Multiple Myeloma


Doctors use a process called staging to describe the extent of multiple myeloma and predict treatment outcomes. Results of your diagnostic tests and pathology report will be used for staging, and additional tests may be ordered. Staging provides essential information that helps guide your treatment options.

The two staging systems used 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). Each system has Stages I to III, but they do not mean the same thing.

How the RISS Works

The RISS uses four factors to distinguish between Stages I, II and III: the level of three predictive proteins – albumin, beta-2-microglobulin and lactate dehydrogenase (LDH) – measured in the blood, and chromosomal (genetic) abnormalities that may be detected in the myeloma cells.

  • 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 is made by malignant myeloma cells. The level increases as myeloma progresses, so high levels may mean that the cancer is more advanced.
  • Lactate dehydrogenase (LDH) helps cells convert sugar to energy. High levels of LDH may indicate a more advanced myeloma.
  • Genetic abnormalities are assessed through fluorescent in situ hybridization (FISH), a laboratory test that is done on sample myeloma cells from the bone marrow biopsy. 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. Genetic changes can include specific chromosomes that are broken, rearranged or missing.

The field of study that evaluates chromosomes for changes and abnormalities is called cytogenetics. Cytogenetic analysis may help your doctor determine the treatment plan most likely to be effective for you.

Durie-Salmon Staging System Explained

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

  1. M-protein. Large amounts of this abnormal protein in the blood or urine may indicate 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.

Staging can be complex and may seem confusing, so it’s important to ask your doctor or nurse to explain anything that is unclear to you. Learn all you can about your diagnosis, including your type and stage of multiple myeloma, test results and any genetic findings. This knowledge will help you make informed decisions and be a more active partner in planning your treatment and managing your overall care.

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 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.

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