ConditionBlood & immune system
MGUS (Monoclonal Gammopathy of Undetermined Significance)
MGUS (monoclonal gammopathy of undetermined significance) is a common, symptom-free condition in which a small group of plasma cells in the bone marrow makes an abnormal antibody called a monoclonal protein (M-protein). It is usually found by chance on a blood test. MGUS is not cancer, but it carries a small risk, about 1% per year, of progressing to multiple myeloma or a related blood cancer. Most people never progress, and management is regular monitoring rather than treatment.
Also called: Monoclonal gammopathy of undetermined significance, monoclonal gammopathy, M-protein, paraproteinemia
At a glance
- What it is
- A small amount of abnormal monoclonal protein in the blood from a group of plasma cells, without cancer.
- How common
- About 3% of people over 50 and more with age. More common in men and Black Americans.
- Symptoms
- None from MGUS itself.
- Progression risk
- About 1% per year to myeloma, Waldenström macroglobulinemia, AL amyloidosis or lymphoma.
- Management
- Risk assessment, then periodic blood (and sometimes urine) tests. No treatment unless complications arise.
When to get help
See a doctor within a day or two
- New bone pain, especially in the back or ribs, or a fracture after minor injury
- Increasing tiredness, breathlessness or pale skin (possible anemia)
- Frequent or serious infections
- Foamy urine, leg swelling or reduced urine output
- Excessive thirst, confusion or constipation (possible high calcium)
Book a routine appointment
- Numbness, tingling or burning in the feet (possible MGUS-related neuropathy)
- Scheduled follow-up blood tests: do not skip them
- Unexplained weight loss or night sweats
What MGUS is
Plasma cells are white blood cells that make antibodies. Normally, many different plasma cells make many different antibodies. In MGUS, one clone of plasma cells makes a single type of antibody, which shows up as a spike (M-spike) on a blood test called serum protein electrophoresis.
MGUS is called "of undetermined significance" because, at the time of diagnosis, it is not causing harm and it is unclear whether it ever will.
Who gets it
- prevalence rises with age: about 3% over age 50 and more in people over 70
- more common in men
- about twice as common in Black Americans
- more common in first-degree relatives of people with MGUS or myeloma
- linked with obesity in some studies
How MGUS is found
Usually by chance, when blood tests are done for something else, such as high total protein, kidney problems, anemia or neuropathy.
Tests used:
- serum protein electrophoresis (SPEP) and immunofixation: detect and identify the M-protein
- serum free light chains (kappa and lambda) and their ratio
- complete blood count, calcium and kidney function
- urine protein tests in some cases
Diagnostic criteria (IgG or IgA MGUS)
MGUS is diagnosed when:
- the M-protein is less than 30 g/L (3 g/dL)
- clonal plasma cells in the bone marrow are under 10% (if a bone marrow test is done)
- there is no sign of organ damage related to plasma cells, remembered as CRAB: high Calcium, Renal (kidney) failure, Anemia or Bone lesions
| Condition | M-protein | Bone marrow plasma cells | Organ damage |
|---|---|---|---|
| MGUS | Under 3 g/dL | Under 10% | None |
| Smoldering myeloma | 3 g/dL or more, or | 10% to 59% | None |
| Multiple myeloma | Usually present | 10% or more (or plasmacytoma) | CRAB features or other defining events |
Types of MGUS
- non-IgM MGUS (IgG, IgA): can progress to multiple myeloma
- IgM MGUS: can progress to Waldenström macroglobulinemia or lymphoma
- light-chain MGUS: only light chains are abnormal. Can progress to light-chain myeloma or AL amyloidosis
Risk of progression
The overall risk is about 1% per year and does not disappear with time. The Mayo Clinic risk model uses three factors:
- M-protein of 1.5 g/dL or more
- a type other than IgG (IgA or IgM)
- an abnormal free light chain ratio
| Risk factors present | Approximate 20-year progression risk |
|---|---|
| 0 (low risk) | About 5% |
| 1 | About 21% |
| 2 | About 37% |
| 3 (high risk) | About 58% |
Many people with low-risk MGUS will never progress during their lifetime.
Monitoring
- low-risk MGUS: repeat blood tests at 6 months, then every 2 to 3 years or only if symptoms develop, according to many guidelines
- intermediate or high risk: a bone marrow test and imaging may be done at diagnosis, then blood tests every 6 to 12 months
- seek review sooner if new symptoms appear
Conditions linked to MGUS even without progression
The M-protein can sometimes cause problems itself, known as monoclonal gammopathy of clinical significance:
- peripheral neuropathy, especially with IgM
- kidney damage (monoclonal gammopathy of renal significance)
- skin conditions
- increased risk of osteoporosis, fractures, blood clots and infections
These may need treatment even though myeloma is not present.
Treatment
MGUS itself does not need treatment. Care focuses on:
- monitoring for progression
- bone health: vitamin D, calcium, weight-bearing exercise, and bone density testing where appropriate
- vaccinations
- treating any MGUS-related complications
Research into early intervention is ongoing, but treatment of MGUS outside trials is not recommended.
Frequently asked questions
What is MGUS?
MGUS is a condition in which plasma cells make a small amount of an abnormal antibody (M-protein). It causes no symptoms and is not cancer, but it carries a small risk of progressing to multiple myeloma or related blood cancers.
Does MGUS turn into cancer?
Usually not. The risk is about 1% per year. Many people, especially those with low-risk MGUS, never develop myeloma or a related condition. Regular blood tests watch for early signs of change.
What are the symptoms of MGUS?
MGUS itself does not cause symptoms. It is usually found by chance. Rarely, the abnormal protein causes nerve damage with numbness or tingling in the feet, or kidney problems.
How often should MGUS be monitored?
Typically, blood tests are repeated 6 months after diagnosis. Low-risk MGUS may then be checked every 2 to 3 years, while higher-risk MGUS is checked every 6 to 12 months. Report new bone pain, tiredness or infections promptly.
Can MGUS go away?
MGUS rarely disappears completely, though M-protein levels can fluctuate. Very small or transient monoclonal proteins sometimes appear after infections or transplants and then resolve. Most people have MGUS lifelong without it causing harm.
Sources
This guide was written from current patient and clinical guidance, including:
- International Myeloma Working Group (IMWG): Criteria for the diagnosis of multiple myeloma and related disorders
- Mayo Clinic: Monoclonal gammopathy of undetermined significance
- National Cancer Institute: Plasma cell neoplasms treatment (PDQ)
- International Myeloma Foundation: MGUS
- American Society of Hematology: Blood cancers