Smoldering Multiple Myeloma (SMM): Symptoms and Causes

Smoldering multiple myeloma (SMM) is a precancerous condition affecting white blood cells, called plasma cells, in the bone marrow. It can turn into multiple myeloma, a form of blood cancer that can damage vital organs.

About 50% of people with SMM develop multiple myeloma within five years. However, SMM doesn’t always progress to multiple myeloma.

People with SMM usually don’t have symptoms. You and your healthcare provider may discover you have SMM through routine blood tests that reveal elevated monoclonal protein (M-protein) levels. After diagnosis, SMM treatment approaches vary, depending on your risk of progression to multiple myeloma.

Smoldering multiple myeloma does not generally cause symptoms.

However, SMM may develop into multiple myeloma, and symptoms can develop if the condition progresses. If SMM progresses to multiple myeloma, symptoms can include: 

• Frequent infections 
• Bone pain, especially in the ribs and back 
• Weakness and fatigue 
• Easy bruising and bleeding
• Loss of appetite
• Weight loss 

SMM occurs when abnormal plasma cells build up in your bone marrow. Plasma cells are white blood cells that produce antibodies, the proteins that help your body fight infection.

Research suggests that sudden genetic changes likely play a role in the development of SMM. Genetic changes in plasma cells may change how these cells function, causing them to multiply rapidly and produce abnormal proteins called monoclonal antibodies (M-proteins)—which don’t contribute to immune defense. 

Experts aren’t sure why these genetic mutations occur, but some evidence suggests environmental and lifestyle factors play a role.

Risk Factors

Although the exact cause of SMM is not fully understood, certain risk factors are associated with a higher likelihood of developing the condition. These include: 

• Age: The risk of SMM increases with age, and most people are 50-70 years old at diagnosis.
• Sex: People assigned male at birth have a higher likelihood of developing SMM than people assigned female at birth.
• Race: SMM is more common in Black people than other races, though evidence suggests Black people may have a slightly lower risk of their SMM progressing to multiple myeloma than white people do.
• Environmental exposures: Exposure to environmental toxins, such as herbicides, microplastics, and benzene, may increase the risk of SMM.
• Family history: A family history of multiple myeloma may increase the risk of developing SMM. 

Because smoldering multiple myeloma usually causes no symptoms, your healthcare provider may discover it by chance. Signs of SMM may show up during routine blood or urine tests or when your provider is evaluating or monitoring other conditions you have.

These tests will reveal markers of SMM if you have it. Markers include M-protein blood levels of 3 grams per deciliter or higher and M-protein urine levels of 500 milligrams or more.

To confirm a diagnosis of SMM, your healthcare provider may order additional testing, including bone marrow biopsy and imaging tests.

A bone marrow biopsy involves taking a sample of bone marrow to examine under a microscope and measure the percentage of abnormal plasma cells. In SMM, 10-60% of plasma cells are abnormal.

Imaging tests, such as magnetic resonance imaging (MRI), computed tomography (CT) scan, and positron emission tomography (PET) scans, provide detailed images of your bones and internal organs. Your provider may use imaging tests to check for bone damage or other damage to internal organs that could indicate progression to active multiple myeloma.

The main goal of treating SMM is to prevent or delay progression to multiple myeloma. Depending on your risk of progressing to multiple myeloma, your healthcare provider may recommend a watchful waiting approach or medications to slow or prevent disease progression. 

Watch and Wait Approach

Because there’s a lack of symptoms, immediate treatment isn’t always necessary. Healthcare providers may instead take a watchful waiting approach that involves regular testing to monitor your health. These tests may include: 

• Blood tests: Your provider may use blood tests to measure your M-protein levels every 4-6 months the first year after diagnosis. If your SMM remains stable after a year, your healthcare provider may recommend blood tests every 6-12 months. 
• Urine tests: You may need to undergo a 24-hour urine collection 2-3 months after initial diagnosis. This test requires you to collect samples of all your urine over a 24-hour period.
• Imaging tests: Regular MRIs of the spine and pelvis can help your provider look for bone changes that may indicate progression to multiple myeloma. 
• Bone marrow biopsies: Periodic bone marrow biopsies can help your provider assess the percentage of abnormal plasma cells in your bone marrow. 

Medications 

If your healthcare provider determines you’re at a high risk of developing multiple myeloma, they may recommend you begin treatments to help reduce the number of abnormal plasma cells in your bone marrow and slow disease progression. These treatments may include immunomodulating drugs and monoclonal antibodies. 

Immunomodulating drugs like Revlimid (lenalidomide) may slow disease progression or prevent the development of multiple myeloma by boosting your body’s natural immune ability to kill cancer cells. In clinical trials, 91% of people receiving Revlimid therapy did not progress to multiple myeloma in the three years after treatment.

Your healthcare provider may also prescribe monoclonal antibodies, which target and destroy abnormal plasma cells. Medications such as Darzalex (daratumumab), Sarclisa (isatuximab), and Empliciti (elotuzumab) may slow or prevent disease progression. 

Clinical Trials 

People with high-risk SMM may consider participating in clinical trials. Clinical trials for SMM focus on testing new therapies or new ways to implement existing treatments to help slow or prevent disease progression.

Talk to your healthcare provider if you’re interested in participating in a clinical trial. They can work with you to assess your eligibility for clinical trials and closely monitor your progress throughout the trial.

There are no proven ways to prevent smoldering multiple myeloma yet. If you have SMM, certain lifestyle habits may lower your risk of progressing to active multiple myeloma. These include: 

• Regular monitoring: It’s important to attend all scheduled checkups and routine blood tests, imaging tests, and bone marrow assessments to help ensure early detection of any disease progression.
• A nutrient-dense diet: Consuming a diet rich in fruits, vegetables, plant-based proteins, and whole grains and reducing your intake of red meats, processed foods, dairy products, and high-sugar foods and beverages may help reduce systemic (body-wide) inflammation and the risk of active multiple myeloma.
• Avoidance of infections: Staying up to date with vaccinations and practicing proper hygiene can help lower your risk of viral and bacterial infections, which may help reduce stress on your immune system and prevent disease progression. 

People with smoldering multiple myeloma have a higher risk of developing certain conditions, including multiple myeloma and amyloidosis.

SMM could be a step before multiple myeloma, a blood cancer where abnormal plasma cells grow uncontrollably and affect bone, kidney, and immune health. The risk of progressing to multiple myeloma is about 10% per year.

Some people with SMM may develop amyloidosis, where abnormal proteins called amyloids gather in their tissues and organs. This condition is due to the same abnormal plasma cells that produce excess M-proteins in SMM.

When living with smoldering multiple myeloma, it’s natural to experience worry, anxiety, and uncertainty about your health. Joining support groups for people with SMM allows you to connect with others who understand what you’re going through, which can help boost your quality of life. 

About 10% of people with SMM progress to multiple myeloma each year. People at lower risk may remain stable with their SMM diagnosis forever, never progressing to multiple myeloma.

Along with attending regular checkups and continuous monitoring, healthy lifestyle adjustments can help keep your immune system strong and lower the risk of disease progression. Your healthcare provider can make further recommendations tailored to your needs and lifestyle.