Smoldering Multiple Myeloma (SMM): What It Is, How It's Diagnosed, and What Comes Next — Complete Guide
Updated: 2 days ago
Medically reviewed by Dr. Baraa Alnahhal, MD · Last reviewed: September 2026
TL;DR: Smoldering multiple myeloma (SMM) is a plasma cell condition in which changed plasma cells build up in the bone marrow and produce monoclonal (M) protein, causing no symptoms and no organ damage. It sits between MGUS and active multiple myeloma. Risk of progression ranges from 6% in 2 years (low-risk) to 44% (high-risk) under the 20/2/20 model. Most people are actively monitored; adults with high-risk SMM may be offered daratumumab, which reduced the risk of progression or death by 51% in a 390-person trial.
Quick Answer
Smoldering multiple myeloma (SMM) is a condition in which changed plasma cells build up in the bone marrow and produce atypical monoclonal protein (M protein) — but cause no symptoms and no organ damage. It is more advanced than MGUS yet not active multiple myeloma. It is diagnosed by blood or urine M protein levels and bone marrow plasma cell percentages, then risk-stratified with the 20/2/20 model. Treatment is either active monitoring or, for high-risk adults, daratumumab, which cut the risk of progression or death by 51% in a clinical trial [1] [2].
Editorial note: This guide is based on source-only reporting from major medical institutions, including Mayo Clinic (updated August 15, 2026), the NCCN, the FDA, and peer-reviewed journals. It is intended for education only and is not a substitute for professional medical advice.
What is smoldering multiple myeloma?
Smoldering multiple myeloma (SMM), also called smoldering myeloma, is a condition in which changed plasma cells build up in the bone marrow. Plasma cells are white blood cells that help fight infection. The changed cells make protein that is not typical. It is called monoclonal protein, or M protein [1].
SMM is more advanced than the plasma cell condition known as monoclonal gammopathy of undetermined significance (MGUS) but it is not active multiple myeloma. SMM does not cause the organ damage or other changes that define active multiple myeloma [1].
SMM is sometimes described as a very early form of blood cancer. It also may be described as a condition that comes before active multiple myeloma [1].
Where SMM sits on the myeloma spectrum
Stage | M protein | Bone marrow plasma cells | Organ damage? |
MGUS | Below 3 g/dL | Less than 10% | No myeloma-defining events [2] |
Smoldering multiple myeloma | At least 3 g/dL in blood, or at least 500 mg/24 h in urine | 10% to less than 60% | No myeloma-defining events or AL amyloidosis [2] |
Active multiple myeloma | Any level meeting criteria | Any level meeting criteria | Yes — CRAB events or high-risk findings [2] |
Some people have low-risk SMM that may remain stable for years. Others have high-risk SMM and are more likely to develop active multiple myeloma. People with high-risk SMM have a greater chance of developing active multiple myeloma, and some healthcare professionals describe high-risk SMM as an early form of multiple myeloma that has not caused symptoms [1].
What are the symptoms of smoldering multiple myeloma?
Smoldering multiple myeloma causes no symptoms. There are no recognized early-stage or late-stage SMM symptoms [1].
This is a key point: SMM is typically discovered incidentally, not because of how a person feels. It is usually found when a blood test done for another reason shows M protein, or during follow-up for MGUS [2].
Symptoms that may signal progression
Symptoms that appear during monitoring may be due to another condition. But they also may mean that SMM has worsened — also called progressed — to active multiple myeloma. Possible symptoms include [1]:
New or ongoing bone pain, especially in the back, ribs or hips.
A broken bone that happens with little or no injury.
Fatigue, weakness or shortness of breath.
Frequent or serious infections.
Nausea, constipation, confusion or thirst that is not usual.
Passing less urine or having swelling in the legs.
New numbness, tingling or weakness.
Bone lesions — areas of damaged or changed bone — do not occur with SMM. If myeloma causes a bone lesion, the condition may be diagnosed as active multiple myeloma [1]. A rash is not a typical symptom of SMM; tell your care team about a new rash, especially if it develops after starting treatment. Neuropathy (numbness, tingling or burning pain) is not typical of SMM either [1].
When to seek care
Contact your care team right away if you have a new symptom, even if it seems mild. Symptoms that need medical review include lasting or worsening bone pain, a possible broken bone, increasing fatigue or shortness of breath, frequent infections or a fever, changes in urination or new swelling, numbness or tingling, and confusion, unusual thirst, nausea or constipation [1].
Seek emergency care for severe back pain with sudden leg weakness or numbness, trouble walking, or loss of bladder or bowel function. These symptoms may be caused by pressure on the spinal cord [1].
