Multiple Myeloma: Stages

Aprobado por la Junta Editorial de Cancer.Net, 07/2022

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


What is cancer staging?

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 recommend the best kind of treatment, and it can help predict a patient's prognosis, which is the chance of recovery. There are different stage descriptions for different types of cancer.

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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 either:

  • Asymptomatic. This means the person does not have symptoms and signs of the disease. 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 Types of Treatment).

  • Symptomatic. This means the person has symptoms and signs of the disease. Patients with symptoms, or who are about to develop symptoms, need treatment.

The symptoms related to myeloma are described with the mnemonic acronym "CRAB," with each letter corresponding to a symptom:

  • Calcium levels are increased, which is known as hypercalcemia. This is defined as a serum calcium level greater than 0.25 mmol/L above the upper limit of normal or a level that is greater than 2.75 mmol/L.

  • Renal, or kidney, problems, identified as a creatinine level higher than 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 less than 10 g/dL.

  • Bone pain or lesions, including:

    • 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 1 or more CRAB feature need active treatment for the myeloma.

People may also be treated, even if they do not have CRAB features, if any of the following conditions apply:

  • More than 60% of the cells in the bone marrow are plasma cells.

  • The involved-to-uninvolved free light chain ratio is greater than 100, based on serum testing, with absolute values greater than 100 mg/L or 10 mg/dL. The light chain is a fragment of an antibody and is the product of cancerous plasma cells. The light chains are classified as kappa or lambda. The plasma cells of myeloma will secrete excess amounts of either of these light chains.

  • Bone lesions seen on MRI or PET-CT scans (see Diagnosis).

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Revised International Staging System

The Revised International Staging System (R-ISS) is now used more commonly to classify multiple myeloma. The R-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, lactase dehydrogenase (LDH), and serum beta-2 microglobulin (β2-M) and whether high-risk chromosomes are found using the fluorescence in situ hybridization (FISH) test (see Diagnosis).

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: All of the following apply:

  • β2-M less than 3.5 mg/L

  • Serum albumin of 3.5 g/dL or more

  • Normal LDH

  • No high-risk chromosome changes in myeloma cells found by FISH test

Stage II: Not stage I or stage III.

Stage III: β2-M is more than 5.5 mg/L, plus one of the following:

  • Myeloma cells have high-risk chromosome changes found by FISH test

  • High LDH

The R-ISS is most commonly used to predict prognosis. Higher blood levels of LDH indicate a poorer prognosis.

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.

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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 cumulative 1% chance per year of developing myeloma or, rarely, other types of blood problems such as chronic lymphocytic leukemia (CLL), lymphoma, Waldenstrom macroglobulinemia, or amyloidosis. For this reason, a person with MGUS should be regularly monitored for health changes by their 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 (10% to 60% of all cells in marrow are plasma cells). 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 treatment being studied in a clinical trial. Osteopenia is a 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 if the disease is progressing and especially for those who are at risk of developing symptoms within 18 months to 2 years.

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The R-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.

  • Higher blood levels of LDH indicate a poorer prognosis.

  • Abnormalities of chromosomes (determined by cytogenetics) in the cancer cells may show how aggressive the cancer is. This approach to testing the genetics of the myeloma include FISH and even the testing of individual gene mutations.

  • 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 your doctor about prognosis in a separate article on this website.

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Information about the cancer’s stage will help the doctor recommend a specific treatment plan. The next section in this guide is Types of Treatment. Use the menu to choose a different section to read in this guide.