Multiple Myeloma

Staging

Doctors rely on many tests to diagnose and stage multiple myeloma, including a thorough physical exam, imaging studies, blood and urine tests, bone marrow biopsy and molecular testing. Staging provides your doctor with essential information to understand the extent of the myeloma, determine the best treatment options for you and predict the prognosis (outcome).

Staging multiple myeloma can be complex and may seem confusing. Learn all you can about your diagnosis, including your type and stage of multiple myeloma and what your test results and any genetic findings mean. Pay particular attention to molecular testing, which is performed on the tumor or a bone marrow sample to look for specific chromosomes, genes, proteins and other factors that help your doctor understand how the disease may behave.

Ask your doctor or nurse to explain anything that is unclear to you.


Commonly Used Staging Systems

The staging systems for multiple myeloma are the Revised International Staging System (RISS), which is commonly used (see Table 1), and the Durie-Salmon Staging System (see Table 2). Both have three stages, though they do not mean the same thing.

Some of the molecular tests that may be performed for staging include the following:

  • Cytogenetics evaluates cells for chromosome abnormalities by looking for genetic changes at the DNA level. Abnormalities, such as chromosomes that are broken, rearranged or missing, may indicate the level of disease. Cytogenetic analysis may help your doctor determine the treatment plan most likely to be effective for you.
  • Fluorescence in situ hybridization (FISH) detects abnormal cells that may be associated with a more advanced myeloma. During the test, fluorescent dye is used to highlight genes or areas of chromosomes under a microscope to look for abnormalities that may be associated with more advanced or aggressive myeloma.  
  • Measurable/minimum residual disease (MRD) testing is used to determine the number of cancer cells that are usually present in bone marrow. “MRD positive” means disease is still detected. “MRD negative” means no disease is detected.

Revised International Staging System (RISS)

The RISS uses the following factors to assign one of three stages:

  • Albumin level. Albumin is made in the liver, and the blood albumin level can help your doctor determine how well your liver and kidneys function. Low levels may signal a more advanced myeloma.
  • Beta-2-microglobulin level. This is made by malignant myeloma cells. The level in the blood increases as myeloma progresses, so high levels may mean that the cancer is more advanced. 
  • Lactate dehydrogenase (LDH) level. LDH helps cells convert sugar to energy. High levels of LDH in the blood may indicate a more advanced myeloma.
  • Genetic abnormalities. Biomarker testing of the tumor is performed to look for abnormalities and changes in chromosomes, genes, proteins and other factors unique to the tumor. The types of testing used include cytogenetics, fluorescence in situ hybridization (FISH) and measurable/minimum residual disease (MRD) testing.  

Durie-Salmon Staging System

The Durie-Salmon Staging System uses blood, urine and imaging test results to measure the amount of abnormal plasma cells present and to determine tumor size and/or extent of cancer in the body. Four main factors are considered:

  1. M-protein. Large amounts of this abnormal protein in the blood or urine may indicate that a high number of malignant plasma cells are present.
  2. Calcium. A high calcium level in the blood (hypercalcemia) may mean that multiple myeloma has caused substantial bone damage.
  3. Hemoglobin. This essential protein is found in red blood cells, and the level indicates the number of red blood cells. Healthy blood cells are crowded out by multiple myeloma cells in the bone marrow, so a low hemoglobin level (anemia) may mean a high level of multiple myeloma cells.
  4. Bone damage. Imaging tests are used to identify the location and severity of bone damage in the body. Multiple sites may indicate advanced multiple myeloma.

Stage I indicates the smallest amount of tumor cells present, and Stage III represents the largest amount. Once the stage is determined, it is subcategorized to signify the level of kidney damage: “A” indicates little or no change in function, and “B” indicates significant kidney damage.

Sometimes your doctor will reassess your stage after treatment or if cancer recurs. This is known as restaging. If it is necessary, it typically involves the same diagnostic tests used for the original staging.

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 nor 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.

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.

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.