Understanding Multiple Myeloma Stages and Prognosis

Medically Reviewed by Zilpah Sheikh, MD on August 08, 2024
12 min read

Multiple myeloma is a cancer of your bone marrow. Specifically, it affects your plasma cells, which are white blood cells that make antibodies to fight germs and prevent infection and disease.

When you're first diagnosed with multiple myeloma, your doctor will assign it a stage that describes how serious it is at that point. The stage is usually indicated with a number, and that number has a lot to do with the type of treatment your doctor will recommend and what you can expect from your disease going forward.

There's no cure for multiple myeloma, but treatment can bring it into remission, meaning you don't have any sign of the disease.

The same tests your doctor uses to know if you have multiple myeloma will also help them tell what stage it's in. These include:

  • Blood tests
  • Urine (pee) tests
  • Bone marrow biopsy
  • X-rays and other imaging tests
  • Genetic tests of the cancer cells

Staging is the process by which your doctors will figure out if your cancer has spread to your other organs and, if so, how far it has spread. The stage describes how serious your cancer is and gives your doctors a place to start when deciding how best to treat it.

Cancer staging can be a complicated process. Different staging systems may use different factors in determining how serious your cancer is. Doctors use a couple of different staging systems for multiple myeloma. The two main systems for multiple myeloma are the Revised International Staging System (R-ISS) and the Durie-Salmon staging system.

Doctors usually use the R-ISS for staging multiple myeloma these days. This is because it's a bit simpler than the Durie-Salmon staging system, and it seems to give a better idea of prognosis for most people. Doctors started using the ISS in 2005. It was revised in 2015 by changing some of the biomarkers that're used. Biomarkers are levels of chemicals in your body that give a snapshot of what is happening in your body at that time.

The R-ISS is based on the measurements of four biomarkers, including:

The amount of albumin in your blood. Albumin is a protein your body makes that circulates in your blood. It gives your doctor an idea of how well your liver and kidneys are working.

The amount of beta-2 microglobulin (B2M) in your blood. This is a protein that your body normally makes in small amounts. But cancer can cause you to make lots more of it. High levels of this protein in your blood can be caused by certain blood and bone marrow cancers, such as multiple myeloma, chronic lymphocytic leukemia, and some lymphomas.

The amount of lactate dehydrogenase (LDH) in your blood. This protein helps your cells make energy, and it's found in all your tissues. But it's highest in your muscles, liver, kidneys, and red blood cells. When you have disease or tissue damage, your cells release LDH into your bloodstream, so high levels can show you have something damaging your muscles and organs.

The gene abnormalities in your bone marrow cells. Your doctor will take a biopsy from your bone marrow and send it for a genetic test called cytogenetics using a technique called fluorescence in situ hybridization. The lab technician will look at the chromosomes from your bone marrow cells under a microscope. These cells may have too many chromosomes, too few chromosomes, or abnormal chromosomes where some of the information has been deleted or moved. Doctors divide these abnormalities into categories based on how serious they are.

Based on your levels on these four biomarkers, your doctors will assign a stage, as follows:

Stage I

  • Albumin level: Greater than or equal to 3.5 grams per deciliter
  • B2M level: Less than or equal to 3.5 milligrams per liter
  • LDH level: Normal, which is generally about 135-225 units per liter
  • Standard-risk cytogenetics

Stage II

Your biomarker levels don't fit in either stage I or III.

Stage III

  • Albumin level: Less than or equal to 3.5 grams per deciliter
  • B2M level: Greater than or equal to 5.5 milligrams per liter
  • LDH level: Greater than normal
  • High-risk cytogenetics, including a deletion in chromosome 17 and rearrangements between chromosomes 4, 14, and 6. You may see this listed as del(17p), t(4:14), or t(14:6) in a pathology report.

The Durie-Salmon staging system is an older system that doctors don't use as often because it's more complex. It's based on the total number of cancer cells in your body and some biomarkers, including:

The amount of hemoglobin in your blood. Hemoglobin is a protein in your red blood cells. It carries oxygen from your lungs to your other tissues. Blood disorders and certain diseases can cause your hemoglobin levels to be higher or lower than normal.

The amount of calcium in your blood and bone imaging to see if you have lesions. Lesions on your bones can make you leach calcium into your bloodstream, so your blood calcium may be higher than normal.

The amount of monoclonal (M) protein in your blood and pee. Abnormal plasma cells make a protein called M protein or M spike. These proteins are antibodies that have a couple of different components: IgG and IgA. Myeloma cells are one of the types of cells that make this M protein. If your plasma cells are making M protein, your doctor will be able to detect it in your blood and pee.

How well your kidneys are working according to the amount of a protein called serum free light chains in your pee.

