Multiple myeloma is a complex blood cancer that’s difficult to treat and usually not curable. When it becomes relapsed or relapsed, it can be even harder to manage. These two terms describe different ways the disease can progress after treatment — and understanding them can help people make informed decisions about what to expect next.

In this article, we explain what “relapsed” and “refractory” multiple myeloma mean, how they’re similar and different, and what treatment options may be available.

Thanks! You've successfully submitted your vote.

Sign up to view the results!

Continue with Facebook

Continue with Google

Continue with your email

By joining, you accept our Terms of Use, and acknowledge our collection, sharing, and use of your data in accordance with our Health Data and Privacy policies.

Already a Member? Log in

What Are Relapsed and Refractory Myelomas?

After being diagnosed with myeloma, most people begin first-line (or frontline) therapy — the initial treatment used to manage the cancer. These medications aim to kill myeloma cells, reduce symptoms, and help extend life. First-line therapy often includes a combination of medications, such as:

• Chemotherapy
• Targeted therapy
• Immunomodulatory drugs
• Immunotherapy
• Corticosteroids such as dexamethasone

Most people respond well to their first treatment and may go into remission, a period when symptoms improve or disappear. Remission can last for months or even years.

Relapsed multiple myeloma comes back after treatment that initially improves it. Maintenance therapy can help prolong remission.

One MyMyelomaTeam member shared words of encouragement: “I’ve been in remission for five years and feel fine. I just have a doctor phone call every 13 weeks. Good luck to everyone.”

Relapsed Multiple Myeloma

Relapsed multiple myeloma occurs when the cancer returns after treatment that that had previously helped control it. Symptoms often get worse after a period of remission. While maintenance therapy can help prolong remission, it usually doesn’t last forever. Most people living with myeloma experience one or more relapses. Over time, myeloma becomes more advanced and difficult to treat.

Refractory Multiple Myeloma

Refractory multiple myeloma occurs when the disease continues to grow or worsen despite treatment. In this case, the current therapy isn’t working well enough to control the cancer. Refractory myeloma usually means it’s time to consider a different treatment approach.

Read more about what to expect with refractory multiple myeloma.

Relapsed/Refractory Multiple Myeloma

Some people may have myeloma that is relapsed, refractory, or both. Myeloma may respond to initial treatment but become resistant over time, especially after a relapse. This is called relapsed/refractory multiple myeloma (RRMM).

You’re considered to have RRMM if you improve during first-line therapy and any of the following apply:

• Your myeloma stops responding or starts to worsen while you’re still on treatment.
• You stop seeing improvements within 60 days of your last treatment.
• You don’t achieve at least a minimal response with a given therapy.

RRMM is typically harder to treat. People may experience less symptom relief once their condition reaches this stage. They may also have a worse prognosis (outlook). However, researchers continue to develop therapies that may work better to treat RRMM.

How Common Are Relapsed and Refractory Myelomas?

Nearly all people with multiple myeloma will experience either relapsed myeloma, refractory myeloma, or RRMM. Just because your myeloma is relapsed, refractory, or even in remission now doesn’t mean it’ll stay that way. You can expect to have several cycles of remission and relapse as you undergo lines of blood cancer treatment.

Just because your myeloma is currently relapsed, refractory, or even in remission now doesn’t mean it’ll stay that way. You can expect to have several cycles of remission and relapse as you undergo lines of treatment.

Coming to terms with myeloma changes may make it easier to accept new developments in your disease. One MyMyelomaTeam member said, “I was advised that at some point I will likely relapse since multiple myeloma acts like a light switch and turns on with no obvious reason. However, I’m comforted by others I know who have relapsed and returned to remission.”

Why Myeloma Becomes Refractory

Refractory myeloma occurs when cancer cells develop genetic changes. The longer cancer cells live, grow, and divide, the more they mutate (change genetically).

Some mutations can help protect the cancer cells from being killed by medications. For example, certain mutations may allow cancer cells to pump cancer drugs back out of the cell, preventing the medication from doing its job.

Additionally, myeloma cells alter the bone marrow (spongy tissue where new blood cells are made). These changes create an environment that helps them survive. By changing their surroundings, these cells can “hide” from cancer drugs and the immune system. As a result, myeloma becomes more difficult to treat.

