ConditionBlood & immune system
Monoclonal Gammopathy
A monoclonal gammopathy means that a single group (clone) of plasma cells is making an abnormal antibody protein, called an M-protein or paraprotein, that shows up in blood or urine tests. The most common form is MGUS (monoclonal gammopathy of undetermined significance), found in about 3% of people over 50. MGUS causes no symptoms and is not cancer, but it carries a risk of about 1% a year of turning into multiple myeloma or a related disease, so it is monitored with periodic blood tests.
Also called: Paraproteinemia, M-protein, MGUS (monoclonal gammopathy of undetermined significance), plasma cell dyscrasia
At a glance
- What it is
- An abnormal antibody protein made by a clone of plasma cells.
- Most common type
- MGUS, a harmless-looking precursor state in about 3% of adults over 50.
- Risk
- About 1% a year progress to myeloma, Waldenström macroglobulinemia, AL amyloidosis or lymphoma.
- Tests
- Serum protein electrophoresis, immunofixation, free light chains, blood count, calcium and kidney function.
- Management
- No treatment for MGUS; regular monitoring, with treatment only if a related disease develops.
When to get help
See a doctor within a day or two
- New bone pain, especially in the back, or a fracture after minimal injury
- Rapidly worsening tiredness, breathlessness or pale skin
- Reduced urine, foamy urine, or swelling of the legs
- Confusion, excessive thirst, constipation or vomiting (possible high calcium)
- Frequent or severe infections
Book a routine appointment
- A monoclonal protein found on a blood test
- Numbness, tingling or weakness in the feet that is gradually spreading
- Unexplained weight loss, night sweats or enlarged lymph nodes
- Missing a scheduled MGUS follow-up blood test
What a monoclonal gammopathy is
Plasma cells are white blood cells in the bone marrow that make antibodies (immunoglobulins). Normally, many different plasma cells make many different antibodies (polyclonal). In a monoclonal gammopathy, one clone of plasma cells multiplies and makes identical copies of one antibody or part of an antibody (a light chain). This shows up as a sharp "spike" on a protein electrophoresis test.
The M-protein can be IgG (most common), IgA, IgM, or only light chains (kappa or lambda).
Types of monoclonal gammopathy
| Condition | What defines it | Need for treatment |
|---|---|---|
| MGUS | M-protein under 3 g/dL, fewer than 10% plasma cells in the marrow, no organ damage | No; monitoring only |
| Light-chain MGUS | Abnormal free light chain ratio, no heavy chain, no organ damage | No; monitoring |
| Smoldering myeloma | M-protein 3 g/dL or more or 10 to 59% marrow plasma cells, no organ damage | Monitoring; treatment in high-risk cases in some centers |
| Multiple myeloma | Clonal plasma cells with organ damage (anemia, high calcium, kidney injury, bone lesions) or high-risk markers | Yes |
| Waldenström macroglobulinemia | IgM M-protein with lymphoma cells in the marrow | When symptomatic |
| AL amyloidosis | Light chains form deposits damaging the heart, kidneys, nerves or other organs | Yes |
| Monoclonal gammopathy of clinical significance | A small clone causing organ damage, such as kidney disease (MGRS) or neuropathy | Often yes |
Causes and risk factors
The cause of MGUS is not fully understood. Risk increases with:
- age: rare under 40; about 3% over 50 and 5% over 70
- male sex
- Black ancestry: about twice the rate of white people
- family history of MGUS or myeloma
- some exposures: possibly pesticides, Agent Orange and radiation
Symptoms
MGUS itself causes no symptoms. It is usually found by chance when blood tests are done to investigate something else, such as high protein levels, anemia, kidney problems or neuropathy.
Symptoms suggest progression or a related condition:
- bone pain or fractures, especially in the spine
- tiredness and breathlessness from anemia
- frequent infections
- kidney problems
- symptoms of high calcium: thirst, confusion, constipation
- numbness or tingling in the feet (paraproteinemic neuropathy)
- swelling, breathlessness or an enlarged tongue in AL amyloidosis
Diagnosis
- Serum protein electrophoresis (SPEP): detects and measures the M-protein
- Immunofixation: identifies the type of M-protein
- Serum free light chains: measures kappa and lambda light chains and their ratio
- Blood count, calcium, kidney function
- Urine protein electrophoresis in some cases
- Bone marrow biopsy and imaging (low-dose whole-body CT, PET-CT or MRI) when the M-protein is higher, non-IgG or the free light chain ratio is abnormal, or if there are symptoms
Risk stratification
Doctors estimate the risk that MGUS will progress using three features:
- M-protein of 1.5 g/dL or more
- non-IgG type (IgA or IgM)
- abnormal free light chain ratio
People with none of these (low-risk MGUS) have a very low lifetime risk of progression, while those with all three have a much higher risk.
Follow-up
- Low-risk MGUS: repeat blood tests about 6 months after diagnosis, then every 2 to 3 years or if symptoms develop. Some very low-risk older adults may stop routine monitoring.
- Intermediate and high-risk MGUS: blood tests at 6 months, then yearly.
- Smoldering myeloma: more frequent monitoring, typically every 3 to 6 months.
Report new symptoms promptly between appointments.
Treatment
MGUS does not need treatment. Treatment begins if it progresses to myeloma, Waldenström macroglobulinemia, amyloidosis or lymphoma, or if the M-protein causes organ damage (such as kidney disease or neuropathy). Bone health may be checked, because MGUS is associated with a slightly higher risk of osteoporosis and fractures.
Outlook
Most people with MGUS never develop a cancer and live normal lives. The average risk of progression is about 1% a year, and this risk does not disappear with time, which is why lifelong monitoring is usually recommended.
Frequently asked questions
What is a monoclonal gammopathy?
A monoclonal gammopathy is the presence of an abnormal antibody protein, called an M-protein, in the blood or urine. It is produced by a single clone of plasma cells. The most common form, MGUS, is not cancer but needs monitoring.
Is MGUS cancer?
No. MGUS is a precancerous condition. It causes no symptoms or organ damage. About 1% of people with MGUS each year develop multiple myeloma or a related blood cancer, so regular blood tests are recommended.
What are the chances MGUS turns into myeloma?
On average, about 1% of people with MGUS progress each year. The risk is lower for people with a small IgG M-protein and a normal free light chain ratio, and higher with a larger M-protein, IgA or IgM type, or an abnormal ratio.
How often should MGUS be monitored?
For low-risk MGUS, blood tests are usually repeated after 6 months, then every 2 to 3 years. Higher-risk MGUS is checked about every year. Smoldering myeloma needs more frequent tests. See your doctor sooner if symptoms appear.
Can MGUS go away?
MGUS usually persists for life, although the M-protein level can fluctuate. In some cases, especially when found during an infection or another illness, a small transient M-protein can disappear. Most people simply continue monitoring.
Sources
This guide was written from current patient and clinical guidance, including:
- International Myeloma Working Group: Criteria for the diagnosis of multiple myeloma and related disorders
- Mayo Clinic Proceedings: Risk stratification of MGUS (Rajkumar, Kyle and colleagues)
- National Cancer Institute: Plasma cell neoplasms (PDQ)
- American Society of Hematology: Monoclonal gammopathy
- MedlinePlus: Monoclonal gammopathy of undetermined significance