What causes smoldering multiple myeloma?
The exact cause of smoldering multiple myeloma is not known.
SMM develops when one group of plasma cells grows more than expected and produces M protein. Many people first have monoclonal gammopathy of undetermined significance (MGUS), a less advanced plasma cell condition. MGUS may remain stable. Or it may progress to SMM or active multiple myeloma [1].
Researchers continue to study the genetic and biological changes that allow plasma cells to grow and SMM progress [1].
What are the risk factors?
The factors that cause a person to develop smoldering multiple myeloma are not fully understood. Factors linked with SMM include [1]:
MGUS. SMM may develop during follow-up for MGUS.
Older age. SMM is most often diagnosed in older adults.
Sex at birth. SMM happens more often in men.
Most people with these factors do not develop SMM. There is no known lifestyle change that reliably prevents it [1].
Context for scale: MGUS affects roughly 3 to 5 percent of Americans over age 50 [3], yet only a fraction of people with MGUS ever progress to SMM. SMM itself remains rare — population screening found it in about 0.53 percent of people aged 40 or older [4], and clinically detected cases rose from 6.9 to 11.3 per 100,000 people between 2011 and 2021 [5].
How likely is SMM to progress?
The main complication of smoldering multiple myeloma is that it may worsen, also called progress, to active multiple myeloma. Progression means the plasma cells have increased or changed enough to cause organ damage or other findings that define active disease [1].
Active multiple myeloma can cause bone damage or broken bones, anemia (too few red blood cells), kidney damage, hypercalcemia (high blood calcium), and frequent or serious infections [1].
A 2026 systematic review in eClinicalMedicine provides the best available group-level estimates [1]:
Risk group | Progression within 2 years | Progression within 10 years |
All risk groups (systematic review) | ~23% | ~60% |
High-risk SMM | ~45% | ~86% |
These numbers describe groups of people. They cannot predict whether or when SMM will progress in one person [1].
Two conditions SMM must be distinguished from
Amyloidosis. SMM and amyloidosis are different plasma cell conditions. A diagnosis of SMM requires that there be no evidence of light-chain amyloidosis (AL amyloidosis). If testing finds AL amyloidosis, the diagnosis and treatment approach are different [1].
Myelodysplastic syndromes. SMM and myelodysplastic syndromes are different conditions that affect bone marrow. Current evidence does not show that SMM causes myelodysplastic syndromes. Low blood cell counts can have many causes, so they need medical evaluation [1].
How is smoldering multiple myeloma diagnosed?
There is no routine screening recommendation for people at average risk of SMM. The goals of testing are to confirm that a plasma cell condition is present, distinguish SMM from MGUS and active multiple myeloma, check for organ damage, and estimate the risk of progression [2].
Diagnostic criteria
SMM is diagnosed when testing finds one or both of the following [2]:
M protein level in the blood of at least 3 grams per deciliter, or M protein in the urine of at least 500 milligrams in 24 hours.
Changed plasma cells making up 10% to less than 60% of the cells in the bone marrow.
For a diagnosis of SMM, you also must not have light-chain amyloidosis or a myeloma-defining event. Myeloma-defining events include the organ damage grouped under the term CRAB [2]:
Letter | Meaning | What it indicates |
C | High calcium | Blood calcium above the diagnostic threshold [2] |
R | Renal (kidney) | Kidney function below the diagnostic threshold [2] |
A | Anemia | Hemoglobin below the diagnostic threshold due to myeloma [2] |
B | Bone | One or more bone lesions caused by myeloma [2] |
Other results that may mean SMM has become active multiple myeloma include plasma cells making up 60% or more of the bone marrow; a free light-chain ratio of 100 or higher with the involved light chain at least 100 mg/L; or an MRI showing more than one area of changed bone marrow, each at least 5 millimeters [2]. Your care team interprets these results together — one result alone may not be enough [2].
The tests involved
Your care team may use the following tests [2]:
Blood tests. A complete blood count measures blood cells. Other tests measure calcium, kidney function, M protein, immunoglobulins and serum free light chains.
Urine tests. A 24-hour urinalysis may measure M protein and show how the plasma cell condition is affecting the kidneys.
Bone marrow testing. A bone marrow biopsy measures plasma cells and allows testing of their chromosomes and genes. The procedure may cause short-term soreness, bruising or bleeding.
Imaging. A whole-body low-dose CT scan, MRI or positron emission tomography (PET) scan may look for bone lesions or areas of changed bone marrow.
Repeat testing. Blood, urine and imaging tests are repeated over time. Changes in results may be as important as a single measurement.
