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Most people with this blood cancer will eventually experience a relapse. New medications and drug combinations offer more options for treating relapsed multiple myeloma.

Multiple myeloma is a cancer of the plasma cells. These immune system cells make antibodies to help your body fight infections.

In the case of multiple myeloma, too many abnormal plasma cells multiply in the bone marrow. The cancer cells crowd out the healthy red blood cells that deliver oxygen to your body, white blood cells that fight infection, and platelets that help your blood clot.

The goal of treatment is to put multiple myeloma into remission. That means no longer having signs or symptoms of cancer.

Once you go into remission, your doctor may recommend maintenance therapy to help keep multiple myeloma in remission longer and prevent a relapse. Maintenance medication is typically given as a low dose over an extended period of time.

But multiple myeloma can come back, or relapse, after treatment. In fact, most people with multiple myeloma will have periods of remission followed by relapses.

A relapse that happens during treatment or soon after you stop medication is called an early relapse. In general, early relapse refers to the first, second, or third time your multiple myeloma comes back, according to the International Myeloma Foundation.

Late, or subsequent, relapse occurs after you’ve tried several different treatments, but the cancer no longer responds to them. Multiple myeloma that doesn’t respond to treatment is called refractory.

Your doctor will check you often for signs of a relapse. If your cancer does come back, there are many ways to treat it.

Read on to learn about the treatment options for relapsed multiple myeloma.

There are a number of medication options available for both early and late multiple myeloma relapse. Which treatment your doctor recommends will depend on factors such as:

  • your age and overall health
  • how fast-moving or aggressive the cancer is
  • how many relapses you’ve had
  • the length of time since your last relapse
  • which treatments you have already tried
  • your response to previous treatments

Treating relapsed multiple myeloma with drug therapy can involve changing the dose of the maintenance drug or adding other medications. Or you might switch to a different drug regimen.

If you have early relapse, you might get the same medication you’ve used previously if it worked the first time. About half of people will go into a second remission with the same medication that put them into remission before.

Often, treatment for relapsed multiple myeloma involves a combination of these medication types:

  • chemotherapy drugs
  • corticosteroids
  • immunomodulating drugs
  • proteasome inhibitors
  • monoclonal antibodies
  • bispecific T-cell engagers

Chemotherapy drugs

Chemotherapy drugs are used to kill cancer cells or slow their growth. Examples of chemotherapy drugs used for multiple myeloma include:

  • cyclophosphamide (Cytoxan)
  • doxorubicin (Adriamycin)
  • melphalan (Alkeran)

Chemotherapy can damage healthy cells in addition to cancer cells. This can cause side effects such as:

  • hair loss
  • nausea or vomiting
  • loss of appetite
  • mouth sores
  • low blood cell counts

If you’re experiencing side effects, speak with your doctor about steps you can take to help relieve them.

Corticosteroids

Corticosteroids, such as dexamethasone, are often used in combination with other multiple myeloma drugs to help fight cancer cells and reduce inflammation.

They can also be used to help reduce the nausea and vomiting associated with chemotherapy.

Corticosteroids can cause side effects, such as:

  • weight gain
  • mood changes
  • sleep problems
  • increased risk of infection

Immunomodulating drugs

Your immune system helps protect your body from invaders such as bacteria, viruses, and toxins. Immunomodulating drugs use your body’s immune system to help fight cancer cells. Examples of immunomodulating drugs used to treat multiple myeloma include:

  • lenalidomide (Revlimid)
  • pomalidomide (Pomalyst)
  • thalidomide (Thalomid)

Side effects of immunomodulating drugs may include:

  • drowsiness or fatigue
  • constipation
  • diarrhea
  • nerve damage

Proteasome inhibitors

A proteasome is an enzyme complex found in cells. It helps break down proteins that are damaged or no longer needed. A proteasome inhibitor blocks this process from happening in myeloma cells. Proteins build up in the cell, causing it to die.

Proteasome inhibitors for multiple myeloma include:

  • bortezomib (Velcade)
  • carfilzomib (Kyprolis)
  • ixazomib (Ninlaro)

Side effects of proteasome inhibitors include

  • nausea and vomiting
  • diarrhea
  • constipation
  • low blood platelet count
  • nerve damage

Monoclonal antibodies

Monoclonal antibodies target specific proteins on the surface of myeloma cells. They attach to these proteins, either killing the cancer cell or preventing it from growing.

Monoclonal antibodies for multiple myeloma include:

  • daratumumab (Darzalex)
  • elotuzumab (Empliciti)
  • Isatuximab (Sarclisa)

They are typically given as an infusion into a vein. Some people may have a reaction to the infusion that involves:

  • coughing
  • wheezing
  • trouble breathing
  • runny or stuffy nose
  • dizziness
  • headache

Other side effects may include:

  • fatigue
  • fever
  • nausea
  • diarrhea or constipation

Bispecific T-cell engagers

Bispecific T-cell engagers are newer antibodies that attach to two separate targets.

For instance, one part of bispecific T-cell engager may attach to an immune cell while the other attaches to a protein on a cancer cell. This brings the two together and helps the immune system fight off cancer cells.

