Monoclonal gammopathy of undetermined significance (MGUS) is a blood disorder where an abnormal protein, called M protein, is found in your blood. MGUS isn’t cancer, but in some people it can be an early sign of multiple myeloma and other blood disorders.

Being diagnosed with MGUS can be scary. Learning more about the condition and how it differs from multiple myeloma can help you understand what to expect.

What Is MGUS?

MGUS is a blood disorder that affects plasma cells — the same blood cells that become cancerous in multiple myeloma. Plasma cells are a type of white blood cell (WBC) that make immune proteins called antibodies. Antibodies, also known as immunoglobulin (Ig), help your immune system fight harmful invaders, like bacteria and viruses.

In MGUS, your bone marrow produces abnormal plasma cells that make M protein instead of normal antibodies. M protein, also called monoclonal protein, can cause organ damage if levels are high. However, M protein doesn’t usually cause problems in people with MGUS.

How Common Is MGUS?

MGUS is more common than multiple myeloma. About 2 percent to 3 percent of people over the age of 50 have MGUS. This prevalence increases to about 5 percent in those over age 70. In contrast, multiple myeloma is far less common, with an estimated 100,000 individuals diagnosed in the United States​​.

The risk factors for developing MGUS and multiple myeloma are similar. According to Mayo Clinic, they include:

• Being older
• Being male
• Being Black
• Having a family history of MGUS or multiple myeloma

MGUS Usually Doesn’t Cause Symptoms

People with MGUS usually don’t experience any symptoms. However, symptoms of MGUS can occur if M protein builds up and damages parts of the body. For example, if M protein damages your nerves, it can lead to peripheral neuropathy. Symptoms of peripheral neuropathy may include numbness, tingling, or weakness.

Some people with MGUS also have an increased risk of developing other conditions, such as infections, heart disease, or kidney disease.

People with multiple myeloma have high numbers of abnormal plasma cells that have become cancerous. These cancerous cells are also called myeloma cells. When you have too many myeloma cells, they crowd out other blood cells that your body needs to function. This can lead to symptoms related to anemia (low red blood cells), a weakened immune system, and bleeding. More myeloma cells also means more M protein. High levels of M protein in people with multiple myeloma can damage organs, including the kidneys.

Signs and symptoms of multiple myeloma include:

• High blood calcium levels
• Kidney problems
• Anemia
• Bone lesions and fractures

Because people with MGUS have much lower levels of abnormal plasma cells and M protein than those with multiple myeloma, they don’t usually have the signs and symptoms characteristic of multiple myeloma.

MGUS Is Often Diagnosed After Routine Blood Tests

Since MGUS doesn’t cause any symptoms, it’s often found after routine blood tests for other health conditions. If your health care provider suspects you have MGUS, they may refer you to a hematologist (blood disease specialist) for further evaluation.

Many of the same tests used to diagnose multiple myeloma are also used to diagnose MGUS. These tests include:

• Blood and urine tests — These check for the amount and type of M protein in your blood and urine, helping to detect abnormalities associated with MGUS or multiple myeloma.
• Imaging tests — If you have bone pain, imaging tests such as X-rays, CT scans, or MRIs may be recommended to identify bone problems.
• Bone marrow biopsy — This involves using a hollow needle to extract a sample of bone marrow for testing. It is typically performed if there is concern about a high risk of developing another blood disorder or to confirm a diagnosis of multiple myeloma.

Imaging tests and bone marrow tests are necessary for diagnosing multiple myeloma.

Most MGUS Doesn’t Require Treatment

In most people with MGUS, increased levels of M protein levels don’t cause any problems and don’t require treatment. However, some people may be at a higher risk for bone problems related to MGUS. In such cases, your health care provider may recommend medications to improve bone density and prevent bone fractures or other complications.

Before progressing to multiple myeloma, MGUS may advance to an intermediate stage called smoldering multiple myeloma (SMM). SMM is a precancerous condition where abnormal plasma cells are more active than in MGUS but have not yet caused organ damage or other symptoms associated with multiple myeloma. People with SMM often don’t need treatment right away, but they require close monitoring. If either MGUS or SMM progresses to full-blown multiple myeloma, treatment such as medications, chemotherapy, radiation, or a bone marrow transplant may be necessary.

MGUS Monitoring

If treatment isn’t needed right away, your health care team will monitor you closely for any changes. After you are diagnosed with MGUS, you will likely have follow-up appointments every six to 12 months to check for signs of a more serious disease. Most people with MGUS don’t need any additional treatment for many years after diagnosis.

In addition to regular follow-ups with your health care provider, it’s important to watch for any new symptoms that could suggest that MGUS is progressing. Symptoms to watch for include:

• Bone pain
• Nerve pain
• Tiredness
• Loss of appetite
• Unexplained weight loss
• Night sweats
• Unexplained bleeding or bruising
• Swollen lymph nodes
• Pain or swelling in your abdomen (stomach)

How Often Does MGUS Become Myeloma?

About 20 percent of people with MGUS will eventually develop multiple myeloma. There’s a 1 percent risk per year that MGUS will turn into multiple myeloma or a related blood condition, such as:

• Light chain amyloidosis — A condition where abnormal proteins build up in the body
• Waldenstrӧm’s macroglobulinemia — A type of non-Hodgkin lymphoma
• Chronic lymphoproliferative disorders — A group of blood cancers, including chronic lymphocytic leukemia (CLL)

Everyone with a multiple myeloma diagnosis has had MGUS at some point. Before MGUS turns into multiple myeloma, it typically progresses to SMM.

Researchers are still unsure why some people progress to multiple myeloma while others don’t. One member of MyMyelomaTeam shared, “I went from MGUS to SMM in no time. They weren't surprised at all, because I was having serious issues with fractures, and joints having to be replaced.”

For some people, the disease progresses more slowly. Another MyMyelomaTeam member shared, “My journey from MGUS to SMM was slow, but from SMM to multiple myeloma was aggressive.”

Risk Factors for Progressing to Multiple Myeloma

You may have a higher risk of developing a more serious condition if you have the following risk factors:

• M protein levels higher than 15 grams per liter
• M protein type IgA, IgM, or IgD (instead of the more common IgG)
• Abnormal free light chain ratio in your blood

A health care professional can assess your risk of progression based on how many of these risk factors you have. Here’s how the risk levels are categorized:

• Low-risk — No risk factors
• Low-intermediate risk — One risk factor
• High-intermediate risk — Two risk factors
• High-risk — Three risk factors

One MyMyelomaTeam member shared, “I was diagnosed with MGUS in 2020. In 2023, I progressed to SMM. I have high risk markers that made me progress quickly.”

Can You Prevent Multiple Myeloma With MGUS?

It’s still unknown why some people with MGUS develop multiple myeloma. Without knowing what triggers MGUS progression, it’s also not possible to stop MGUS from progressing. However, your health care provider can help you stay your healthiest while living with MGUS. Regular checkups and ongoing monitoring are a good place to start.

Researchers are studying how and why MGUS and other blood conditions develop. If you’re interested in helping with this research, ask your health care provider about joining a clinical trial. For example, the Pcrowd study is an ongoing clinical trial looking at how MGUS turns into cancer.

Talk With Others Who Understand

MyMyelomaTeam is the social network for people with multiple myeloma and their loved ones. On MyMyelomaTeam, more than 26,000 members come together to ask questions, give advice, and share their stories with others who understand life with multiple myeloma.

Are you living with MGUS? Were you diagnosed with MGUS before you were diagnosed with multiple myeloma? Share your experiences in the comments below, or start a conversation by posting on your Activities page.