Risk stratification: the 20/2/20 model
Your healthcare team uses a risk assessment to estimate how likely SMM is to change to active multiple myeloma. This is called progression. The risk is different for each person and may change as test results differ over time [2].
The 20/2/20 model (also called the 2/20/20 model) uses three test results [2]:
Finding | Threshold |
Bone marrow plasma cells | More than 20% of the marrow [2] |
M protein in blood | More than 2 g/dL [2] |
Free light-chain ratio | Involved-to-uninvolved ratio more than 20 [2] |
The number of these findings determines the risk group:
Risk group | Number of findings | Risk of progression within 2 years |
Low risk | None | 6% [2] |
Intermediate risk | One | 18% [2] |
High risk | Two or three | 44% [2] |
High risk does not mean that SMM will become active multiple myeloma. These percentages are estimates based on groups of people. Genetic changes in plasma cells and trends over time in M protein, light chains, hemoglobin and kidney function help your care team refine the risk estimate [2].
How is smoldering multiple myeloma treated?
Treatment depends on the risk of progression, test results, age, overall health and personal preferences. Active monitoring and early treatment may both be reasonable options for some people with high-risk SMM [2].
Active monitoring
Active monitoring means having regular visits and tests without starting medicine right away. It also is called active surveillance or observation [2].
Monitoring may include a physical exam and review of symptoms, blood and urine tests, imaging when needed, a repeat bone marrow biopsy in some situations, and reassessment of the risk category. Visits often occur every few months at first, and your care team decides the schedule based on your results and risk level [2].
Active monitoring avoids treatment side effects when treatment may not yet be needed. It is important to keep every follow-up appointment because SMM can progress without obvious symptoms [2].
Treatment for high-risk SMM
A medicine containing daratumumab may be given to adults with high-risk SMM. The medicine is injected under the skin. Daratumumab is a monoclonal antibody that attaches to a protein called CD38 on plasma cells [2].
The key evidence comes from a 390-person study of high-risk SMM [2]:
Daratumumab reduced the risk of progression or death by 51% compared with active monitoring.
At 5 years, 63.1% of people receiving daratumumab were alive without progression, versus 40.8% with active monitoring.
Possible risks include reactions during or after an injection, infections, low levels of certain white blood cells, thrombocytopenia (low platelet count), high blood pressure, and effects on blood-matching tests before a transfusion [2]. This treatment is approved for adults with high-risk SMM and is not approved for other SMM risk groups [2].
Can smoldering multiple myeloma be cured?
SMM may remain stable for many years, but it does not usually go away on its own. Treatment for high-risk SMM aims to delay or prevent progression to active multiple myeloma. Researchers are studying whether early treatment can provide long-term control or cure SMM in some people [2].
What lifestyle and coping steps help?
No diet, supplement or lifestyle change has been shown to cure SMM or reliably keep it from progressing. Healthy habits can support your overall health and help you stay as healthy as possible if you need treatment [2].
Consider these steps [2]: go to all monitoring and imaging appointments; tell your care team about new symptoms; stay physically active at a safe level; eat a varied, balanced diet unless your care team recommends restrictions; ask how to protect your bones and reduce your risk of falls; review vitamins, herbs and other supplements with your care team; and ask which vaccinations are appropriate for you.
Avoid making major diet changes or taking supplements based on claims that they can eliminate M protein. Evidence does not support these claims [2].
Living with a condition that may or may not get worse can cause worry. It may help to ask your care team to explain your risk category in plain language, keep copies of your laboratory and imaging reports, write down questions between visits, talk with a mental health professional if worry affects sleep or daily activities, and connect with a support group for people with plasma cell conditions [2].
Conclusion
Smoldering multiple myeloma occupies an unusual middle ground: it is more advanced than MGUS, yet it is not active multiple myeloma, and — critically — it causes no symptoms and no organ damage. For most people, the right approach is disciplined active monitoring, with visits every few months, because SMM can progress quietly.
The picture is changing, though. For adults with high-risk SMM — defined by the 20/2/20 model — daratumumab is now an approved option backed by a 390-person trial showing a 51% reduction in the risk of progression or death.
If your blood tests ever show M protein or you've been told you have MGUS, don't wait for symptoms — ask your doctor about a referral to a hematologist, learn your risk category in plain language, and keep every monitoring appointment. Early detection of progression is what protects bone, kidney, and blood health. For personalized decisions, talk with a qualified health professional.
For education only; consult a qualified health professional for medical advice.
Frequently Asked Questions (FAQ)
What is smoldering multiple myeloma?
