Smoldering multiple myeloma (SMM) is a condition that affects plasma cells in the bone marrow. These are a type of white blood cell that help keep the body safe from infection.

SMM is a subdivision of multiple myeloma, which is a type of blood cancer. The name “smoldering” means that it typically worsens over time as it progresses, although someone with SMM may have no active symptoms. Often the only indications of SMM are an increase of plasma cells in the bone marrow and overproduction of an abnormal protein that builds up in the blood and urine.

SMM is a rare disorder. The American Cancer Society estimates that doctors will diagnose 34,920 cases of multiple myeloma in the United States in 2021. Although they do not have precise figures, scientists estimate that of these individuals, around 8–20% of people with multiple myeloma have SMM.

There is currently no cure for SMM. Doctors may treat high-risk individuals to slow down disease progression and help them remain symptom free.

This article looks at SMM. It covers how doctors may opt to treat the condition and a person’s outlook following a diagnosis of SMM.

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SMM is a condition that increases plasma cells in the bone marrow and alters specific proteins in the blood. It also goes by the name asymptomatic myeloma because most patients with SMM experience no symptoms.

Although it is not a type of cancer, it can progress to cancer. Those with SMM have a high risk of developing multiple myeloma, which is a type of cancer that influences plasma cells. These specialized cells are primarily located in the bone marrow and are an essential part of the immune system. They make antibodies that help the body attack and kill germs. When plasma cells become cancerous, instead of antibodies, they produce an abnormal protein called monoclonal protein (M-protein), or monoclonal immunoglobulin.

Having SMM does not mean that a person will go on to have multiple myeloma. In some cases, SMM progresses slowly and never results in multiple myeloma.

SMM is an asymptomatic disorder, meaning that it does not cause symptoms in most individuals. Because someone may have no symptoms, doctors may only diagnose SMM when they perform blood tests for other reasons.

While most individuals with SMM do not have any symptoms at first, they may develop symptoms if the condition progresses to multiple myeloma, including:

  • bone pain
  • brittle bones
  • fatigue (lack of energy) and weakness
  • infection
  • problems with balance
  • numbness or tingling in the hands and feet
  • confusion
  • dizziness
  • kidney problems

Doctors typically use either the Mayo Clinic model or the Spanish model to classify the risk of SMM progressing to multiple myeloma. People may be at low risk, intermediate risk, or high risk.

The Mayo Clinic model

The Mayo Clinic model looks at the level of M-proteins that abnormal cells produce, and proteins from the plasma cells called light chains.

These plasma cell proteins can be free light chains, or they can team with another form of protein called heavy chains to form antibodies. There are two types of serum-free light chains, and the Mayo Clinic model looks at the ratio between them. Depending on someone’s results, their SMM falls into one of three categories:

  • low-risk individuals with no risk factors
  • intermediate-risk individuals with one risk factor
  • high-risk individuals who have two to three risk factors

Some of the risk factors for the Mayo Clinic model include age, decreased hemoglobin level, creatinine level, and light-chain type.

The Spanish model

Unlike the Mayo Clinic model, the Spanish model looks only for high-risk individuals instead of categorizing them into different risk levels.

The Spanish model looks at the proportion of abnormal bone marrow plasma cells and then if someone has a noticeable reduction in specific antibodies.

Most individuals with SMM have no symptoms that lead to a diagnosis. If the individual feels well and has no concerning symptoms yet has M-protein in their blood, a doctor may perform additional testing to determine an SMM diagnosis.

If a doctor suspects someone has SMM, they may perform the following diagnostic tests:

  • complete blood count and blood smear
  • biochemical analysis of creatinine and calcium levels, beta 2-microglobulin, LDH, and albumin
  • protein studies of blood and urine
  • skeletal survey or X-rays of multiple bones
  • bone marrow aspirate
  • CT scan
  • MRI scan

There are no approved treatments for SMM. Because of this, most doctors follow a “watch and wait” approach, which involves closely monitoring someone for signs that their SMM is progressing to active multiple myeloma.

At follow-up visits, a doctor may request the following tests:

  • complete blood count
  • blood chemistry tests
  • protein electrophoresis
  • quantitative immunoglobulin test
  • urinalysis
  • serum-free light chain test

Recent research has found that early treatment with lenalidomide helped improve people’s overall survival. The drug is currently undergoing clinical trials. If doctors treat people who have no symptoms, the individual could needlessly experience the unpleasant and severe side effects of cancer treatment.

SMM is more common in women than in men and in African Americans than in Caucasians. Increasing age also affects the risk of SMM, as most people who have SMM are between the ages of 50 and 70 years.

While there is no known cause for SMM, some risk factors for progression to active myeloma include the number of abnormal plasma cells and paraprotein in the bone marrow.

The risk that smoldering multiple myeloma progresses to cancerous multiple myeloma is 50–60% during the first 5 years after someone receives their diagnosis. In some cases, SMM progresses so slowly that it never evolves into multiple myeloma.

If someone develops localized multiple myeloma, meaning they have a single tumor growing in or around the bone, their 5-year relative survival rate is 75%. This means they are 75% as likely as someone without localized multiple myeloma to live for 5 years after their diagnosis. If they have distant multiple myeloma, meaning they have several or numerous tumors, the rate drops to 53%.

SMM is a plasma cell disorder. If a person has SMM, it means they have an increased risk of developing multiple myeloma.

People often have no symptoms. But with SMM, the bone marrow plasma cells become abnormal and produce a protein called an M-protein. If someone has blood tests for another reason, the presence of this protein may be the first indication that they have SMM.

Most doctors do not treat SMM and instead monitor for any progression. This requires frequent checkups and testing. Around 50–60% of those with SMM develop multiple myeloma within 5 years of their diagnosis.