Relapsed and Refractory Myelomas Share Some Risk Factors

You’re more likely to experience relapsed or refractory myeloma if:

• Your remission periods are short.
• Your myeloma advances quickly.
• You’ve had an aggressive relapse in the past.
• You have specific genetic mutations.
• Your immune system is impaired.
• You have another type of cancer, such as plasma cell leukemia.

Relapsed and Refractory Myelomas Share Signs and Symptoms

There are several signs that myeloma might be getting worse. These signs are usually detected through blood tests. If tests show that myeloma signs persist during treatment, you may have refractory disease.

A doctor may diagnose a multiple myeloma relapse if a person meets certain conditions, such as:

• Increased plasma cells in the bone marrow
• Higher levels of monoclonal antibodies or other abnormal proteins made by cancerous plasma cells
• Newly formed or growing plasmacytomas (small tumors made up of plasma cells) or bone lesions
• Low levels of hemoglobin (a protein found in red blood cell that carries oxygen), which may signify anemia (low levels of red blood cells)
• High levels of kidney waste products that signify kidney failure

• High blood calcium levels

Long-term treatment or use of multiple drugs can also lead to complications. It’s important to work with your oncologist and the rest of your healthcare team as your myeloma changes over time. While you’re being treated for myeloma, your doctor will likely order regular follow-up testing. These tests look for signs of a relapse or refractory myeloma. You may need to undergo blood, urine, or imaging tests.

Even before testing, you might notice some signs of relapse. Symptoms of multiple myeloma relapse can vary. Be sure to tell your oncology team if you notice new or worsening symptoms or if you don’t feel that a treatment is helping.

New Treatments Offer Hope for Relapsed and Refractory Myelomas

Learning that you have relapsed or refractory myeloma can feel overwhelming. However, advances in therapy are improving outcomes. Over the past few decades, new treatment options have more than doubled myeloma survival rates. In the 1990s, people with myeloma lived an average of three to four years. Today, newly diagnosed people are expected to live more than eight years. This is thanks to next-generation treatments that work much better than older options.

New and more effective treatments and drug combinations can help people with relapsed or refractory myeloma live longer and enjoy an improved quality of life.

How Relapse Can Guide Treatment

If you relapse more than six months after trying a treatment, your doctor may recommend using that same therapy again. On the other hand, if you experience an early relapse within six months, you may need to try a different approach.

Typical Treatment Options

Myeloma is typically an incurable disease. Treatment of relapsed/refractory myeloma can be particularly challenging. New and more effective treatments and drug combinations can help people live longer with multiple myeloma, whether they’re dealing with relapsed versus refractory versus relapsed/refractory disease.

In recent years, the U.S. Food and Drug Administration (FDA) has approved multiple treatments, including the following:

• Daratumumab hyaluronidase-fihj (Darzalex Faspro) and isatuximab-irfc (Sarclisa) are monoclonal antibodies that recognize CD38, a protein on the surface of myeloma cells. These drugs help the immune system find and destroy those cells.
• Idecabtagene vicleucel (Abecma) is a chimeric antigen receptor (CAR) T-cell therapy. It modifies a person’s own T cells (a type of white blood cell) to help them better recognize and kill myeloma cells.
• Teclistamab-cqyv (Tecvayli) is the first bispecific antibody that targets both the protein B-cell maturation antigen (BCMA) and CD3 (a protein on T cells). This helps bring T cells directly to the cancer cells to kill them.
• Linvoseltamab-gcpt (Lynozyfic) is a newer BCMA-directed T-cell engager.
• Elranatamab-bcmm (Elrexfio) is another BCMA-directed CD3 T-cell engager.
• Talquetamab-tgvs (Talvey) is a bispecific T-cell engager that targets GPRC5D, another protein found on myeloma cells, and CD3 on T cells.
• Selinexor (Xpovio) is a nuclear export inhibitor that disrupts how cancer cells function and grow.

New treatments are being developed through laboratory work and clinical trials. These treatment options have the goal of extending overall survival and quality of life.

Read more about anti-BCMA immunotherapies for multiple myeloma.

Join The Conversation

On MyMyelomaTeam, people share their experiences with multiple myeloma, get advice, and find support from others who understand.

How many times have you had to change your treatment plan because your myeloma became relapsed or refractory? Share your experience in the comments below.