MGUS

MGUS, or monoclonal gammopathy of undetermined significance, is a non-cancerous condition where a small number of abnormal cells in your bone marrow (the spongy centre of our bones) produces an abnormal protein that is detectable in the bloodstream. This abnormal protein is called paraprotein or M protein. 

We have outlined some key information about MGUS on this webpage.

If you would like to read more, see our Monoclonal gammopathy of undetermined significance (MGUS) infohseet.

Plasma cells, immunoglobulins and MGUS

The abnormal cells that are responsible for causing MGUS come from plasma cells. Plasma cells are a type of white blood cell found in the bone marrow and form an important part of our immune system. Healthy plasma cells make antibodies (which are also called immunoglobulins), to help fight infection.  

In MGUS, some of these plasma cells become abnormal because of DNA changes. Instead of producing useful antibodies, they produce paraprotein, which doesn’t have any useful function in your body.  

To read more about paraprotein, see our Understanding paraprotein in myeloma infosheet.

Most of the time, MGUS doesn’t cause symptoms, and you may only find out you have it by chance when you’re having blood tests done for another reason. 

Monitoring MGUS is important because each year, about 1% (1 in 100) people with MGUS will slowly progress to develop myeloma, a form of blood cancer that requires treatment.  

I received a letter from the blood bank saying that the routine test on my latest blood donation had shown a low level paraprotein count and that I should see my GP for further investigation. My GP did further tests and referred me to a haematologist, who confirmed I have MGUS. We found the ‘not knowing and waiting’ was quite unsettling for both myself and my wife

– Simon, Tasmania

What causes MGUS?

The cause of MGUS is not yet known, although researchers believe that there are genetic and environmental factors involved.  

We do know that some factors increase the risk of developing MGUS: 

• Age: MGUS is more common as you get older, especially after 55. 
• Ethnicity: MGUS is more common in people of Black ethnicity. 
• Family history: If someone in your family has MGUS, you have a higher chance of developing it too. 

How is MGUS diagnosed?

Part of MGUS’ definition is that it does not cause any symptoms. This means that MGUS is usually diagnosed when a paraprotein is found by chance when you’re having a routine check-up, or tests for other health conditions.  

Once the paraprotein has been found, your doctor will need to do some more tests to rule out other health conditions before they confirm you have MGUS.  

These further tests are usually ordered by a haematologist and may include: 

• Blood tests
• Urine (wee) tests
• Imaging (scans) tests
• Bone marrow aspiration and trephine biopsy (BMAT)

You read more about these on our Understanding your tests webpage.

How is MGUS managed? 

Current guidelines recommend that MGUS should be actively monitored, but not treated. This is because most people who have MGUS remain well and never develop any symptoms or problems related to it.  

Because a small number of people with MGUS may progress to a more serious condition like myeloma, it’s important to keep an eye on your MGUS, catching any changes early. This way, if you do need treatment, it can be started as soon as needed.  

Monitoring usually involves blood and/or urine tests to track your level of paraprotein or free light chains. 

Progression from MGUS to myeloma

Each year, about 1% (1 in 100) people with MGUS will slowly progress to develop myeloma, or another serious condition such as chronic lymphocytic leukaemia (CLL), non-Hodgkin lymphoma, or AL amyloidosis. 

At the moment, there is no test to predict who will develop myeloma and who will remain stable. Research is continuing to find the causes of progression, which may involve cell changes at a genetic level. 

MGUS progresses to myeloma when there is an increase of paraprotein in your blood and/or an increase of plasma cells in your bone marrow.  

If MGUS does progress, it happens in stages, with a stage in-between MGUS and active myeloma that’s called smouldering myeloma.   

The image below gives a visual guide to the differences between MGUS, smouldering myeloma, and active myeloma.

What are the signs that my MGUS might be progressing? 

Let your doctor know as soon as you notice any symptoms that are new or getting worse – don’t wait for your next blood test or appointment.  

Contact your doctor if you notice:  

• an unexpected broken bone (from only a small or unknown injury) 
• unexplained pain, especially in your back or ribs  
• unexplained bruising or bleeding  
• feeling tired, light-headed or breathless  
• tingling or numbness in your hands or feet 
• losing weight without trying  
• frequent infections or infections that don’t get better easily 
• feeling less healthy overall.  

In your blood or urine tests, your doctor will be looking for: 

• increased calcium levels  
• reduced kidney function  
• anaemia (low red blood cells) 
• increasing paraprotein or light chain levels

Living with MGUS

We understand that being diagnosed with MGUS can be unsettling and cause anxiety. It’s normal to worry about having a health condition that you are not having active treatment for and has a (very small) chance of progressing to something more serious. People with MGUS tell us that they are often most anxious when they are first diagnosed and then each time as they are waiting for the results of their monitoring tests. 

It’s important to remember that most people with MGUS never develop a serious health condition. The regular monitoring from your doctor means that any changes will be found early, helping them to take any action as soon as needed. 

Here are some ideas for finding support and staying positive:

• Talk to someone: Share your feelings with a trusted friend, family member, or your doctor. See the last page of this infosheet for Myeloma Australia support services.
• Focus on what you can control: Living a healthy lifestyle — like eating well, staying active, and prioritising your sleep — can boost both your physical and mental wellbeing.
• Take it one step at a time: Try not to let the ‘what ifs’ take over. Stay present and focus on the people and activities that bring you joy. If you ever feel anxious or overwhelmed, don’t hesitate to reach out to your treating team or our Specialist Myeloma Nurses for support. They’re here to help you every step of the way

My husband has been a constant source of support and comes to all my appointments. It helps having another person there to listen to and process everything being said. I also found reading up on MGUS helped me feel like I had a better understanding of the condition.

– Divya, South Australia