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 or a related condition. This can take months or years.

In MGUS, abnormal plasma cells (called myeloma cells) make one type of immunoglobulin( Ig) called an M-protein. There are 3 main types of MGUS depending on which immunoglobulin is involved.

IgM MGUS involves the IgM immunoglobulin. IgM MGUS may develop into Waldenstrom macroglobulinemia, amyloidosis, lymphoma or multiple myeloma.

Non-IgM MGUS is the most common type of MGUS. It involves immunoglobulins other than IgM – usually IgG or IgA immunoglobulins. Non-IgM MGUS may develop into multiple myeloma, solitary plasmacytoma or amyloidosis.

Light chain MGUS (LC MGUS) involves a light chain immunoglobulin. LC MGUS may develop into multiple myeloma, solitary plasmacytoma or amyloidosis.

MGUS usually develops in people 70 years of age or older. Black men (including men of African ancestry) and people with a family history of MGUS or multiple myeloma have a higher chance of developing MGUS.

MGUS is usually found when doing routine blood work or if multiple myeloma or Waldenstrom macroglobulinemia is suspected.

Many tests used to diagnose MGUS are used to diagnose multiple myeloma. The criteria to diagnose MGUS vary between IgM MGUS, non-IgM MGUS and LC MGUS. The main criteria for diagnosing MGUS are the following:

• The M-protein level in the blood is less than 30 g/L.
• The M-protein level in the urine is less than 500 mg over a 24-hour period.
• Myeloma cells make up less than 10% of the blood cells in the bone marrow.
• There are no CRAB features (signs) of multiple myeloma (high c alcium level, r enal insufficiency, a nemia or b one disease).

MGUS often doesn't have any signs or symptoms, but it may cause the following complications:

• Osteoporosis– Some bones may become weak due to the high number of myeloma cells in the bone marrow and cause an increased risk of fractures and bone pain.
• Infections– MGUS affects the immune system and can increase your risk for infections.

• Peripheral nerve damage (peripheral neuropathy)– IgM MGUS may cause tingling or numbness in your hands and feet.

In general, the risk of MGUS progressing to multiple myeloma is 1% each year and remains 1% each year you live with the disease. So, even 25 years after a diagnosis, the risk of MGUS progressing to multiple myeloma is still 1%.

MGUS doesn't always progress to multiple myeloma or other related conditions. Many people living with MGUS are in good health and the disease remains stable.

Recently, diagnostic tests have helped to identify which people with MGUS have a low risk and which have a high risk of developing multiple myeloma and other conditions including amyloidosis, solitary plasmacytoma or Waldenstrom macroglobulinemia.

Low-risk MGUS has all of the following features:

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

There is a 5% absolute risk of low-risk MGUS progressing to multiple myeloma or a related condition after 20 years.

High-risk MGUS has any of the following features:

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

If only one of the above features is present, there is a 21% absolute risk of MGUS progressing to multiple myeloma or a related condition after 20 years.

If 2 of the above features are present, there is a 37% absolute risk.

If all 3 of the above features are present, there is a 58% absolute risk.

When you are diagnosed with MGUS, you will be closely monitored (watched) by your healthcare team for signs of the disease progressing to multiple myeloma or a related condition. This is called watchful waiting. Other treatment is given when MGUS starts to progress to cancer.

During watchful waiting, you may have the following tests:

• health history and physical exam
• complete blood count (CBC)
• serum protein electrophoresis (SPEP)
• urinalysis to measure calcium and creatinine in the urine
• serum free light chain test

Follow-up visits are scheduled differently for low-risk MGUS and high-risk MGUS.

If you have low-risk MGUS, a follow-up visit is scheduled 6 months after diagnosis. If the disease is stable, follow-ups will be scheduled every 2 to 3 years until you start developing symptoms or signs that the MGUS is progressing.

If you have high-risk MGUS, a follow-up visit is scheduled 6 months after a diagnosis, then once every year until you start developing symptoms or signs that the MGUS is progressing.

Don't wait until your next scheduled appointment if you develop any signs or symptoms of multiple myeloma. Report any new symptoms or symptoms that don't go away.