Multiple Myeloma

MGUS, Indolent Myeloma and Multiple Myeloma Staging

Multiple myeloma often begins to develop in the form of a benign condition known as monoclonal gammopathy of undetermined significance (MGUS). In time, some people with MGUS go on to develop a slowly progressing form of myeloma with minimal symptoms, known as indolent or smoldering myeloma, which may be considered the first stage of multiple myeloma.

People with MGUS have an abnormal protein antibody known as the M protein, indicating the presence of small quantities of abnormal plasma cells in the bone marrow. However, the abnormal plasma cells do not form tumors or cell masses, and individuals with MGUS do not have other evidence of myeloma, such as low numbers of red blood cells or bone damage. People with MGUS have one percent per year chance of ultimately progressing to multiple myeloma or lymphoma. The higher the number of abnormal plasma cells in bone marrow, and the higher the level of the M protein, the higher the chances someone with MGUS will progress to multiple myeloma or lymphoma.

Researchers have been studying the genetic characteristics of abnormal plasma cells in MGUS patients and have found that the genes in these plasma cells are more similar to myeloma cells than to normal plasma cells. This finding suggests that these cells may be pre-cancerous.

People diagnosed with smoldering myeloma have higher levels of M proteins in their blood and more abnormal plasma cells in their bone marrow than those with MGUS. However, they remain asymptomatic, that is, they do not yet have physical symptoms of multiple myeloma, such as recurrent infections or anemia. Most people with smoldering myeloma ultimately develop multiple myeloma.

Stages of Multiple Myeloma

Once a diagnosis of multiple myeloma is made, doctors sometimes classify the disease into stages. An important distinction is between asymptomatic patients without signs of organ development and those in whom the disease is symptomatic and associated with injury to organs such as the kidney. Asymptomatic patients are usually referred to as having smoldering myeloma and are followed without therapy. Symptomatic patients are always treated. Staging is a way to describe where the cancer is located, whether it has spread to different parts of the body and if it has affected the function of organs such as the kidneys.

Doctors determine the stage of the disease with blood counts of red and white cells, measurements of M proteins in blood and urine, calcium levels in the blood, blood levels of beta-2-microglobulin (a protein that plays a role in the immune system), and blood levels of albumin (a protein made in the liver that can indicate kidney function or damage). According to the commonly used International Staging System, multiple myeloma can be classified into three stages.

Table 1. Table 1. Stages of Multiple Myeloma