What is monoclonal gammopathy of uncertain significance (MGUS)?

If your doctor has told you that you have monoclonal gammopathy of undetermined significance (MGUS) after a routine blood test, this means there is a small amount of abnormal protein in your blood.  

But what does this actually mean — and should you be concerned? We talked to multiple myeloma expert Krina Patel, M.D., to learn what MGUS is, whether it can turn into cancer and what follow-up care you may need.

What is MGUS? 

Plasma cells normally produce antibodies that help your body fight off infection. In MGUS, a small number of these cells start making large amounts of a single, ineffective antibody called an M-protein. When these abnormal cells make up less than 10% of the plasma cells in the bone marrow, it’s unlikely to cause organ damage and is then considered MGUS.

“The big question is whether that small clone will ever cause trouble,” says Patel. “For most people, it never does.”

Are there any symptoms of MGUS?

Although many people with MGUS never have any symptoms, some people with MGUS report having varying levels of neuropathy, fatigue or weakness. 

How is MGUS diagnosed?

Doctors may order a blood test if routine lab work shows higher-than-expected protein levels.

Specifically, they will look at the difference between total protein and albumin in the blood. If that gap is bigger than normal, it could be a sign that your body is making an abnormal protein, so additional tests are needed.

Your care team may then order: 

• Another blood test to see if your bloodwork shows an M-protein 
• A urine test to check if any abnormal protein is being filtered through the kidneys
• If the blood test shows an M-protein and the urine test does not show protein-related organ damage or signs of another disease, the findings point to MGUS.

Do people with MGUS develop multiple myeloma?

On average, MGUS progresses to blood cancers like multiple myeloma at a rate of about 1% per year.

This means that if you are diagnosed with MGUS at age 50, you have about a 20% chance of developing multiple myeloma by the time you’re 70.  

Who is at higher risk for MGUS?

MGUS becomes more common with age. About 3% of people over 50 have MGUS. That percentage rises with each decade, with about 1 in 3 people over age 80 having MGUS. 

MGUS also occurs more often in people who are Black and/or have a family history of multiple myeloma. 

“In the past, it was thought that autoimmune diseases may be related to the presence of M-proteins, but recent research has not found a direct link,” says Patel. 

Are any other conditions related to M-proteins?

Yes, there are some conditions that are related to MGUS. Although MGUS does not typically require treatment, you may need closer monitoring if you have one of these conditions: 

• Monoclonal gammopathy of renal significance (MGRS) happens when the M-protein or monoclonal light chains injure the kidneys. Signs can include foamy urine or rising creatinine. “If we find MGRS, we treat it to protect kidney function,” says Patel. 
• AL (light-chain) amyloidosis occurs when a specific type of amyloid protein made by abnormal plasma cells deposits in organs such as the heart, kidneys, gastrointestinal tract or tongue. Symptoms can include leg swelling, shortness of breath, weight loss, bowel changes or an enlarged tongue. Urine testing and targeted evaluations, such as biopsies, are used to diagnose this condition. 
• Monoclonal gammopathy of neurologic significance (MGNS) can cause significant numbness, tingling or burning pain. If you have these symptoms, your care team will first treat common causes like diabetes or vitamin B12 deficiency. If your symptoms are clearly linked to the M-protein and quality of life is poor, your doctor may recommend certain therapies to help. 

Other blood cancers, including Waldenström macroglobulinemia and chronic lymphocytic leukemia, can also produce an M-protein. If your test shows an M-protein and you have symptoms commonly linked to these diseases, such as fatigue, unexplained weight loss or swollen lymph nodes, your doctor will order additional tests to rule them out. 

How is MGUS monitored?

Follow-up care is personalized depending on your level of M-protein and other individual risk factors. Many people need labs once a year. If you have very low M-protein levels, your doctor may have you get lab work done every one to two years. Others need visits more often. 

Your doctor may repeat blood and urine protein tests, kidney tests and blood counts; they may add imaging or a bone marrow exam if numbers rise or symptoms appear. If your M-protein numbers start to go up, your doctor will reassess for smoldering myeloma, multiple myeloma or organ-involving conditions such as MGRS or AL amyloidosis.  

In very rare cases, someone will have an M-protein on their blood test and then it’s decreasing or gone the next time it is checked. “Your plasma cells make these proteins to help fight infections. So, it just depends on when we’re checking these sometimes. It could be a false-positive,” says Patel. 

UT MD Anderson has a dedicated MGUS Clinic to help people with MGUS get the care they need.

Patients receive a focused evaluation to rule out organ-involving conditions, a personalized follow-up plan, access to non-interventional research that helps us learn who progresses and why, and guidance on symptom management, lifestyle and when to call.  

“This clinic helps you get answers sooner, stay informed and step in early if anything changes,” says Patel. 

How can you manage anxiety after a MGUS diagnosis?

Anxiety is common. “It’s the uncertainty,” says Patel. “You feel fine, yet you’ve been told something could happen.” 

But it can help to learn what MGUS is, keep regular follow-up appointments and seek support. 

It also helps to remember that many people with MGUS never need treatment, and treatment options for myeloma continue to improve for those who do, thanks to new research advances.

“When labs are stable, we tell patients, ‘Go live your life until the next check,’” Patel says. 

Can you take anything to treat MGUS?

There is no proven supplement that prevents progression, and some over-the-counter products can be harmful or interact with treatment. 

Patel recommends focusing on eating healthy meals. Fill two-thirds of your plate with fruits, vegetables, whole grains, nuts and seeds, and fill the remaining one-third with lean proteins like fish, poultry or plant protein like tofu. 

She also recommends staying physically active at a level that is right for you. UT MD Anderson recommends aiming for at least 150 minutes of moderate or 75 minutes of vigorous exercise each week.  

If you’re dealing with neuropathy, non-drug options like acupuncture, scrambler therapy and safe exercise may help. 

Medicines such as gabapentin or pregabalin can also reduce symptoms.  

“These steps benefit heart and metabolic health, and they support you if you ever do need treatment,” says Patel. 

Request an appointment at UT MD Anderson online or call 1-877-632-6789.