Close
New

Medscape is available in 5 Language Editions – Choose your Edition here.

 

Monoclonal Gammopathies of Undetermined Significance Treatment & Management

  • Author: Suzanne R Fanning, DO; Chief Editor: Emmanuel C Besa, MD  more...
 
Updated: Dec 28, 2015
 

Approach Considerations

No treatment is recommended for patients with MGUS.[24] However, if preventive clinical trials are available, patients should be encouraged to participate.

If a patient has no other features of a plasma cell dyscrasia and if a serum M-spike is detected, complete assessment of the patient's general medical status is needed. The assessment should include the following:

  • Baseline measurements of serum vitamin B12 and red blood cell folate levels and a hypercoagulation profile
  • Specific workup relative to the gammopathy, with a bone marrow examination, skeletal radiography (including single views of the humeri and femurs and complete spinal with optional lateral views), and a 24-hour urine collection for protein quantitation

If a patient has an IgM M-protein, aspiration and biopsy of the bone marrow and computed tomography (CT) scanning of the abdomen may be useful in detecting Waldenström macroglobulinemia or other lymphoproliferative disorders.

Patients with MGUS require lifelong follow-up, with the intensity of follow-up guided by risk stratification. Typically, initial follow-up at 6 months is recommended, with subsequent visits scheduled according to level of risk (see Long-Term Monitoring).[3, 24, 2]

Serum and urine electrophoresis with immunofixation should be performed if the serum M-protein value increases or if other evidence of evolving multiple myeloma or Waldenström macroglobulinemia is observed.

Next

Long-Term Monitoring

Current guidelines suggest lifelong followup in patients with MGUS, so that malignant transformation can be identified early, before the onset of serious complications.[3, 24] Sigurdardottir et al reported significantly better overall survival in patients with MM who had prior knowledge of MGUS than in those without prior knowledge (median survival, 2.8 years versus 2.1 years, respectively; hazard ratio 1.86; 95% confidence index, 1.13-3.04; P = 0.01), suggesting that earlier treatment of MM leads to improved survival.[30]

Followup schedules in patients with MGUS can be based on risk stratification. Various risk prediction models exist, using a variety of risk factors (eg, serum M-protein level ≥1.5 g/dL, non-IgG M-protein, and abnormal free light chain [FLC] ratio; or ≥95% aberrant plasma cells in bone marrow and DNA aneuploidy on flow cytometry).[3, 24]

European Myeloma Network guidelines recommend that followup consist of the following[24] :

  • History and physical examination
  • Serum M-protein electrophoresis
  • Complete blood cell count (CBC)
  • Serum creatinine assay
  • Serum calcium assay

The International Myeloma Working Group (IMWG) recommends followup serum protein electrophoresis for patients with MGUS 6 months after diagnosis, with subsequent followup depending on risk. The IMWG considers patients with IgG MGUS who have an M-protein level below 1.5 g/dL and a normal FLC ratio to be at low risk; if findings at 6 months are stable, subsequent follow-up can be every 2 to 3 years thereafter or when symptoms suggestive of a plasma cell malignancy arise. For patients with intermediate and high-risk MGUS, the IMWG recommends annual follow-up.[24]

With IgM MGUS, which poses a high risk for malignant progression, some experts recommend more intensive follow-up, with twice-annual visits that include clinical assessment, CBC, comprehensive metabolic panel, serum protein electrophoresis, serum FLC assay, and quantitative immunoglobulinsserum electrophoresis.[31]

The European Myeloma Network advises that for low-risk MGUS, follow-up at 6 months and every 1–2 years thereafter can be justified. Alternatively, follow-up for low-risk MGUS may be limited to performing laboratory studies or bone marrow analysis when patients develop symptoms suggestive of MM or related diseases. In patients who are elderly or have significant morbidity with a short life expectancy, it may be reasonable to forgo follow-up.[3]

 

 

Previous
 
 
Contributor Information and Disclosures
Author

Suzanne R Fanning, DO Fellow, Department of Hematology and Medical Oncology, Cleveland Clinic Foundation, 2004-2007 Director, Hematology, Greenville Memorial Health System, Greenville, SCMedical Oncologist/Hematologist/Transplant Pysician, 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 of Hematology, American Society for Blood and Marrow Transplantation, American Society of Clinical Oncology

Disclosure: Received consulting fee from Millenium Pharmaceuticals for review panel membership; Received consulting fee from Celgene Pharmaceuticals for review panel membership.

Coauthor(s)

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: Nothing to disclose.

