Monoclonal gammopathy of undetermined significance

Monoclonal gammopathy of undetermined significance (MGUS) is a precancerous condition and the most common plasma cell disorder. Precancerous conditions are not yet cancer, but there is a chance these abnormal changes will eventually become cancer. Over a period of months or years, multiple myeloma, amyloidosis, lymphoma, Waldenstrom macroglobulinemia or chronic lymphocytic leukemia (CLL) may develop. In MGUS, abnormal plasma cells make one type of immunoglobulin (Ig) called an M-protein.

People with MGUS have the following features:

  • The M-protein level in the blood is less than 30 g/L. The M-protein often stays at the same level for many years.
  • Plasma cells make up less than 10% of the blood cells in the bone marrow.
  • There is no tumour and there are no CRAB features (signs) of multiple myeloma (high calcium level, renal insufficiency, anemia or bone disease).

Risk factors

You have a higher chance of developing MGUS if you:

  • are 70 years of age or older
  • are a man
  • are of African descent
  • have a family history of MGUS

Signs and symptoms

People with MGUS do not have any signs or symptoms.

Diagnosis

If a routine blood or urine test shows a high level of protein, further tests will be done to make a diagnosis and rule out other plasma cell disorders such as multiple myeloma. Tests may include:

  • health history and physical exam
  • protein electrophoresis
  • urinalysis
  • serum free light chain test
  • quantitative immunoglobulin (Ig) test
  • complete blood count (CBC)
  • blood chemistry tests
  • bone marrow aspiration and biopsy
  • x-rays of most bones

Find out more about these diagnostic tests.

Treatments

People with MGUS are closely monitored (watched) for signs of the disease progressing to multiple myeloma or a related condition. The process of monitoring a person’s signs is called watchful waiting. Treatment is not given during watchful waiting. Some people may never need treatment. You will have a regular exam about once or twice a year, including:

  • physical exam
  • blood and urine tests to monitor M-protein levels

See a doctor if you develop any signs or symptoms of multiple myeloma. Don’t wait for your scheduled appointment to report a new sign or symptom. If it looks like the disease is starting to progress to cancer, doctors will start treatment.

Low-risk MGUS

People who have low-risk MGUS have the following features:

  • The M-protein level is less than 15 g/L.
  • The type of M-protein is IgG.
  • The free light chain ratio is normal.

Follow-up includes a serum protein electrophoresis (SPEP) in 6 to 12 months. If the results are normal you will be retested every 2–3 years. You should see a doctor if you develop any signs or symptoms – don’t wait for your follow-up appointment or test. If you have low-risk MGUS, you have a 2% risk of progressing to multiple myeloma or a related condition at 20 years.

High-risk MGUS

People who have high-risk MGUS have any of the following features:

  • The M-protein level is more than 15 g/L.
  • The type of M-protein is IgA or IgM.
  • The free light chain ratio is abnormal.

If you have all 3 of these features, you have a 58% risk of developing multiple myeloma or a related condition at 20 years. If you have 2 of these features, you have a 37% risk. If you have 1 feature, you have a 21% risk.

A person who has any of these features will usually have a bone marrow aspiration and biopsy to check the number and look of plasma cells in the bone marrow. People with IgM MGUS may also have a CT scan to look for enlarged lymph nodes which may be a sign of lymphoma or Waldenstrom macroglobulenemia. If results of these tests are normal, you will have a follow-up SPEP and CBC about every 6–12 months. But see a doctor if you develop any signs or symptoms – don’t wait for your follow-up appointment or test.

Expert review and references

  • Alberta Health Services. Multiple Myeloma Clinical Practice Guideline LYHE-003. Alberta Health Services; 2015: http://www.albertahealthservices.ca/assets/info/hp/cancer/if-hp-cancer-guide-lyhe003-multi-myeloma.pdf.
  • American Cancer Society. Multiple myeloma. Atlanta, GA: American Cancer Society; 2014: http://www.cancer.org/acs/groups/cid/documents/webcontent/003121-pdf.pdf.
  • Kyle RA, Rajkumar SV . Monoclonal gammopathy of undetermined significance. Wiernik PH, Goldman JM, Dutcher JP, Kyle RA (eds.). Neoplastic Diseases of the Blood. 5th ed. Springer; 2013: 38: 751-788.
  • Mushi NC, Anderson KC . Plasma cell neoplasms. DeVita VT Jr, Lawrence TS, & Rosenberg SA. Cancer: Principles and Practice of Oncology. 10th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins; 2015: 112: 1682-1719.
  • Myeloma Canada. Multiple Myeloma Patient Handbook. Third ed. Kirkland, QC: Myeloma Canada; 2014.
  • National Cancer Institute. Plasma Cell Neoplasms (Including Multiple Myeloma) Treatment PDQ®: Health Professional Version. National Cancer Institute; 2014: http://www.cancer.gov/cancertopics/pdq/treatment/myeloma/healthprofessional.
  • Rajkumar SV, Kyle RA, Lust JA . Monoclonal gammopathies of undetermined significance and smouldering multiple myeloma. Greer JP, Arber DA, Glader B, List AF, Means RT Jr, Paraskevas F, Rodgers GM, Foerster J, (eds.). Wintrobe's Clinical Hematology. 13th ed. Lippincott Williams & Wilkins; 2014: 97: 2029-2045.