Based on your levels of myeloma cells and on these biomarkers, your doctors will assign a stage as follows:

Stage I

  • Myeloma cell mass: Greater than or equal to 600 billion per square meter
  • Hemoglobin level: Greater than 10 grams per deciliter
  • Calcium level: Greater than 8.5 milligrams per deciliter but less than 12 milligrams per deciliter
  • Bone imaging: Normal bone structure or only one bone plasmocytoma (a plasma cell tumor)
  • M protein: IgG component less than 5 grams per deciliter and IgA component less than 3 grams per deciliter
  • Urine light chains: Less than 4 grams per 24 hours

Stage II

  • Myeloma cell mass: Between 600 and 1,200 billion per square meter
  • Your biomarker levels don't fit in either stage I or III
  • You may also get a substage based on your creatinine level. Creatinine levels tell your doctor how well your kidneys are working. Stage IIA would be for a creatinine level less than or equal to 2 milligrams per deciliter. Stage IIB would be if your creatinine levels are greater than 2 milligrams per deciliter. This would indicate you have some amount of kidney damage.

Stage III

  • Myeloma cell mass: Greater than 1,200 billion per square meter.
  • Hemoglobin level: Less than 8.5 grams per deciliter.
  • Calcium level: Greater than 12 milligrams per deciliter.
  • Bone imaging: More than 3 bone lesions.
  • M-protein: IgG component greater than 7 grams per deciliter and IgA component greater than 5 grams per deciliter.
  • Urine light chains: Greater than 12 grams per 24 hours.

 CRAB criteria are a way for your doctor to tell if you have organ damage because of your cancer. These criteria include:

  • Calcium levels that are high (hypercalcemia), with a blood calcium level greater than 11 milligrams per deciliter
  • Renal insufficiency, with a creatinine clearance less than 40 milliliter per minute or greater than 2 milligrams per deciliter
  • Anemia, with a total hemoglobin value less than 100 grams per liter
  • Bone lesions, with one or more seen on X-ray, CT, or PET/CT scan

This is a precursor to multiple myeloma that may or may not develop into active multiple myeloma. When you have it, you probably won't have any symptoms, but you will have the genetic changes that cause multiple myeloma.

If you have smoldering multiple myeloma, you will show the following on lab tests:

  • M protein level of greater than 3 grams per deciliter in your blood. Or 500 milligrams or more of M protein on a 24-hour pee test.
  • At least 10%-59% of your bone marrow is plasma cells on a bone marrow biopsy, but you don't have any sign of bone lesions or kidney damage.
  • Normal levels of calcium and normal cell counts on a blood test.

Many people with smoldering multiple myeloma only find out they have it when M proteins show up in their blood or pee during a routine checkup. So you can have this for many years before it develops into active multiple myeloma. And sometimes, it never develops into multiple myeloma. Right now, there's no test to know which people with smoldering multiple myeloma will progress to active multiple myeloma.

But your risk of progression seems to be highest during the first 5 years after you're diagnosed. After the first 5 years, your risk of progression goes down. Your doctor will test you periodically for any signs of this and will be prepared to start treatment right away.

If you're having symptoms or you have signs that the cancer has damaged your organs, then you have active myeloma. The criteria for active myeloma include:

  • A bone marrow biopsy that shows plasma tumor cells make up at least 10% of your bone marrow.
  • You have at least one myeloma-defining event (MDE).

MDEs include any of the following:

  • There is presence of CRAB criteria.
  • Monoclonal plasma cells are greater than or equal to 60% of your bone marrow on biopsy.
  • There are one or more bone lesions on MRI.
  • Ratio of involved-to-uninvolved serum free light chain is greater than or equal to 100. The involved serum free light chain must be greater than or equal to 100 milligrams per liter, and M protein in your pee must be at least 200 milligrams per 24 hours.

As active multiple myeloma gets worse, you'll likely feel sicker, with fatigue or bone pain. You may have anemia, bleeding problems, or a lot of infections. Other symptoms of advanced multiple myeloma include unusual fractures, shortness of breath, weakness, feeling very thirsty, and belly pain.

Refractory myeloma is when your disease doesn't respond to treatment or comes back after treatment. There are two types:

Relapsed and refractory myeloma. This is a relapse of disease when you've had some response to treatment, then either get nonresponsive while on salvage therapy (treatment given when standard treatment doesn't work) or progress within 60 days of your last treatment.

Primary refractory myeloma. You don't respond to any treatment. There are two subcategories:

  • You don't respond to treatment, but your disease doesn't progress.
  • You have primary refractory disease that is progressing.

Relapsed myeloma. After a while without treatment, you need salvage therapy but do not meet criteria for "primary refractory" or "relapsed and refractory" categories.

Remember, no two people are entirely alike. Your treatment will be tailored to you, and your response to treatment will be unique to you. And many factors can affect your outcome. Doctors use survival rates from clinical trials to estimate your outcome. But again, these are estimates based on averages from studies with many people. So these numbers can't tell your doctor how you will do as an individual. Instead, they are meant to help doctors decide how aggressively to treat your cancer. Also, treatment strategies continue to improve over time, and rapid advances have been made in the past few years in particular. So sometimes, these survival numbers don't show how well the newer treatments work.

