Multiple Myeloma


Once you’ve been diagnosed with multiple myeloma, the next step for doctors is to determine the stage of the disease. In this process, the results of your diagnostic testing are used to determine the extent of the cancer, develop an appropriate treatment plan and predict treatment outcomes.

Multiple myeloma can be staged using one of two staging systems: the Revised International Staging System (RISS) and the Durie-Salmon Staging System (see Tables 1 and 2).

Although both staging systems are composed of three stages, the stages do not mean the same thing. Many doctors may choose to use the RISS because it is more cost effective and uses a simpler test than the Durie-Salmon Staging System to stage myeloma.

The RISS distinguishes between the three stages using precise measurements that are based on the levels of three proteins in the blood.

  1. Albumin is a type of protein made by the liver. Your doctor may test this protein to determine how well your liver and kidneys are functioning. Low levels may indicate a more advanced myeloma.
  2. Beta-2-microglobulin is a protein malignant myeloma cells make. Your doctor may test this protein to stage and monitor the myeloma. High levels of this protein may indicate a more advanced myeloma.
  3. Lactate dehydrogenase (LDH) is a protein that helps cells convert sugar to energy. Your doctor may test this protein to determine if any tissue damage has occurred. High levels may indicate a more advanced myeloma.

The presence of genetic abnormalities is also considered through a process of evaluating cells called cytogenetics. One method called fluorescence in situ hybridization, or FISH, is used to look for abnormal cells which may be associated with a more advanced myeloma. Cytogenetic analysis may help you and your doctor determine the treatment plan most likely to be effective for you.

The Durie-Salmon Staging System is also used to stage multiple myeloma. This staging system measures the amount of abnormal plasma cells in the body to determine the size of the tumor. Four main factors determine the stage.

  1. Amount of M protein. The amount of abnormal protein that is in the blood or urine is measured. Large amounts may indicate the presence of a high number of malignant plasma cells.
  2. Calcium level. The destruction of bone leads to increased levels of calcium in the blood (hypercalcemia). A high calcium level may mean that multiple myeloma has caused substantial bone damage.
  3. Hemoglobin level. The level of hemoglobin indicates the number of red blood cells. Multiple myeloma cells crowd out healthy blood cells, so a low hemoglobin level (anemia) may indicate a high level of multiple myeloma cells in the bone marrow.
  4. Severity of bone damage. X-rays are used to find areas of bone damage. Multiple sites may indicate advanced multiple myeloma.

In the Durie-Salmon Staging System, Stage I represents the least amount of tumor cells and Stage III represents the largest amount; Stage II levels are in between Stages I and III. The stages are then subcategorized into A or B. The A classification indicates little or no kidney damage, and the B classification indicates significant kidney damage.

Table 1. Revised International Staging System (RISS) For Multiple Myeloma

Stage Description
Stage I Serum Beta-2-microglobulin, less than 3.5 mg/L and serum albumin, 3.5 g/dL or more and no high-risk cytogenetics** and normal LDH.
Stage II
Not Stage I or Stage III.
Stage III Serum Beta-2-microglobulin, 5.5 mg/L or more and high-risk cytogenetics** or high LDH.

**Cytogenetics is the field of study that analyzes the number and structure of human chromosomes. Researchers have identified certain high-risk cytogenetics that may be present in some people with multiple myeloma.

Table 2. Durie-Salmon Staging System

Stage Description
Stage I Hemoglobin levels are slightly below normal, but above 10 grams per deciliter of blood.
Calcium levels are in the normal range (12 milligrams per deciliter of blood or less).
M-protein levels are relatively low (less than 5 grams per deciliter for IgG; less than 3 grams per deciliter for IgA; less than 4 grams per 24-hour for urinary light chain).
Bone X-rays are normal or show only one area of bone damage.
Stage II Neither Stage I nor Stage III.
Stage III Hemoglobin levels are very low (less than 8.5 grams per deciliter of blood).
Calcium levels are high (more than 12 milligrams per deciliter of blood).
M-protein levels are high (more than 7 grams per deciliter for IgG; more than 5 grams per deciliter for IgA; more than 12 grams per 24-hour for urinary light chain).
Bone X-rays show at least three areas of bone damage.

These letters may be added to the Durie-Salmon stage to indicate additional factors:
A: Mostly normal kidney function. B: Abnormal kidney function.

Used with permission of the American Joint Committee on Cancer (AJCC), Chicago, Illinois. The original and primary source for this information is the AJCC Cancer Staging Manual, Eighth Edition (2017) published by Springer Science+Business Media.


The Common Signs of Multiple Myeloma


The most common signs of multiple myeloma, which are attributed to the same factors used to stage multiple myeloma, can be described with the CRAB acronym:

Calcium level – the disease may cause elevated calcium levels in the blood

Renal (kidney) function – kidney failure may result from damage to the kidneys caused by the multiple myeloma protein

Anemia – low red blood cell counts may be caused by cancer cells slowing the growth of healthy bone marrow cells

Bone lesions – multiple myeloma cells can cause bone damage (lytic lesions), thinning of the bones (osteoporosis) or a compression fracture of the spine



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