Smoldering multiple myeloma (SMM) is a condition in which changed plasma cells build up in the bone marrow and produce atypical monoclonal protein (M protein). It is more advanced than MGUS but not active multiple myeloma, because it causes no organ damage [1].
Does smoldering multiple myeloma have symptoms?
No. SMM causes no symptoms, and there are no recognized early- or late-stage SMM symptoms. It is usually found incidentally on blood tests or during MGUS follow-up. New symptoms during monitoring may signal progression to active myeloma and should be reported right away [1].
How is SMM diagnosed?
SMM is diagnosed when testing shows M protein of at least 3 g/dL in blood (or at least 500 mg/24 h in urine) and/or changed plasma cells making up 10% to less than 60% of bone marrow — with no myeloma-defining events and no light-chain amyloidosis. Diagnosis involves blood tests, a 24-hour urine test, bone marrow biopsy, and imaging [2].
What is the difference between MGUS, SMM, and active multiple myeloma?
MGUS has M protein below 3 g/dL, bone marrow plasma cells below 10%, and no organ damage. SMM meets the higher thresholds but still has no organ damage. Active multiple myeloma involves myeloma-defining events (CRAB: high calcium, kidney issues, anemia, bone lesions) or high-risk test findings [2].
What does the 20/2/20 model mean?
The 20/2/20 model stratifies SMM risk using three findings: bone marrow plasma cells over 20%, blood M protein over 2 g/dL, and a free light-chain ratio over 20. Zero findings means low risk (6% progression in 2 years), one means intermediate (18%), and two or three mean high risk (44%) [2].
Is smoldering multiple myeloma cancer?
SMM is sometimes described as a very early form of blood cancer or a condition that comes before active multiple myeloma. Because it involves changed plasma cells but no organ damage, some clinicians describe high-risk SMM as an early form of multiple myeloma that has not caused symptoms [1].
What treatment options exist for SMM?
Options are active monitoring (regular visits, blood and urine tests, imaging) or, for adults with high-risk SMM, daratumumab injected under the skin. In a 390-person trial, daratumumab reduced the risk of progression or death by 51% versus monitoring, with 63.1% progression-free at 5 years versus 40.8% [2].
Can smoldering multiple myeloma be cured?
SMM may remain stable for many years but does not usually go away on its own. Treatment for high-risk SMM aims to delay or prevent progression to active multiple myeloma. Researchers are studying whether early treatment can provide long-term control or cure in some people [2].
References
Mayo Clinic Staff. "Smoldering Multiple Myeloma — Symptoms and causes." Mayo Clinic, updated August 15, 2026. https://www.mayoclinic.org/diseases-conditions/smoldering-multiple-myeloma/symptoms-causes/syc-20605178
Mayo Clinic Staff. "Smoldering Multiple Myeloma — Diagnosis and treatment." Mayo Clinic, updated August 15, 2026. https://www.mayoclinic.org/diseases-conditions/smoldering-multiple-myeloma/diagnosis-treatment/drc-20605191
Kyle RA, Larson DR, Therneau TM, et al. "Prevalence of Monoclonal Gammopathy of Undetermined Significance." New England Journal of Medicine, 2006;354:1362–1369. https://www.nejm.org/doi/full/10.1056/NEJMoa054494
"Incidence and prevalence of clinically detected smoldering multiple myeloma" (iStopMM screening study). PMC/ASH, 2025. https://pmc.ncbi.nlm.nih.gov/articles/PMC12397400/
"Incidence and Prevalence of Clinically Detected Smoldering Multiple Myeloma." Blood (ASH), Supplement 1, 2024. https://ashpublications.org/blood/article/144/Supplement%201/1912/532978/
National Comprehensive Cancer Network. "Multiple Myeloma" (Version 5.2026). NCCN Clinical Practice Guidelines in Oncology. https://www.nccn.org/professionals/physician_gls/pdf/myeloma.pdf
Dimopoulos MA, et al. "Daratumumab or Active Monitoring for High-Risk Smoldering Multiple Myeloma." New England Journal of Medicine, 2025. https://doi.org/10.1056/NEJMoa2409029
U.S. Food and Drug Administration. "FDA approves daratumumab and hyaluronidase-fihj for high-risk smoldering multiple myeloma." FDA. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-daratumumab-and-hyaluronidase-fihj-high-risk-smoldering-multiple-myeloma
Ludwig H, et al. "Temporal trends in progression risk in smoldering myeloma: A systematic review." eClinicalMedicine, 2026. https://doi.org/10.1016/j.eclinm.2025.103750
National Cancer Institute. "Cancer Stat Facts: Myeloma." SEER Program. https://seer.cancer.gov/statfacts/html/mulmy.html
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