What Is Smoldering Myeloma?
A rare, pre-cancerous condition affecting the bone marrow
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Medically reviewed by Doru Paul, MD
Smoldering myeloma is a rare, pre-cancerous condition involving abnormal proteins and increased plasma cells in the bone marrow. It is called "smoldering" because it doesn't produce symptoms, but also doesn't resolve. It slowly worsens over time, eventually leading to severe complications.
Though sometimes called smoldering multiple myeloma (SMM), this condition is not the same as multiple myeloma (MM), a rare blood cancer. However, in some cases, SMM can turn into MM. Anyone diagnosed with SMM should be evaluated for this risk.
This article looks at possible signs, causes, and complications of smoldering myeloma. It also discusses the risk of progression, treatments, and how to cope.
Smoldering Myeloma Symptoms
Smoldering myeloma is an asymptomatic condition, meaning you will not notice any signs or symptoms that hint you have it. The main sign of SMM—the presence of a myeloma (M) protein in the blood—is only identified with bloodwork.
People usually learn they have SMM when a routine blood test comes back indicating multiple myeloma. (The M-protein is an abnormal antibody produced by cancerous plasma cells.)
Multiple myeloma may not cause symptoms early on, so this test result can come as a surprise. When MM does cause symptoms, they can include frequent infections, bone pain, kidney problems, and anemia, which might also prompt testing that reveals the diagnosis.
Related:How Your Immune System Works
Complications
While it lacks earlier symptoms, over time, high levels of M-protein in your blood can cause severe complications, such as:
Bone disorders: If SMM progresses to multiple myeloma, there is a significant risk of bone damage. About 85% of people with MM have a type of bone disorder such as osteolytic lesions or osteoporosis (bone loss). The spine, pelvis, and rib cage are the most common areas affected by MM-related disorders.
Kidney damage: Having too much M-protein can overload the kidneys. The issue is further complicated by the excess calcium build-up that occurs in people with multiple myeloma. The kidneys are then unable to properly filter waste from the blood, which can lead to kidney failure.
Nerve damage: Peripheral neuropathy, nerve damage that causes numbness or tingling in the feet or hands, is a common complication associated with M-protein.
Compromised immune system: While this condition leads to high antibody levels, the antibodies produced don't work right and overtake healthy cells. This leads to an impaired immune system and frequent infections.
Proper treatment can lower your chances of developing these complications.
Causes and Risk Factors
No one really knows what causes smoldering myeloma or multiple myeloma. Experts suspect several causal and risk factors are at play:
Genetics: Specific gene mutations may cause high levels of plasma cells.
Age: Diagnoses are most likely between the ages of 50 and 70.
Race: Black people have double the rates of white people.
Sex: Males have slightly higher rates than females.
Related:Multiple Myeloma in Black People
Diagnosis
Most of the time, smoldering myeloma is diagnosed accidentally, when abnormal lab tests show up during a routine physical or when your healthcare provider is investigating a different medical condition.
Lab findings for SMM may include:
M-protein blood levels of 3 grams per deciliter (g/dL) or higher
Plasma cells in the bone marrow that are 10% or higher but lower than 60%
A high level of Bence-Jones protein (a protein made by plasma cells) in urine
Part of the diagnostic of smoldering myeloma is also:
Absence of lytic lesions, anemia, hypercalcemia, and kidney impairment (end-organ damage) that can be attributed to the plasma cell proliferative disorder and the absence of biomarkers associated with near inevitable progression to end-organ damage (≥60 percent clonal plasma cells in the marrow; involved/uninvolved free light chain [FLC] ratio of ≥100 with involved FLC >100 mg/dL; or more than one focal bone lesion on magnetic resonance imaging [MRI]).
Risk of Progression
While people with smoldering myeloma are at risk of developing multiple myeloma, the risk drops over time:
Within five years after diagnosis: 50% of cases will progress to MM
Between five and 10 years after diagnosis: Another 15% of cases will progress to MM
After the 10-year mark: 1% of cases progress to MM
Determining your risk of multiple myeloma is important for treatment purposes. A 2017 study revealed evidence that early treatment of high-risk cases helped people live longer.
