Multiple Myeloma

Monoclonal gammopathy of undetermined significance (MGUS)

Multiple myeloma often starts as a condition known as monoclonal gammopathy of undetermined significance (MGUS). MGUS begins in the bone marrow, the part of the body where blood cells are produced. People with MGUS have an abnormal protein antibody, monoclonal immunoglobulin (M protein), which is made in the bone marrow (see Figure 1). The presence of the M protein in the blood or urine indicates a small amount of abnormal plasma cells in the bone marrow. These abnormal cells do not form tumors or cell masses, and people with MGUS do not have any other signs of myeloma.

Figure 1

MGUS usually does not cause symptoms, but some people may have a rash or nerve problems such as numbness or tingling. It is most often detected in blood and urine tests ordered for another reason. If the M protein is present in these samples, other tests, such as imaging studies and biopsies, can be done to diagnose MGUS. People with MGUS often get a thorough evaluation to rule out multiple myeloma.

MGUS can develop into multiple myeloma or another malignant plasma cell disease, such as lymphoma or amyloidosis. A higher number of abnormal plasma cells in the bone marrow means a higher level of the M protein, increasing the risk that MGUS will progress to multiple myeloma. The genes of abnormal plasma cells in people with MGUS are more like those of myeloma cells than those of normal plasma cells.

If you have MGUS, your doctor will consider various factors to predict your risk of disease progression. These may include:

  • The size and type of M proteins in your blood.
  • The amount of free light chains (another protein) in your blood.
  • Your age at diagnosis. Your risk of progression increases the longer you’ve had MGUS.

MGUS may develop into a form of myeloma with few symptoms, known as smoldering (or indolent) myeloma. People with smoldering myeloma have a higher level of the M protein in their blood and more abnormal plasma cells in their bone marrow than people with MGUS. Despite this higher level, smoldering myeloma does not cause other signs or symptoms of multiple myeloma. Multiple myeloma eventually develops in most people with smoldering myeloma.

MGUS does not cause any problems and does not require treatment. However, people with the M protein should be monitored by a doctor during the first year after diagnosis for signs of progression. Such monitoring is called watchful waiting. Multiple myeloma can develop without causing any symptoms, so close monitoring is crucial for early detection.

The only two known precursors to multiple myeloma are MGUS and smoldering myeloma. Most cases of multiple myeloma are preceded by MGUS, but it is unknown whether MGUS is always present before diagnosis. At this time, no treatments exist for MGUS, and no preventive treatments can keep MGUS from progressing to myeloma. People with MGUS should not be treated until multiple myeloma is present.

Preventive treatments to delay smoldering myeloma from progressing to multiple myeloma are being studied in clinical trials. Ask your doctor if you may be a candidate for a clinical trial.

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