Multiple Myeloma


Staging provides essential information, describing the extent of the multiple myeloma, helping guide the treatment plan and predicting treatment outcomes (prognosis). Test results during the sometimes complex diagnostic process, including a thorough physical exam, imaging studies, blood and urine tests, bone marrow biopsy and molecular testing, are considered. Once the tests confirm the diagnosis, your doctor will assign a stage.

Researchers have discovered that certain chromosome and molecular abnormalities may be found in this cancer type. Molecular testing will be performed on the tumor or a bone marrow sample to look specifically for changes in chromosomes, genes, proteins and other factors that may indicate the aggressiveness of the disease. This information further affects the treatments that may be available to you.

You will likely hear many terms you have not heard before, which can make understanding your diagnosis challenging. Ask your doctor to fully explain those terms, along with your type and stage and what your test results and any genetic findings mean. You will feel more confident making treatment decisions when you feel fully informed.

Determining Prognosis

The information gathered for the staging process also helps doctors understand the prognosis (chance of recovery). Certain factors affect prognosis and treatment options. They include the following:

  • The type of plasma cell neoplasm
  • The stage of the disease
  • Whether a certain immunoglobulin (antibody) is present
  • Whether there are certain genetic/genomic changes
  • Whether the kidneys are damaged
  • Whether the cancer responds to initial treatment or recurs (comes back)

Understanding the Staging Systems 

Your doctor may refer to the staging systems that are used for multiple myeloma: the Revised International Staging System (RISS), which is commonly used (see Table 1), and the Durie-Salmon Staging System (see Table 2). Both systems have three stages, but they have different meanings. A new version of the RISS has been proposed. Ask your physician about the staging system being used for your diagnosis.

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 considers four main factors:

  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.

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.