Multiple Myeloma: Stages

Approved by the Cancer.Net Editorial Board, 10/2016

ON THIS PAGE: You will learn about how doctors describe myeloma’s growth or spread. This is called the stage. To see other pages, use the menu.

Staging is a way of describing where a cancer is located, if or where it has spread, and whether it is affecting other parts of the body.

Doctors use diagnostic tests to find out the cancer's stage, so staging may not be complete until all of the tests are finished. Knowing the stage helps the doctor decide what kind of treatment is best and can help predict a patient's prognosis, which is the chance of recovery. There are different stage descriptions for different types of cancer.

For myeloma, it is important to begin with whether the patient is experiencing symptoms. It is common to classify people with newly diagnosed myeloma as being either symptomatic from the disease (having symptoms and signs) or asymptomatic (not having any symptoms). Patients without symptoms are generally watched closely without specific treatment, although therapies are sometimes offered to stop the disease from growing or spreading. This is called active surveillance for smoldering myeloma (see Treatment Options). Patients with symptoms or who are about to develop symptoms need treatment.

The symptoms related to myeloma are described with the mnemonic CRAB. They include hypercalcemia (high blood Calcium), poor Renal or kidney function, Anemia, and Bone pain or bone lesions.

  • Calcium levels are increased. This is defined as a serum calcium level >0.25 mmol/L above the upper limit of normal or a level that is >2.75 mmol/L.

  • Renal problems, identified as a creatinine >173 mmol/L.

  • Anemia is defined as having a low hemoglobin level, which is 2 g/dL below the lower limit of normal or a hemoglobin level that is <10 g/dL.

  • Bone lesions include:

    • lytic lesions (areas of bone damage)

    • osteoporosis (thinning of the bones)

    • compression fracture of the spine

Other symptoms include symptomatic hyperviscosity (thickening of the blood), amyloidosis, and repeated serious bacterial infections (more than 2 episodes in 12 months). Patients with CRAB features require active treatment.

Patients may also be treated, even if they don’t have CRAB features, if any of the following conditions apply:

  • >60% bone marrow plasma cells

  • Kappa-to-lambda ratio >100, based on serum testing, with absolute values >100 mg/L or 10 mg/dL

  • Bone lesions seen on MRI or PET-CT imaging

Durie-Salmon System

The Durie-Salmon system has traditionally been used for the staging of myeloma. This staging system is good for assessing the extent of the disease and/or size of the tumor. According to this system, there are 3 stages, called stages I, II, or III (1, 2, or 3). Each stage is further classified into A or B, depending on whether kidney function has been affected. The B classification means that there is significant kidney damage.

Stage I: Many patients with stage I myeloma show no symptoms because there are fewer cancer cells in the body. If the cancer has affected kidney function, the prognosis may be worse regardless of the stage. Factors characteristic of stage I include:

  • Number of red blood cells is within or slightly below normal range

  • Normal amount of calcium in the blood

  • Low levels of M protein in the blood or urine

    • M protein <5 g/dL for IgG; <3 g/dL for IgA; <4 g/24 h for urinary light chain

    • No bone damage on x-rays or only 1 bone lesion is visible

Stage II: More cancer cells are present in the body in stage II. Again, if kidney function is affected, then the prognosis worsens regardless of the stage. Criteria for stage II are defined as those that fit neither stage I nor stage III.

Stage III: Many cancer cells are present in the body at stage III. Factors characteristic of this stage include:

  • Anemia, with a hemoglobin <8.5 g/dL

  • Hypercalcemia

  • Advanced bone damage (3 or more bone lesions)

  • High levels of M protein in the blood or urine

    • M protein >7 g/dL for IgG; >5 g/dL for IgA; >12 g/24 h for urinary light chain

International Staging System

The International Staging System (ISS) is now used more commonly to classify multiple myeloma. It defines the factors that influence patient survival. The ISS is based on data collected from people with multiple myeloma from around the world. The system has 3 stages based on the measurement of serum albumin and the levels of serum β2-M.

Recent efforts have been made to further classify myeloma based on patterns of gene expression in myeloma cells. This is an ongoing area of research.

Stage I: β2-M <3.5 mg/L with a serum albumin of 3.5 g/dL or more

Stage II: Either of these 2 criteria:

  • β2-M between 3.5 mg/L and 5.5 mg/dL

  • Albumin <3.5 g/dL

Stage III: β2-M >5.5 mg/L

This system has recently been revised to include serum lactase dehydrogenase (LDH) and high-risk gene abnormalities defined by FISH. It is most commonly used to predict prognosis. Higher blood levels of LDH indicate a poorer prognosis. Abnormalities of chromosomes (as defined by the results of cytogenetic testing) in the cancer cells may also show how aggressive the cancer is and influence how the disease progresses.

Recurrent or relapsed myeloma. Myeloma that returns after a period of being in control after treatment is called recurrent myeloma or relapsed myeloma. If there is a recurrence, the cancer may need to be staged again (called re-staging) using one of the systems above.

Other classifications

Some people have no symptoms of myeloma, but they may have abnormal plasma cells producing M protein. Doctors generally monitor these people closely, and active treatment does not begin unless the person starts to experience symptoms and/or shows signs of damage to major organs, called end organ damage; this is so-called symptomatic myeloma.

Monoclonal gammopathy of undetermined significance (MGUS)

This condition occurs when people have a low level of M protein, meaning there are small amounts of abnormal plasma cells, but they do not have any other evidence of myeloma, such as bone damage, excessive plasma cells in the marrow, or low numbers of components of the blood count, such as red blood cells, white blood cells, and/or platelets. People with MGUS have a 1% chance per year of developing myeloma or, rarely, other types of blood problems such as chronic lymphocytic leukemia (CLL), lymphoma, Waldenstrom's macroglobulinemia, or amyloidosis. For this reason, a person with MGUS should be regularly monitored for health changes by his or her doctor.

Smoldering multiple myeloma (SMM) or asymptomatic myeloma

People who are diagnosed with SMM have higher levels of M protein and more plasma cells in the bone marrow than people with MGUS. However, there is still no evidence of symptoms or signs of myeloma, such as significant bone disease or anemia. A person with SMM may be prescribed bisphosphonates for symptoms of osteoporosis or osteopenia and/or a new therapy being studied in a clinical trial. Osteopenia is condition in which a person has a low density of bone minerals. Most people with SMM eventually develop myeloma. For this reason, the health of people with SMM should be closely monitored by their doctors, who may recommend starting treatment when there is progression of disease and especially to patients who are at the risk of developing symptoms within 18 months to 2 years.

Prognosis

The ISS of myeloma gives information about prognosis and predicts the person’s chance of recovery. Researchers are also looking at other ways to predict prognosis for people with multiple myeloma. Some of the current approaches for evaluating prognosis include:

  • High levels of β2-M may indicate that a large number of myeloma cells is present and that kidney damage has occurred. The level of this protein increases as myeloma becomes more advanced.

  • Lower amounts of serum albumin may indicate a poorer prognosis.

  • Lactase dehydrogenase (LDH) is an enzyme. Higher blood levels of LDH indicate a poorer prognosis.

  • Abnormalities of chromosomes (cytogenetics) in the cancer cells may show how aggressive the cancer is. This approach to testing the genetics of the myeloma includes FISH.

  • A plasma cell labeling index can be done in a specialized laboratory using bone marrow samples to find out how fast the cancer cells are growing.

Learn more about talking with the doctor about prognosis.

Information about the cancer’s stage will help the doctor recommend a specific treatment plan. The next section in this guide is Treatment Options. Or, use the menu to choose another section to continue reading this guide.