Those at low to intermediate risk of progression are not treated due to the potential for severe side effects.
If you are high-risk, you're a candidate for immediate treatment aimed at slowing the progression of the disease and keeping you symptom-free.
Determining Your Risk Level
To identify who's most at risk of smoldering myeloma progressing to multiple myeloma, healthcare providers rely on guidelines set out in the 3-risk-factor model, or 2/20/20 risk stratification.
Tests are done to check bone marrow plasma cells, M-protein levels, and free light chains—immune system proteins that function as antibodies.
One point is given for every result indicating an elevated risk of disease progression two years from diagnosis:
Blood Test | Result Indicating Elevated Risk |
Serum M-protein | > 2 g/dL |
Bone marrow plasma cells | > 20% |
Serum free light chain ratio | > 20 |
Points are interpreted as follows:
0 points: Low risk of progression
1 point: Intermediate risk of progression
2 to 3 points: High risk of progression
Healthcare providers may also use the 4-risk-factor model, which adds the presence of genetic abnormalities believed to play a role in MM into the equation. The scoring is similar:
0 points: Low risk of progression
1 point: Low-intermediate risk of progression
2 points: Intermediate risk of progression
3 to 4 points: High risk of progression
Your score in either of these models translates to the following risk of developing multiple myeloma two years after a smoldering myeloma diagnosis:
Risk Level | 2-Year MM Risk |
Low | 10% |
Intermediate | 26% |
High | 47% |
Risk Level | 2-Year MM Risk |
Low | 6% |
Low-intermediate | 22.8% |
Intermediate | 45.5% |
High | 63.1% |
Ongoing Monitoring of Smoldering Myeloma
Once you're diagnosed with SMM, you will continue to be monitored to see if the disease is progressing to MM. It's recommended that people with SMM be evaluated every four months, but those evaluations may be increased to every six months.
Diagnostic tests often used for ongoing observation of SMM may include:
Blood tests: These measure M-protein levels.
Urine tests: 24-hour urine collections are standard upon diagnosis and again two to three months later.
Bone marrow biopsy: This involves withdrawing cells from the bone marrow with a needle and examining them for myeloma cells.
Imaging tests (X-rays, PET scans, CT scans, or MRI): Upon diagnosis, these establish a baseline for your bones so your healthcare provider can spot abnormal changes down the road.
Smoldering Myeloma Treatment
Right now, multiple myeloma can't be cured, so prevention is paramount. That's why high-risk people with SMM should be treated.
Treatment of smoldering myeloma typically involves:
Chemotherapy drugs: These slow the progression from SMM to multiple myeloma. Examples include Revlimid (lenalidomide) and dexamethasone.
Monoclonal antibodies: These newer drugs help your immune system fight cancer. Examples include Darzalex (daratumumab), Sarclisa (isatuximab-irfc), and Empliciti (elotuzumab).
Ongoing research aims to determine what early treatments are most effective at preventing SMM progression.
Learn More:How Multiple Myeloma Is Treated
Coping With SMM
Being diagnosed with smoldering myeloma can be emotionally challenging. It's natural to fear that this pre-cancerous condition will progress to cancer, especially if you're at higher risk.
If you're having trouble coping with your fears or suspect you are clinically depressed, talk to your healthcare provider about mental health counseling.
It may also help to talk with friends and family or find a support group online or in your community. Your healthcare team may be able to recommend one, or you can check out the support group directories maintained by the International Myeloma Foundation and Multiple Myeloma Research Foundation.
Summary
SMM is a pre-cancerous condition that may progress to a blood cancer called multiple myeloma and cause serious health problems such as kidney damage, bone disorders, and an impaired immune system.
Healthcare providers determine your risk of SMM progressing to multiple myeloma based on the results of lab tests. People at high risk generally start treatment to prevent or delay multiple myeloma. This involves chemotherapy drugs or newer anti-cancer medication.
