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Refractory Multiple Myeloma

Reviewed by Brunilda Nazario, MD on April 22, 2021

What Is Refractory Multiple Myeloma?

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.

Causes

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.

Symptoms

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

Getting a Diagnosis

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.

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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.

Questions for Your Doctor

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?

Treatment

Doctors prescribe three main types of medications for refractory multiple myeloma:

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Proteasome inhibitors, such as carfilzomib (Kyprolis) or ixazomib (Ninlaro), which slow the multiplying of myeloma cells.

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

Monoclonal antibodies such as daratumumab (Darzalex) and elotuzumab (Empliciti). 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.

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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:

Chemotherapy. It uses strong medicine to kill cancer cells or stop them from dividing.

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.

Selinexor (Xpovio). This is a new kind of medication called a nuclear export inhibitor. It blocks a protein that helps myeloma cells stay alive.

Chimeric antigen receptor (CAR) T-cell therapy. This 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.

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.

What to Expect

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.

Getting Support

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.

WebMD Medical Reference

Sources

SOURCES:

American Cancer Society: "CAR T-Cell Therapy for Multiple Myeloma," "Drug Therapy for Multiple Myeloma," "Immunomodulators and Their Side Effects," "Living as a Multiple Myeloma Survivor," "Stem Cell Transplant for Multiple Myeloma," "Tests to Find Multiple Myeloma," "What is Multiple Myeloma?"

Cancer.Net: "Multiple Myeloma: Questions to Ask the Health Care Team."

Clinical Lymphoma, Myeloma & Leukemia: "Treatment Options for Triple-class Refractory Multiple Myeloma."

Drugs: "Current and New Therapeutic Strategies for Relapsed and Refractory Multiple Myeloma: An Update."

Haematologica: "Treatment of Relapsed and Refractory Multiple Myeloma."

International Myeloma Foundation: "Bone Marrow Tests," "Dexamethasone," "Distress, Fatigue, and Sexuality," "Imaging Studies," "Tests to Assess Blood Cells," "Treatments for Early Relapse," "What is Multiple Myeloma Relapse?"

Journal of Clinical Oncology: "Treatment of Multiple Myeloma: ASCO and CCO Joint Clinical Practice Guideline."

Journal of the National Comprehensive Cancer Network: "Multiple Myeloma, Version 3.2021."

Mayo Clinic: "Multiple Myeloma."

Medscape: "Multiple Myeloma."

Multiple Myeloma Research Foundation: "Clinical Trials and New Therapies for Multiple Myeloma."

National Organization for Rare Diseases: "Multiple Myeloma."

The Hematologist: "Treating Relapsed and/or Refractory Multiple Myeloma in the Complex Treatment Landscape."

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