Having said that, the main factors that doctors consider when estimating your prognosis for multiple myeloma are:

  • The stage of your cancer when you're diagnosed
  • The genetic changes that are present in the cancer cells

Doctors will talk about prognosis in terms of overall survival (OS) rate and progression-free survival (PFS) rate. OS rate is the average percentage of people who are still alive for a certain length of time after they were diagnosed or started treatment, generally 5 years. PFS rate is the average percentage of people who go through treatment without their cancer getting worse or spreading.

Based on the R-ISS:

  • For stage I, the 5-year OS is 82% and PFS is 55%
  • For stage II, the 5-year OS is 62% and PFS is 36%
  • For stage III, the 5-year OS is 40% and PFS is 24%

What these numbers show is that most people who are diagnosed with multiple myeloma in stage I or II are still living 5 years after they were diagnosed. And for people in stage I, slightly more than half go through treatment without their cancer getting worse. Fewer people who are diagnosed in stages II and III go through treatment without their cancer getting worse. However, many people who are diagnosed even in stage III are still living 5 years after their diagnosis.

High-risk cytogenetics can negatively affect your prognosis. These high-risk genetic changes include del(17p), t(4:14), and t(14:16). In general, people with these changes live for a shorter time than 5 years after diagnosis. For instance, people with t(14:16) cytogenetics have an OS of about 4.1 years and a PFS of 2.1 years. So if you have these changes, your doctor will likely take a very aggressive approach when treating your cancer.

Your doctor may suggest you enroll in a clinical trial if you are eligible. In a clinical trial, you will get leading-edge treatment for your cancer. And you will be helping future people who are diagnosed with multiple myeloma by improving their treatment options.

The stage of your multiple myeloma is just one thing that predicts how much treatment will help you. Other things that make a difference include:

Your age. The younger you are, the more likely it is that your treatment will work without your cancer getting worse.

Your results on some blood tests. These include levels of B2M, albumin, LDH, and creatinine. These results tell your doctor how much cancer you have and how well your kidneys and liver are working.

The genetic changes in your cancer.

How fast your cancer is growing. Your doctor can use a test called plasma cell labeling index to figure this out.

Your general health. Your doctor will use the performance status (PS) scale to describe your general health. They'll rate your general health on a scale of 0-4, with 0 being perfectly healthy and able to care for yourself without restrictions. A PS of 4 would indicate that you need help caring for yourself and are completely confined to your bed or wheelchair.

How you respond to treatment. For instance, some people respond really well to treatment and their cancer goes into complete or partial remission, which means you have no or very few signs or symptoms of disease.

Researchers are constantly doing clinical trials on treatments for multiple myeloma, so the treatments have gotten better in recent years. There are really good reasons to be hopeful about your outlook.

Multiple myeloma is cancer of the plasma cells in your bone marrow. To help decide on your best treatment plan, your doctor will assign your cancer a stage. They usually use the R-ISS to do this, but they may also use the Durie-Salmon staging system. Because every individual person is different, a helpful way to think about staging is as a way for your doctor to decide where to start your cancer treatment. Of course, people who are diagnosed in stage I or II do the best with treatment because they tend to be healthier at diagnosis. However, treatments for multiple myeloma continue to improve, so there are good reasons to stay optimistic about your treatment no matter what stage you were diagnosed in.

What is the life expectancy with multiple myeloma?

This depends on many factors, including the stage of your cancer at diagnosis and the kind of genetic changes your cancer has. Cancer doctors generally don't like to talk in terms of life expectancy because so many factors can affect your outcome, including how well you do during your treatment. Keeping a hopeful outlook can help. Thanks in part to newer treatments, most people diagnosed with stage I or II multiple myeloma are still living 5 years after they are diagnosed. And about 40% of people who are diagnosed in stage III are still living 5 years after they are diagnosed. These numbers will likely continue to improve as research advances the treatment options. So some people live for 10 or more years with it.

Is multiple myeloma curable?

No, unfortunately, multiple myeloma cannot be cured. This is because there's no way to completely get rid of the genetic changes in your bone marrow once you have them. Your doctor will instead focus your treatment on keeping the cancer from getting worse and reducing your symptoms so you maintain a good quality of life. However, some people do go into either complete or partial remission during treatment. This means that your have no or very few signs or symptoms of disease. The cancer could come back, but your doctor will monitor you for those signs so they can start treatment again right away.

How serious is multiple myeloma?

Multiple myeloma is a serious type of cancer that affects your blood cells and may need an aggressive treatment regimen. But it can be managed well, especially if you get diagnosed early. The best thing to do is take good care of your general health and follow your cancer care team's plan.