Smoldering myeloma overview

Last updated Oct. 29, 2025, by Lindsey Shapiro, PhD
Fact-checked by Ana de Barros, PhD

Smoldering multiple myeloma (SMM) is a precancerous plasma cell disorder that can sometimes progress to the rare blood cancer multiple myeloma.

Plasma cells are white blood cells that produce antibodies to help the body fight infections. They’re created in the bone marrow, the spongy center of bones where most blood cells are made.

In multiple myeloma, or active myeloma, plasma cells grow out of control in the bone marrow and crowd out other healthy blood cells. They produce an atypical antibody called M protein that contributes to organ damage.

SMM is an asymptomatic precursor to this blood cancer, in which myeloma cells have started to accumulate, but not to the point where they’re causing organ damage.

Some patients with SMM never develop active myeloma, but many do. It is critical that people with SMM are carefully monitored so that progression to multiple myeloma can be promptly detected and properly managed.

Symptoms and diagnosis

SMM is typically asymptomatic because the abnormal plasma cells that are accumulating have not yet started to cause the tissue damage that drives myeloma symptoms. This can make it particularly challenging to diagnose SMM, which is commonly discovered by chance in medical tests done for other reasons.

Diagnosing SMM and ruling out active multiple myeloma involves several tests:

Blood and urine samples will be collected to measure M protein and look for other abnormalities suggesting progression to active myeloma.
A bone marrow biopsy evaluates the percentage of abnormal plasma cells in the bone marrow and looks for myeloma-related genetic abnormalities in plasma cells.
Imaging tests monitor bone health and look for evidence of myeloma-related organ or bone damage.

A formal SMM diagnosis is reached when the following diagnostic criteria are met:

Blood M protein concentrations must be at least 3 grams per deciliter (g/dL) and/or 10%-60% of bone marrow cells are plasma cells.
There is no evidence of myeloma-defining events, defined as clinical signs and symptoms of myeloma-related organ damage or lab indicators suggesting progression to cancer is essentially soon inevitable.

If SMM is diagnosed, doctors assess how likely it is to progress to active myeloma and continue lifelong monitoring for any signs of progression over time.

Differences from MGUS

If M protein levels and plasma cell percentages are elevated, but don’t reach the SMM criteria, it could mean a person has another asymptomatic precursor condition called monoclonal gammopathy of undetermined significance (MGUS).

SMM is between MGUS and active myeloma on a spectrum of related plasma cell disorders. Each is associated with a risk of progression to multiple myeloma, although the risk is higher with SMM.

The two disorders, both lacking in myeloma symptoms, can be distinguished based on the levels of M protein and plasma cell percentages.

Causes and risk factors

In multiple myeloma, plasma cells acquire genetic abnormalities that cause them to grow out of control. Such mutations may also be observed in the abnormal plasma cells of people with SMM.

The exact cause of these plasma cell abnormalities is not known. The risk factors for SMM overlap with those for active multiple myeloma and include:

older age
male sex
Black race
exposure to certain chemicals, like pesticides and herbicides
family history of MGUS or myeloma
an MGUS diagnosis

Ongoing research is aimed at better understanding the mechanisms by which smoldering myeloma becomes active multiple myeloma. It’s thought to involve a process by which abnormal plasma cells continue to acquire more genetic mutations and adapt in ways that further promote their growth.

Treatment and management approaches

SMM management typically involves a watch-and-wait type of strategy in which individuals are carefully monitored for signs of disease progression.

However, this approach has been challenged in recent years with the recognition that early intervention may help improve long-term outcomes, especially for patients with a high risk of progression.

For people with high-risk smoldering myeloma who are very likely to develop active myeloma, a doctor may recommend certain steps:

Patients may be urged to start myeloma treatments, such as immunomodulatory drugs (IMiDs). Clinical trials have demonstrated that the IMiD Revlimid (lenalidomide), with or without dexamethasone, can slow the progression to myeloma-associated organ damage in people with SMM.
Entry into a clinical trial may be recommended. While clinical trials offer access to potentially disease-slowing interventions, they are experimental approaches and there is no guarantee they will be effective.

A person’s risk of disease progression can change over time, and as such, a physician may recommend a shift from active surveillance to treatment while continuing to monitor the disease.

Disease progression

There is no definitive way to prevent SMM from becoming myeloma, and the rate at which this could happen varies.

About three-quarters of people with SMM will develop active myeloma at some point in their lives. The risk is highest in the first five years after diagnosis, when approximately 10% of SMM patients develop active myeloma per year. The risk drops to 3% during each of the next five years, and further declines to 1% per year — similar to what’s seen in MGUS — after the first decade.

A person’s individual risk of disease progression may be determined with the commonly used Mayo Clinic 2/20/20 Model, which places individuals into a risk group based on three key factors:

blood M protein levels higher than 2 g/dL
bone marrow plasma cell percentage greater than 20%
blood immunoglobulin light chain (antibody fragment) ratio higher than 20

Based on the presence of those factors, a person is grouped into one of three categories with an increasing risk of two-year disease progression:

low (zero risk factors), with a 6% progression risk
intermediate (one risk factor), with an 18% progression risk
high (two or three risk factors), with a 44% progression risk

The presence of certain genetic abnormalities can also influence the risk of progression.

There are other models that stratify the risk in different ways. A person’s healthcare team will use the individual’s risk score to determine what type of monitoring or treatment is needed.

SMM monitoring should be done by a hematologist-oncologist, a clinician who specializes in blood disorders and cancer. Such monitoring will involve blood and urine tests, with bone marrow biopsies and imaging as needed. These will be done every four to six months in the first year, and may become less frequent over time if a person does not show any signs of disease progression.

Lifestyle and wellness considerations

There are no lifestyle changes that can definitively cure SMM or prevent its progression to myeloma, but some research suggests that a healthy, plant-based diet high in fiber may be beneficial. Engaging in regular physical activity is also important for maintaining overall health.

Individuals with SMM should always talk with their healthcare team before making any changes to their activity, diet or nutrition regimens to make sure they are safe in their individual case.

Receiving an SMM diagnosis can take an emotional toll, leading to stress, anxiety, and fear. Thus, it is important to find mental health support, such as:

counseling or therapy
support groups
online communities and resources, including Rare Cancer News

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