If you’re living with multiple myeloma, understanding how advanced your condition is can help you feel prepared for treatment. Blood cancer doctors, known as hematologists, assign a stage to multiple myeloma to predict how quickly the disease may progress. Recommendations about multiple myeloma treatment are also based partly on the stage.

Historically, two systems were used to stage multiple myeloma: the International Staging System and the Durie Salmon Staging System. Now, hematologists exclusively use the Revised International Staging System (R-ISS), which recognizes three myeloma stages. These stages are based on clinical test results rather than an individual’s myeloma symptoms.

Some doctors think of related plasma cell disorders as early stages of multiple myeloma without symptoms. These conditions include monoclonal gammopathy of undetermined significance (MGUS) and smoldering multiple myeloma. However, this article focuses on the staging of multiple myeloma at diagnosis and its progression.

Revised International Staging System

Since 2015, the R-ISS has been recognized as the most reliable tool for predicting how multiple myeloma might progress. Unlike older models, this system doesn’t consider X-rays or bone lesions (bone damage). Instead, the R-ISS uses four biological markers to classify the myeloma stage. Three markers are proteins that can be measured in blood tests, and the fourth is based on genetic changes in the cancer cells’ chromosomes.

Abnormal Protein Levels

As multiple myeloma progresses, certain protein levels in the blood can change. Doctors use levels of albumin, beta-2 microglobulin, and lactate dehydrogenase (LDH) to determine the disease stage.

Albumin

Albumin is a protein in blood plasma that helps keep fluid inside blood vessels. It also carries important nutrients, such as calcium, throughout your body. In stage 1 multiple myeloma, albumin levels are normal but may decrease as the disease progresses.

Beta-2 Microglobulin

Myeloma cells produce high levels of certain proteins, including:

• Free light chains
• M protein
• Beta-2 microglobulin

Higher amounts of beta-2 microglobulin are associated with later stages of multiple myeloma and indicate more aggressive disease.

Lactate Dehydrogenase

LDH is an enzyme that helps convert blood glucose (sugar) into energy in blood cells. Unhealthy cells, such as cancer cells, can produce extra LDH. High LDH levels may indicate damaged or cancerous cells and are more common in the later stages of multiple myeloma.

Changes in Cancer Cell Genes

Hematologists use cytogenetic studies to check for specific gene changes in the cancer cells. These tests look for abnormalities in chromosome structure that could increase the risk of cancer progression. In multiple myeloma, three specific chromosome changes are considered “high risk” because they’re linked to more aggressive disease. Other chromosomal abnormalities are considered “standard risk.”

Cytogenetic studies require a sample of bone marrow — the spongy tissue inside bones where blood cells are made. The sample is collected during a procedure called a bone marrow biopsy.

Multiple Myeloma Stage 1

Stage 1 multiple myeloma has all the following characteristics:

• No high-risk findings in cytogenetic studies
• Albumin levels above 3.5 grams per deciliter
• Beta-2 microglobulin levels below 3.5 milligrams per liter
• Normal LDH levels

Most people with multiple myeloma stage 1 live more than five years without their cancer progressing. This is called progression-free survival. In the 2015 study, 55 percent of people with stage 1 multiple myeloma were progression-free at five years. On average, their cancer took 66 months (about 5.5 years) to progress.

Learn more about stage 1 multiple myeloma.

Multiple Myeloma Stage 2

Stage 2 multiple myeloma includes features that fall between those of stages 1 and 3. Test results show disease progression that’s more advanced than stage 1 but not as severe as stage 3.

In the 2015 study, 36 percent of people with stage 2 multiple myeloma reached progression-free survival at five years. On average, their cancer progressed after 42 months (about 3.5 years).

Learn more about stage 2 multiple myeloma.

Multiple Myeloma Stage 3

Stage 3 multiple myeloma is defined by beta-2 microglobulin levels of 5.5 milligrams per liter or higher and at least one of these two features:

• High-risk cytogenetic findings
• Elevated LDH levels

In the 2015 study, 24 percent of people with stage 3 multiple myeloma achieved progression-free survival at five years. On average, their cancer progressed after 29 months (about 2.4 years).

Learn more about stage 3 multiple myeloma.

Relapsed and Refractory Myeloma

Although not part of the official R-ISS, other factors can influence treatment options. If your multiple myeloma returns after successful treatment, it’s called a relapse. Cancer that does not respond to treatment is referred to as refractory multiple myeloma.

Your oncologist may restage the cancer based using the R-ISS criteria, but they’ll likely take a different treatment approach. Progression isn’t usually as favorable for relapsed or refractory multiple myeloma.

Learn more about refractory or relapsed multiple myeloma.

Refractory Multiple Myeloma

Refractory multiple myeloma is not included in the three R-ISS stages. This advanced form of blood cancer no longer responds to treatment and usually leads to death. Refractory multiple myeloma symptoms may include more severe versions of those seen throughout multiple myeloma. These symptoms may include:

• Hypercalcemia (high calcium levels)
• Worsening kidney function
• Anemia (low levels of red blood cells)

People may also experience bone pain, fractures, and fatigue. These symptoms are also common in less advanced multiple myeloma but tend to get worse as the disease progresses.

Understanding Your Unique Circumstance

Staging helps doctors recommend appropriate treatment options, which may include participation in clinical trials. Knowing your stage can also help you see where you fit within the current research. However, your individual health traits also influence your disease progression and prognosis (outlook).

Certain factors may improve your chances of living longer without cancer progression. These factors include:

• Healthy kidney function
• Few or well-managed additional health issues
• Younger age

If you have any questions about your specific situation, don’t hesitate to reach out to your oncology team for guidance.

Talk With Others Who Understand

MyMyelomaTeam is the social network for people with myeloma. On MyMyelomaTeam, more than 27,000 members come together to ask questions, give advice, and share their stories with others who understand life with myeloma.

Did your oncologist discuss your myeloma stage with you when you were diagnosed? Share in the comments below, or start a conversation by posting on your Activities page.