Multiple myeloma is a type of blood cancer that begins in plasma cells, a kind of white blood cell found in the bone marrow. Unlike solid tumors, myeloma doesn’t form a single mass, so staging looks different compared to cancers that are solid. Instead, a specific staging system is used to look at lab results, genetic features, and the extent of bone or organ involvement to understand how advanced the disease is.

Staging in multiple myeloma matters because it helps your care team estimate how aggressive the disease might be and choose the best treatment approach for you. The most widely used system today is the Revised International Staging System (R-ISS). This combines blood tests, genetic studies, and imaging to place myeloma into three stages.

How staging is determined

Staging multiple myeloma doesn’t involve measuring the size of a tumor like in other cancers. Instead, doctors look at a few key pieces of information to understand how active the disease is. First, blood tests are done to check for proteins made by myeloma cells. Two important ones are called beta-2 microglobulin and albumin. The levels of these proteins can show how much myeloma is in the body and how it may be affecting your health. Doctors also check another marker called LDH, which can sometimes mean the disease is acting more aggressively.

In addition to bloodwork, a bone marrow sample may be taken to look for certain genetic changes that can affect how the myeloma behaves. Imaging tests such as X-rays, MRIs, or PET scans may also be used to see if the disease is causing bone damage. Together, these results give your care team a clear picture of how advanced the myeloma is and help guide your treatment plan.

Stage I (R-ISS I)

In Stage I, the beta-2 microglobulin level is low, albumin is normal, LDH is within the normal range, and there are no high-risk genetic changes. This stage generally represents less aggressive disease. Some people may not have noticeable symptoms, while others may experience issues like mild anemia, fatigue, or bone pain.

Stage II (R-ISS II)

Stage II is considered the middle ground. It applies when the test results don’t fit the criteria for Stage I or Stage III. The risk is considered moderate, and symptoms may be more apparent. Patients at this stage often notice fatigue, more frequent infections, bone discomfort, or early signs of kidney function changes.

Stage III (R-ISS III)

Stage III reflects more advanced disease. In this stage, the beta-2 microglobulin level is high, LDH is elevated, and/or high-risk genetic abnormalities are found. The disease tends to behave more aggressively. Symptoms are often more pronounced and may include severe bone pain, fractures, significant anemia, frequent infections, and worsening kidney problems.

Why staging matters

While multiple myeloma is incurable, it’s highly treatable at every stage. Knowing the stage helps determine the right intensity of therapy, your eligibility for targeted drugs or immunotherapy, and what supportive care you need to help protect bones, kidneys, and overall quality of life. 

Staging is just one piece of the puzzle, and your treatment plan will always be personalized to your specific genetic profile, overall health, and how your disease responds to therapy.

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