What Is Smoldering Myeloma?

Risk Factors, Symptoms, Diagnosis and Treatment

Smoldering myeloma, or smoldering multiple myeloma (SMM), is a rare pre-cancerous condition involving abnormal proteins and increased plasma cells in the bone marrow. It doesn't have symptoms but can cause severe complications.

In some cases, SMM progresses to a rare blood cancer called multiple myeloma (MM). Anyone diagnosed with SMM should be evaluated for their risk of developing MM.

This article looks at possible signs, symptoms, and complications, the risk of progression, SMM causes and risk factors, how it's diagnosed and treated, and how to cope with the condition.

Older woman getting blood drawn by a phlebotomist
Alex Raths / Getty Images

Why "Smoldering"?

SMM is called "smoldering" because it worsens slowly over time.

Smoldering Myeloma Symptoms, Signs, Complications

Smoldering myeloma doesn't have any symptoms. It's tied to the absence of multiple myeloma symptoms, which include:

However, SMM does have signs (in the form of lab results) as well as potentially serious complications.

Signs of SMM

The abnormal protein tied to SMM is called M protein. Produced by malignant (cancerous) plasma cells, M protein is an abnormal antibody (immune-system cells that attack dangerous germs.)

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
  • A high urine level of Bence Jones protein (a protein made by plasma cells)

Complications of SMM

While it lacks earlier symptoms, over time, high levels of M protein in your blood can cause severe complications, such as:

Proper treatment can lower your chances of developing these complications.

Your Risk of Progression

People with SMM are at risk of developing multiple myeloma, but 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 per year

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.

While treatment can lower your risk of progression, it can also cause severe side effects. So, only those at high risk should be treated. 

Historically, healthcare providers have struggled to identify who's most at-risk. Now, they use 2020 guidelines for determining that. It relies on three blood tests: 

  • M protein level in the blood = 2g/dL or higher
  • Bone marrow plasma cells = 20% or more
  • Free light chain (an immune system that protein that functions as an antibody) ratio = 20 or higher

This is sometimes called the 2/20/20 risk stratification or the 3 risk factor model.

Healthcare providers may also look for genetic abnormalities believed to play a role in MM. This is called the 4 risk factor model.

Under these models, your risk is determined by how many factors are positive. It determines your risk of progressing to multiple myeloma within two years.

3 RISK FACTOR MODEL # 2-YEAR MM RISK
Low  0 6.2% 
Intermediate  17.9% 
High  2-3  44.2% 
4 RISK FACTOR MODEL    
Low  6%
Low-intermediate  22.8% 
Intermediate  45.5% 
High  3-4  63.1% 

If you're in the high-risk category, you're a candidate for immediate treatment aimed at slowing the progression of the disease and keeping you symptom-free.

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: Cis males have slightly higher rates than cis females.
  • Obesity: Increases your risk of both conditions.

Diagnosis and Monitoring

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 problem.

Once you're diagnosed with SMM, it’s important to visit your healthcare provider approximately every three months for ongoing blood and urine tests. This helps the provider continue to evaluate your risk of progression. 

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 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.

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 typically involves:

  • Chemotherapy drugs: Slow the progression from SMM to multiple myeloma. Examples are Revlimid (lenalidomide) and dexamethasone.
  • Monoclonal antibodies: Newer drugs that help your immune system fight cancer. Examples are Darzalex (daratumumab), Sarclisa (isatuximab-irfc), and Empliciti (elotuzumab). 

Ongoing research aims to determine what early treatments are most effective at preventing SMM progression.

Coping

Being diagnosed with smoldering myeloma can be emotionally challenging. It's natural to fear that this pre-cancerous disorder will progress to cancer, especially if you're at higher risk.

If you're having trouble coping with your fears or suspect you're 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.

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 tumors, and an impaired immune system.

Healthcare providers asses your risk of SMM progressing to multiple myeloma based on results lab tests. People at high risk generally start treatment to prevent or delay multiple myeloma.

SMM appears to be caused by a mix of genetics, age, race, sex, and obesity. It's diagnosed with blood, urine, and imaging tests plus bone marrow biopsy. Treatment involves chemotherapy drugs or newer anti-cancer medication.

If you're having trouble coping with your diagnosis, consider mental health counseling and/or a support group.

5 Sources
Verywell Health uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read our editorial process to learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.
  1. National Institutes of Health, National Cancer Institute. Drug shows promise in slowing progression of smoldering myeloma to cancer.

  2. Multiple Myeloma Research Foundation. Early treatment of smoldering multiple myeloma.

  3. Muchtar E, Kumar SK, Magen H, Gertz MA. Diagnosis and management of smoldering multiple myeloma: the razor’s edge between clonality and cancer. Leukemia and Lymphoma. 2018 Feb;59(2):288-299. doi:10.1080/10428194.2017.1334124

  4. Mateos MV, Kumar S, Dimopoulos MA, et al. International Myeloma Working Group risk stratification model for smoldering multiple myeloma (SMM)Blood Cancer J. 2020;10(10):102. Published 2020 Oct 16. doi:10.1038/s41408-020-00366-3

  5. Musto P, La Rocca F. Monoclonal antibodies in newly diagnosed and smoldering multiple myeloma: an updated review of current clinical evidenceExpert Rev Hematol. 2020;13(5):501-517. doi:10.1080/17474086.2020.1753502

Additional Reading

By Sherry Christiansen
Sherry Christiansen is a medical writer with a healthcare background. She has worked in the hospital setting and collaborated on Alzheimer's research.