MGUS: Monlonal Gammopathy of Unknown Significance – pro

Monoclonal gammopathy of undetermined significance (MGUS) is the most common of a spectrum of diseases called plasma cell dyscrasias. Its prevalence increases with increasing age and it is in majority clinically slient. The term MGUS denotes the presence of a monoclonal immunoglobulin (Ig), also called an M-protein, in the serum or urine in persons without evidence of multiple myeloma (MM), Waldenström macroglobulinemia (WM), amyloidosis (AL) or other lymphoproliferative disorders.

The consensus 2020 recommendations are not to treat low or intermediate risk MGUS, but to closely follow it. However, the guideline also recommend individualized decision to treat high-risk MDS.

The purpose of MGUS follow-up is to detect early transformation in order to initiate timely treatment, minimize major complications and prolong survival. Given the seriousness of certain complications and the relative ease with which testing for M-proteins can be added to other routine medical tests, regular follow-up is recommended for the vast majority of MGUS patients. Baseline investigations should be repeated in all patients at 6 months. If findings remain stable, most patients can be followed-up annually thereafter. More frequent monitoring may be indicated in intermediate- to high-risk patients, particularly if there is evidence of disease progression. (Bergstrom, D. J. et al., 2020), (Kyle, R., Durie, B., Rajkumar, S. et al., 2010).

Once these conditions have been ruled out, no farther workup or investigation is routinely recommended. Inital and subsequent testing is limited to:
•Include baseline measurements of serum vitamin B12 and RBC folate levels and a hypercoagulation profile.
•In addition, specific workup relative to the gammopathy should include 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.
•Serum protein electrophoresis should be repeated in 3 months after diagnosis. If the results are stable, medical assessment should be performed every 6-12 months.
If a patient has an IgM M-protein, aspiration and biopsy of the bone marrow and CT scanning of the abdomen may be useful in detecting WM or other lymphoproliferative disorders. If all these results are satisfactory, serum electrophoresis should be repeated in 2-3 months at the earliest, and, if the finding is stable, the test should be repeated at 6- to 12-month intervals. Serum and urine electrophoresis with immunofixation should be performed if the serum M-protein value increases or if other evidence of evolving MM or WM is observed. No treatment is recommended for patients with MGUS, until and if, it evolves into another plasma cell dyscrasia. Recently various subtypes are being defined based on advanced tests but this had not reached clinical use.

Tomasson, M. H., Ali, M., De Oliveira, V., Xiao, Q., Jethava, Y., Zhan, F.,  Bates, M. L. (2018), “The five-year overall survival rate is ~50%, with worse prognosis in older adults and some improvements with the use of newer, novel agents (bortezomib, thalidomide, or lenalidomide) [3,4].”

Holstein, S. A., Suman, V. J., & McCarthy, P. L. (2018), “In particular, lenalidomide is currently standard of care in the newly diagnosed setting, in the maintenance setting post-autologous stem cell transplant, as well as in the relapsed/refractory setting. While the combination of lenalidomide and various proteasome inhibitors has proven particularly effective, there are emerging data demonstrating the effectiveness of lenalidomide in combination with other important classes of drugs including the monoclonal antibodies.” – Monoclonal Gammopathy
•Guidelines for the investigation of newly detected M-proteins and the management of Monoclonal Gammopathy of Undetermined Significance (MGUS) UK Myeloma Forum and Nordic Myeloma Study Group (February 2009)

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. Aug 2009;84(8):685-93.

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

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

8.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. Jul 16 2009;

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