MGUS and Multiple Myeloma

Medically Reviewed by Sabrina Felson, MD on July 13, 2022
4 min read

Monoclonal gammopathy of undetermined significance (MGUS) is when small amounts of antibodies called monoclonal antibodies (or M antibodies) are found in your blood.

Normally, the plasma cells in your bone marrow (the soft, squishy stuff in the center of your bones) make antibodies that help your body fight infections. But when you have MGUS, your plasma cells make M antibodies. M antibodies are identical. They are not tailored to or helpful in protecting you against infections at all.

MGUS usually doesn’t cause problems or need treatment. But in rare cases – 1% to 2% of the time – it can turn into the blood cancer multiple myeloma. If you have MGUS, it’s important to check in with your doctor to make sure it doesn’t progress.

MGUS is grouped into three main groups based on the antibody subtype. The three groups have different symptoms and syndromes if they progress to multiple myeloma. Remember, MGUS very rarely has symptoms. The three categories of MGUS and multiple myeloma are:

  • Non-IgM MGUS (IgG, IgA, or IgD MGUS), the most common MGUS
  • Light chain MGUS (Kappa or Lambda)
  • IgM MGUS

They can also lead to AL amyloidosis if their monoclonal process includes light chains. AL amyloidosis is when abnormal proteins called amyloids build up in your organs and keep them from working the way they should.

Though it’s also a heavy chain, IgM MGUS is set apart because of its association with Waldenstrom macroglobulinemia. Also called lymphoplasmacytic lymphoma, it’s a rare type of cancer that starts in your white blood cells.

Age. You’re more likely to get MGUS if you’re over 50.

Sex. More men than women get MGUS and multiple myeloma.

Race. MGUS is seen more often in Africans and African Americans.

Family history. Research suggests that if you have a relative with MGUS, your risk is about three times higher than someone who doesn’t. Your odds of getting multiple myeloma and other blood cancers, such as chronic lymphocytic leukemia, are also higher. That said, many MGUS cases don’t appear to have this link. If you have at least two first-degree relatives (parent, sibling, or child) diagnosed with either MGUS or multiple myeloma, your doctor may recommend that you be tested for MGUS even if you don’t have symptoms.

Certain chemicals. If you were exposed to Agent Orange during the Vietnam War, you’re more than twice as likely as others to get MGUS.

People with MGUS usually have no symptoms. In the rare event of symptoms, tingling or numbness in your feet or hands may be because of MGUS.

If results on routine blood work are concerning for a monoclonal gammopathy, your doctor will run additional tests. These tests are done to see if there is a monoclonal antibody or pieces of antibody in your blood or urine. If there is a monoclonal antibody found, an extra step will be taken to identify the subtype. They’ll run the following tests:

  • Serum protein electrophoresis (SPEP)
  • Urine protein electrophoresis (UPEP)
  • Serum free light chains
  • Reflex immunofixation to identify what type of MGUS there is

If monoclonal gammopathy is found, the next step is to rule out multiple myeloma.

You’ll get these tests each year:

Blood tests. These will include a complete blood count to look for low blood cell counts. The doctor will check for high calcium levels from bone destruction and kidney damage from antibodies clogging their ability to filter and make urine. They will look for the amount of monoclonal protein in your blood. Greater than 3 gm/dL of monoclonal antibodies in the blood is suspicious for multiple myeloma.

Imaging tests. Your doctor may do yearly X-rays to look for lytic lesions, which are areas of bone destruction or even fractures caused by cancer cells.

Bone marrow test. If your blood comes back with a high M protein level, anemia, or your doctor suspects a lytic lesion, you may need a bone marrow biopsy. It’s when a needle is used to take a sample of bone marrow from one of your hip bones. A bone marrow biopsy with more than 10% monoclonal plasma cells is suspicious for multiple myeloma and is no longer MGUS.

MGUS isn’t treated because there is no treatment. Also, treating MGUS has not been shown to lower the risk of progression to cancer. That said, most people who have it live a normal life with no problems. Still, it’s important to check with your doctor about how often you should come in for monitoring.

The doctor will continue to run blood tests to check your creatine and calcium levels, among other things. They’ll also look for and ask about:

  • Bone pain
  • Fatigue
  • General weakness
  • Unintentional weight loss
  • Unexplained fever
  • Night sweats
  • Neuropathy (nerve damage)
  • Headache
  • Dizziness
  • Loss of vision
  • Loss of hearing
  • Bleeding
  • Enlarged tongue
  • Protein in your urine
  • Enlarged spleen or liver
  • Swelling of your lymph nodes