Hematology, New York Academy of Sciences
Disclosure: Nothing to disclose.
Karen Seiter, MD Professor, Department of Internal Medicine, Division of Oncology/Hematology, New York Medical College
Karen Seiter, MD is a member of the following medical societies: American Association for Cancer Research, American College of Physicians, American Society of Hematology
Disclosure: Received honoraria from Novartis for speaking and teaching; Received consulting fee from Novartis for speaking and teaching; Received honoraria from Celgene for speaking and teaching.
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Sections Monoclonal Gammopathies of Undetermined Significance (MGUS)
- Overview
- Presentation
- DDx
- Workup
- Treatment
- Medication
- Questions & Answers
- References
