Smoldering multiple myeloma (SMM) is a precancerous condition. SMM is preceded by a related condition called monoclonal gammopathy of unknown significance (MGUS), and it can lead to active multiple myeloma, a type of blood cancer. Doctors believe that precancerous conditions such as SMM always come before a person develops multiple myeloma, although they are not always diagnosed.

What Is Smoldering Multiple Myeloma?

SMM and multiple myeloma are both diseases that affect plasma cells. Plasma cells are a type of white blood cell. They make immunoglobulins (antibodies), proteins that fight infection. Plasma cells live inside soft tissue called bone marrow, found inside certain bones.

People with plasma cell disorders have too many abnormal plasma cells. These cells make high levels of identical proteins called M protein, also known as monoclonal protein or M spike. MGUS is the mildest type of plasma cell disorder. SMM is the intermediate level of plasma cell disorders between MGUS and myeloma. Both MGUS and SMM are benign (noncancerous) conditions that don’t cause any symptoms. They may turn into multiple myeloma, the most severe type of plasma cell disorder.

People with SMM have higher levels of plasma cells and M protein than people with MGUS — but lower levels than people with full-blown multiple myeloma. In some cases, SMM may be like a more severe form of MGUS. In other cases, doctors think of SMM as multiple myeloma that hasn’t yet caused symptoms or organ damage.

When Does SMM Turn Into Multiple Myeloma?

People with smoldering myeloma have a higher chance of developing active multiple myeloma. Risk of progression is highest right after a person is first diagnosed with SMM, and decreases over time. For example:

• For the first five years after being diagnosed with SMM, about 10 percent of people develop multiple myeloma each year.
• Five to 10 years after being diagnosed with SMM, 3 percent of people develop multiple myeloma each year.
• Ten years or more after SMM diagnosis, about 1 percent of people develop multiple myeloma each year.

Certain risk factors increase the chances that SMM will progress to full-blown multiple myeloma, including having the following:

• Plasma cells with certain gene changes
• High numbers of plasma cells in the bone marrow
• High levels of M protein
• M protein levels that increase over time
• M protein made from IgA heavy chain, rather than IgG
• Bone lesions (bone damage or abnormalities) that can appear on X-rays

Signs and Symptoms of Smoldering Multiple Myeloma

SMM is asymptomatic, which means it doesn’t cause any symptoms. However, people with SMM may have disease signs. Symptoms are abnormalities felt by the person experiencing them. Pain and nausea are examples of symptoms. On the other hand, signs are issues that can be noticed by another person or measured with a test, whether or not they cause symptoms. Examples of signs include a rash or high body temperature.

People with SMM have signs of disease — too many plasma cells or too much M protein — but they don’t feel them. Symptoms including bone pain, nausea, trouble thinking, or tiredness may be indicators of active multiple myeloma.

SMM Diagnosis

Doctors usually first suspect smoldering multiple myeloma when tests show that a person’s blood contains more proteins than usual. Additional tests can identify signs of SMM.

Doctors use several different tests to measure levels of M protein. These tests usually require either a blood sample or a urine sample. Tests to measure levels or types of M protein include:

• Serum protein electrophoresis
• Urine protein electrophoresis
• Immunofixation electrophoresis
• Quantitative immunoglobulin testing
• Serum-free light-chain assay

If tests show increased levels of M protein, doctors may recommend bone marrow tests. One such test is a bone marrow aspiration, in which a sample of fluid is removed from the bone marrow. Another is a bone marrow biopsy, in which doctors collect a small sample of cells. In order to perform these tests, doctors use a long needle to withdraw samples, usually from the hip bone. Doctors use bone marrow tests to measure how many plasma cells are in the bone marrow. This information can help make the diagnosis or determine prognosis.

Increased levels of M protein or plasma cells is a sign of plasma cell disease. Additional tests are needed to know whether the condition is active multiple myeloma or a precancerous condition such as MGUS or SMM. These tests include blood tests to measure whether the organs are working correctly and imaging tests to look for tumors or bone damage. If a doctor finds certain abnormalities, they may give a diagnosis of full-blown multiple myeloma. These abnormalities can include signs of organ damage, including :

• Hypercalcemia (high calcium levels)
• Renal dysfunction (kidney failure)
• Anemia (low levels of red blood cells)
• Thrombocytopenia (decreased platelets)
• Bone lesions

Certain biomarkers of myeloma may also result in a multiple myeloma diagnosis, including:

• Very high levels of plasma cells
• High levels of M protein
• Multiple tumors

Treatments for Smoldering Multiple Myeloma

In the past, doctors would recommend an approach called “watchful waiting” or “watch and wait” for SMM. This approach is used for other conditions and entails having regular follow-up visits and testing to monitor a condition’s progress. If SMM does progress to multiple myeloma, frequent testing can catch cancer early. The advantage of watchful waiting is that people with a condition can avoid treatment side effects.

Some people with SMM take bisphosphonates. These drugs strengthen the bones and protect against bone damage. Bisphosphonates include Aredia (pamidronate), Xgeva (denosumab), and Zometa (zoledronic acid).

Recently, evidence has been accumulating that earlier treatment may improve the prognosis of SMM. Early treatment may be particularly helpful for people who have high-risk smoldering myeloma and are more likely to develop multiple myeloma. Some clinical trials have shown that drugs such as Revlimid (lenalidomide) and low-dose Decadron (dexamethasone) may reduce chances of developing myeloma for people with higher risk SMM.

Talk With Others Who Understand

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