Options used for multiple myeloma may include:

  • elrenatamab (Elrexfio)
  • talquetamab (Talvey)
  • teclistamab (Tecvayli)

Bispecific T-cell engagers can be given through an IV or as an injection. They may cause side effects such as:

  • fever
  • fatigue
  • headache
  • nausea
  • diarrhea
  • rash
  • muscle or joint pain
  • low blood cell counts

Drug combinations

Common drug combinations for relapsed multiple myeloma include:

  • Velcade, Revlimid, and dexamethasone
  • Kyprolis and dexamethasone
  • Darzalex, Velcade, and dexamethasone
  • Darzalex Faspro, Pomalyst, and dexamethasone
  • Darzalex, Revlimid, and dexamethasone
  • Empliciti, Revlimid, dexamethasone
  • Ninlaro, Revlimid, and dexamethasone
  • Kyprolis, Revlimid and dexamethasone
  • Kyprolis, daratumumab and hyaluronidase-fihj (Darzalex Faspro), and dexamethasone
  • Pomalyst, Empliciti, and dexamethasone
  • Pomalyst, Kyprolis, and dexamethasone
  • Pomalyst, Velcade, and dexamethasone

A stem cell transplant may be an option for treating relapsed multiple myeloma if you:

  • haven’t had a stem cell transplant before
  • had a stem cell transplant that put you into remission for 2 to 3 years

Stem cells are the early cells that grow into new red blood cells, white blood cells, and platelets. A stem cell transplant replaces the cancer cells in your bone marrow with healthy stem cells.

To start the process, healthy stem cells are collected from your own body and stored until they are needed for transplant. This is called an autologous stem cell transplant.

Then, you’ll get high dose chemotherapy to kill the multiple myeloma cells in your bone marrow. Afterward, you’ll receive your stored stem cells through a vein. Those transplanted stem cells will develop into healthy new blood cells.

Chimeric antigen receptor (CAR) T-cell therapy is a type of immune therapy. This treatment genetically engineers your own immune cells, called T cells, in a lab to help them find and kill cancer cells.

To begin this process, a doctor will draw your blood through an IV. The blood is run through a machine that removes the T cells during a process called leukapheresis. The remaining blood goes back into your body.

The removed T cells are frozen and genetically altered to add CARs to their surface. CARs are proteins that help T cells recognize and attach to cancer cells.

More CAR T cells are then created in the lab. When there are enough, they are thawed and infused back into your body.

CAR T-cell therapy for multiple myeloma targets a protein called B-cell maturation antigen (BCMA). BCMA is on the surface of cancerous plasma cells but not healthy cells. The modified T cells lock onto the plasma cells and destroy them.

This treatment is approved for multiple myeloma that has relapsed or that hasn’t responded to at least four other therapies. Two CAR T-cell therapies are approved for multiple myeloma:

  • ciltacabtagene autoleucel (Carvykti)
  • idecabtagene vicleucel (Abecma)

CAR T-cell therapy can cause side effects such as:

  • chills
  • cough
  • cytokine release syndrome (an immune system reaction that causes body-wide inflammation)
  • diarrhea
  • fever
  • hypogammaglobulinemia (a drop in antibodies that protect against germs)
  • infections
  • low blood cell counts
  • muscle and bone pain
  • nausea
  • tiredness

Every medication that’s approved for multiple myeloma had to go through a clinical trial. These studies test the safety and effectiveness of new medications and drug combinations.

Joining a clinical trial could give you access to a promising new multiple myeloma treatment. An experimental drug might be an option if your cancer hasn’t responded to many approved treatments. If you’re interested in participating in a trial, ask the doctor who treats your multiple myeloma or search for one in your area.

Below are some of the most common questions about relapsed multiple myeloma treatments.

What are the treatments for early relapsed multiple myeloma?

Often, treatment combines medications from three groups: proteasome inhibitors, immunomodulating drugs, and monoclonal antibodies.

If you have certain gene changes that make your multiple myeloma high risk, it’s important to get a treatment that works quickly.

What is the best treatment for relapsed multiple myeloma?

The best treatment is different for each person. Your myeloma specialist will find the right treatment for you based on your health, what treatments you had before, and how well they worked.

You may get the same treatment as you did when you were first diagnosed or different medications.

What is the outlook for relapsed refractory multiple myeloma?

Your outlook depends on the cancer stage, how aggressive the cancer is, and how well you respond to treatment. In general, the outlook is worse for relapsed or refractory multiple myeloma.

However, many new therapies are improving the outlook for hard-to-treat multiple myeloma.

Most people with multiple myeloma experience periods of remission followed by relapse. There are a number of treatment options for multiple myeloma that has come back, including medications or combinations of medications, CAR T-cell therapy, stem cell therapy, and clinical trials.

The type of treatment you’ll have depends on factors such as how many relapses you’ve had, which treatments you’ve tried, and how you’ve responded to previous treatments. Talk with your doctor about your treatment options, how they work, and what side effects they may cause.