Specialty Editor Board

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.

Chief Editor

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.

Additional Contributors

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.

References
  1. Bida JP, Kyle RA, Therneau TM, Melton LJ 3rd, Plevak MF, Larson DR, et al. Disease associations with monoclonal gammopathy of undetermined significance: a population-based study of 17,398 patients. Mayo Clin Proc. 2009 Aug. 84(8):685-93. [Medline]. [Full Text].

  2. Uddin Z, Maennle D, Russell K, Boltri JM. Monoclonal gammopathy of undetermined significance: Using risk stratification to guide follow-up. J Fam Pract. 2015 Jul. 64 (7):E5-E12. [Medline]. [Full Text].

  3. [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. [Medline]. [Full Text].

  4. Kyle RA, Therneau TM, Rajkumar SV, et al. Long-term follow-up of IgM monoclonal gammopathy of undetermined significance. Blood. 2003 Nov 15. 102(10):3759-64. [Medline].

  5. 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.

  6. 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.

  7. 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. [Medline].

  8. 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.

  9. 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. [Medline].

  10. Kyle RA, Therneau TM, Rajkumar SV, et al. A long-term study of prognosis in monoclonal gammopathy of undetermined significance. N Engl J Med. 2002 Feb 21. 346(8):564-9. [Medline].

  11. 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. [Medline]. [Full Text].

  12. 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. [Medline].

  13. 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. [Medline].

  14. 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. [Medline]. [Full Text].

  15. Landgren O, Gridley G, Turesson I, 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.

  16. 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. [Medline].

  17. Rajkumar SV, Kyle RA, Therneau TM, 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.

  18. 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. [Medline]. [Full Text].

  19. Cohen AL, Sarid R. The relationship between monoclonal gammopathy of undetermined significance and venous thromboembolic disease. Thromb Res. 2009 Feb 2. [Medline].

  20. 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.

  21. 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. [Medline].

  22. 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. [Medline].

  23. 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. [Medline]. [Full Text].

  24. [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. [Medline].

  25. 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.

  26. Katzmann JA, Kyle RA, Benson J, et al. Screening panels for detection of monoclonal gammopathies. Clin Chem. 2009 Aug. 55(8):1517-22. [Medline].

  27. 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. [Medline].

  28. 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.

  29. 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. [Medline].

  30. 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. [Medline].

  31. 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. September 15, 2014; Accessed: December 24, 2015.

  32. Madan S, Greipp PR. The incidental monoclonal protein: Current approach to management of monoclonal gammopathy of undetermined significance (MGUS). Blood Rev. 2009 Aug 19. epub ahead of print. [Medline].

  33. 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. [Medline].

  34. Davies FE, Dring AM, Li C, et al. Insights into the multistep transformation of MGUS to myeloma using microarray expression analysis. Blood. 2003 Dec 15. 102(13):4504-11.

  35. Decaux O, Laurat E, Perlat A, et al. Systemic manifestations of monoclonal gammopathy. Eur J Intern Med. 2009 Sep. 20(5):457-61. [Medline].

  36. Feinman R, Sawyer J, Hardin J, Tricot G. Cytogenetics and molecular genetics in multiple myeloma. Hematol Oncol Clin North Am. 1997 Feb. 11(1):1-25. [Medline].

  37. Fonesca R, Bailey RJ, Ahmann GJ, et al. Genomic abnormalities in monoclonal gammopathy of undetermined significance. Blood. 2002. 100:1417-1424.

  38. Korac P, Peran I, Skrtic A, et al. FOXP1 expression in monoclonal gammopathy of undetermined significance and multiple myeloma. Pathol Int. 2009 May. 59(5):354-8. [Medline].

  39. Kumar S, Rajkumar SV, Kyle RA, et al. Prognostic value of circulating plasma cells in monoclonal gammopathy of undetermined significance. J Clin Oncol. 2005 Aug 20. 23(24):5668-74.

  40. Kyle RA, Therneau TM, Rajkumar SV, et al. Prevalence of monoclonal gammopathy of undetermined significance. New England Journal of Medicine. 2006. 354:1362-1369.

  41. Rajkumar SV. MGUS and Smoldering Multiple Myeloma: Update on Pathogenesis, Natural History, and Management. Hematology (Am Soc Hematol Educ Program). 2005. 340-5.

 
Previous
Next
 
 
 
 
All material on this website is protected by copyright, Copyright © 1994-2016 by WebMD LLC. This website also contains material copyrighted by 3rd parties.