Refractory Multiple Myeloma

Medically Reviewed by Arefa Cassoobhoy, MD, MPH on May 29, 2023
6 min read

Multiple myeloma is a cancer that affects a type of white blood cell called a plasma cell, which helps your immune system fight infections. Refractory means your cancer doesn't improve with treatment, or it stops responding to treatment.

Sometimes the first treatment you try doesn't work against your cancer. Your doctor might call this primary refractory multiple myeloma.

In other situations, your cancer might improve at first, but then gets resistant to the treatment and starts growing again. The name for this is relapsed/refractory multiple myeloma (RRMM).

When you have multiple myeloma, it's common for the cancer to come back after treatment. But thanks to new treatments, people with refractory multiple myeloma have more options, and they are living longer.

In multiple myeloma, abnormal plasma cells multiply in your bone marrow -- the soft, squishy tissue in the center of bones where new blood cells are made.

Experts don't know what causes multiple myeloma, or why it is refractory in some people. They think gene changes may make the cancer more resistant to treatment.

Refractory multiple myeloma causes the same symptoms as multiple myeloma. These symptoms either don't go away or return after treatment.

Bone pain is the most common symptom. The pain can be in your lower back or ribs. Sometimes the cancer weakens bones to the point where they fracture.

Other symptoms that your treatment isn't working are:

  • Weakness
  • Tiredness
  • Purple spots on your skin
  • Shortness of breath
  • Infections
  • Appetite loss

Once you start treatment, your doctor will do regular blood tests and imaging scans to see if your cancer has responded.

Blood tests. You'll get a complete blood count (CBC) at every check-up. This test measures the amount of red blood cells, white blood cells, and platelets in your blood. Multiple myeloma can lower the numbers of these cells.

Blood chemistry tests check levels of proteins and other substances in your blood. Multiple myeloma can cause high calcium levels and low levels of the protein albumin.

Other blood tests detect high or low levels of certain antibodies that multiple myeloma can affect. Antibodies are immune system proteins that help your body fight infections.

Urine tests. These tests check your urine for proteins and creatinine -- a waste product your body makes when it breaks down protein. High levels of certain proteins can be a sign that multiple myeloma has damaged your kidneys. For these tests, you may need to collect all of your urine for 24 hours.

Imaging tests. These tests let your doctor look inside your body to see whether your cancer has gotten smaller or if it has grown. Some tests you might get are:

  • An X-ray, which uses radiation in low doses to make images of your bones. It can show areas of bone loss from multiple myeloma.
  • An MRI, which uses powerful magnets and radio waves to make three-dimensional pictures of your bones. It shows areas where the cancer has damaged bones.
  • A CT scan, which is a powerful X-ray that makes three-dimensional images of your bones to find any areas of cancer.
  • A PET scan, which uses a radioactive sugar that your cancer cells eat up. Then a special camera takes pictures to show areas of cancer in your body.

Bone marrow tests. For these tests, your doctor removes a sample of liquid or tissue from your bone marrow. Then a lab checks your cancer's genes to predict how the cancer might grow or if it could be resistant to treatment.

When you see your doctor for follow-up visits, it's helpful to have a list of questions ready. You can also bring along a family member or friend to help you remember your questions and write down your doctor's answers.

Questions can include:

  • What follow-up tests will I need to monitor my cancer during treatment?
  • Who will I see for follow-up care?
  • How will I know if my treatment isn't working?
  • What symptoms should I watch for?
  • When should I call you?
  • If my treatment doesn't help or it stops working, what other treatments will you try?
  • What side effects could those other treatments cause?
  • Should I join a clinical trial?

There are several types of medications that can be used to treat refractory multiple myeloma. Your treatment will depend on what you have been treated with before, how your disease responded to that treatment, and how well it is likely to respond to a new treatment. These include:

Chemotherapy. It uses strong medicine to kill cancer cells or stop them from dividing. Examples include bendamustine (Bendeka), cyclophosphamide (Cytoxan), doxorubicin (Adriamycin, Rubex), and melphalan (Alkeran).

Targeted therapy:

  • Proteasome inhibitors, such as bortezomib, carfilzomib (Kyprolis) or ixazomib (Ninlaro), which slow the multiplying of myeloma cells.
  • Monoclonal antibodies such as daratumumab  (Darzalex), elotuzumab (Empliciti), and isatuximab (Sarclisa). They are human-made versions of proteins that your body makes. They attack proteins on the surface of myeloma cells to kill them directly and help your immune system fight them.
  • Nuclear Export Inhibitor. Selinexor (Xpovio) is a new kind of medication called a nuclear export inhibitor. It blocks a protein that helps myeloma cells stay alive.
  • Bi-Specific T-cell engager (BiTE).Teclistamab-cqyv (Tecvayli) is a bispecific T-cell engager that is prescribed when you have already been treated with at least four other therapies. It is a  monoclonal antibody that targets BCMA. It can attach to both a T cell and a myeloma cell at the same time causing an immune attack on the cancer cell.

Immunomodulatory drugs, such as pomalidomide (Pomalyst) and thalidomide (Thalomid) and lenalidomide (Revlimid). They block the pathways that help multiple myeloma grow.

Cellular Immunotherapy. Chimeric antigen receptor (CAR) T-cell therapy is a type of immunotherapy. Your doctor removes immune cells called T cells from your body. Those cells go to a lab, which modifies and multiplies them so they can find and attack your cancer cells. Examples include ciltacabtagene autoleucel (Carvykti) or idecabtagene vicleucel.

People with refractory multiple myeloma sometimes take two or three of these medicines at a time, along with a steroid medicine to kill more myeloma cells. Your doctor can try out different combinations of these drugs to see what works best against your cancer. If one combination doesn't help, you can switch to another one.

If your cancer doesn't respond to any of these medications, other options include:

Stem cell transplant. After you get high-dose chemotherapy, your doctors replace the blood cells that chemo destroyed with healthy cells taken from your bone marrow. You can have this treatment more than once for refractory multiple myeloma.

Researchers are studying new treatments for refractory multiple myeloma in clinical trials. Ask your doctor if a trial of a new therapy might be right for you.

As your disease changes, the treatment you're on can stop working. If the medicine you've been taking no longer helps your cancer, your doctor will switch you to something else.

Now that so many treatments for multiple myeloma are available, and even more are being studied in clinical trials, your doctor has a lot of different options to try.

It's important to reach out to others to get the emotional backing you need. Family and friends are a good place to start. You can talk to them, or ask them to help you with everyday tasks like cooking and cleaning when you don't feel well. 

Multiple myeloma support groups are another place to turn. There you'll meet other people with the same kind of cancer. They may have advice to help you manage your condition.

You can find a support group through an organization like the American Cancer Society, Multiple Myeloma Research Foundation, or the International Myeloma Foundation.

Anxiety and depression are common in people with multiple myeloma. If you feel sad or nervous, talk to your doctor. They can put you in touch with a mental health professional who can teach you strategies to help you manage.