Monoclonal Gammopathies of Undetermined Significance (MGUS) Treatment & Management

Updated: Sep 23, 2021
  • Author: Suzanne R Fanning, DO; Chief Editor: Emmanuel C Besa, MD  more...
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Approach Considerations

No treatment is recommended for patients with MGUS. [32]  Long-term follow-up is generally advised, given the risk of progression to lymphoproliferative malignancy. [39]

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.

MGUS-associated neuropathies are generally not treated, except in the case of a disabling IgM monoclonal gammopathy or IgG/A MGUS  associated with chronic inflammatory demyelinating neuropathy (CIDP). About 80% of patients with IgG/A MGUS CIDP respond to one of the typical CIDP treatments and some patients stabilize without therapy. [31]

The intensity of follow-up in patients with MGUS is 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, 32, 2]  If clinical trials of preventive strategies are available, patients at high risk for progression should be encouraged to participate. 

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.



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, 32] 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. [40]

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, 32]

European Myeloma Network guidelines recommend that followup consist of the following [3] :

  • 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. [32]

With IgM MGUS, which poses a high risk for malignant progression, some experts recommend more intensive follow-up, with twice-annual visits that include the following [41] :

  • Clinical assessment
  • CBC
  • Comprehensive metabolic panel
  • Serum protein electrophoresis
  • Serum FLC assay
  • Quantitative immunoglobulin serum electrophoresis

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]