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Sometimes multiple myeloma doesn't respond well to the first treatments, such as drug therapy or stem cell transplant. Or a treatment that was helpful for a while may stop working. This is known as relapsed/refractory multiple myeloma, or RRMM.

Your doctor has many treatment options if your disease returns. Here are some details on those choices, and questions you should ask so you can make the best decisions.

What Is Multiple Myeloma and How Is It Treated?

Multiple myeloma (MM) is cancer of the plasma cells, a type of white blood cell in your bone marrow. These cells make the antibodies that help your body fight infections. But when you have MM, these cells are not normal and grow out of control. That can cause bone pain, fractures, and a lack of healthy red and white blood cells. Your kidneys may also be damaged because of the abnormal proteins these cancer cells produce.

There are many treatments for multiple myeloma, including stem cell (bone marrow) transplants, chemotherapy drugs, medications that target cancer cells (but aren’t chemo), and corticosteroids. More treatment options have led to improved survival over the past 30 years. But because these therapies don’t often cure the cancer completely, many people will need several different treatments during their illness.

So it’s important to talk with your doctor about the best decisions for your symptoms and your best quality of life.

How Is RRMM Diagnosed and Treated?

RRMM is diagnosed when a person responds poorly to MM treatment, or if that treatment has stopped working within 60 days.

Before you begin any new therapy, your doctor will complete a thorough exam. This may include:

  • Full medical history, including adverse effects from each drug used in your first round of treatment
  • Physical exam
  • Restaging of your disease with scans (CT, PET, MRI) to see if there has been any further spread of your cancer since your original diagnosis.
  • Review of your symptoms to see if you qualify for a clinical trial

After a relapse, your doctor can choose from several drugs and combinations of drugs to treat you. These include:

  • Antibodies that target myeloma cells (belantamab mafodotin, daratumumab, elotuzumab, isatuximab)
  • Chemotherapy drugs that kill cancer cells (cyclophosphamide, melphalan)
  • Immunomodulatory drugs that help your immune system fight cancer better (lenalidomide, pomalidomide, thalidomide)
  • Nuclear export inhibitor that keeps proteins that stop tumors in the cell nucleus (selinexor)
  • Proteasome inhibitors that allow proteins to build up a lot and kill the myeloma cells (bortezomib, carfilzomib, ixazomib)
  • Steroids that can help lower inflammation (dexamethasone)

Usually you will need two or three of these drugs at a time. This combination therapy can be effective for a long time and may reduce the chance that the treatment will be harmful.

The right combination of these drugs depends on a lot of things:

  • Drugs already received
  • Bad effects
  • Other health problems you have
  • Expected ability to tolerate the new drugs

What Are the Goals of Your RRMM Treatment?

Your doctor will think about factors such as your age, frailty, and your other health issues with these goals:

  • Prevent new damage to your organs
  • Relieve your disease symptoms
  • Go into a lasting disease remission, a period when your condition is not as intense

Questions to Ask Your Doctor: Don’t Be Shy

All those treatments can sound confusing, even a little scary. It’s important to get all the information you can so you understand the benefits and the risks. Some questions to ask:

  • What are my treatment options? How can each one help?
  • What follow-up tests will I need?
  • What side effects should I watch out for?
  • How will we know if the new treatment is working?
  • Could I benefit from being part of a clinical trial? (Clinical trials are carefully designed studies to see how new treatments – or combinations of current treatments – may work.)

Communication Is Crucial for Your Care

Concerns about your treatment are never silly nor a waste of your doctor’s time. These tips might help you prepare to talk with your oncologist:

  • Keep a list of questions and bring it to your appointment.
  • If you’re confused, ask your doctor to explain a procedure in a different or simpler way to make sure you understand.
  • Take a family member or friend with you. A loved one can listen, take notes, record the conversation, and also ask questions.
  • Talk with your doctor about any advice you have found on your own. It could be helpful, but it may be wrong or not apply to your symptoms.
  • Don’t be afraid to ask about the costs of your treatment. Your doctor and cancer care team can help find payment options.
  • Before you leave your appointment, get the name and number of a staff member to contact if you have more questions.

Good communication with your doctors and other health care team members can pay off in many ways for you and for your family. Some of those positive results:

  • You feel more in control of your care.
  • You’ll stay more informed.
  • It’s more likely you will follow through with treatment.
  • There’s a greater chance you’ll join a clinical trial.
  • You’re better able to make the change from cancer treatment to palliative care (which focuses on providing relief from your symptoms and stress, and improving your quality of life).

Choosing a Treatment Plan for RRMM

In putting together a RRMM plan, your doctor will review the results of your previous treatments, any bad effects from them, any other health issues you have that may cause complications, plus a look at how your body is expected to respond to any new treatment.

There are many drugs to choose from, and all can have side effects. That’s why it is so important to communicate with your doctor about how your body is responding to the treatment. That’ll help them figure out if any adjustments are needed. Talk with your doctor about:

  • How you should prepare for your new treatment
  • Whether a family member can be with you during treatment
  • What side effects you might expect
  • What problems should you watch for after your treatment and when you should call a doctor

What’s Ahead?

Life expectancy is increasing because of many new therapies for RRMM.  While there is no cure, continuous therapy from first relapse through the disease progression brings the possibility that MM can be managed long-term as a chronic illness.

Show Sources

Photo Credit: Tetra Images / Getty Images


UpToDate: “Patient education: Multiple myeloma treatment (Beyond the Basics).”

Hematology: “Management of multiple myeloma in the relapsed/ refracted patient.”

Hematology, ASH Education Program: “Management of multiple myeloma in the relapsed/refractory patient.”

Haematologica:  “Treatment of relapsed and refractory multiple myeloma.”

Mayo Clinic Proceedings: “Therapy for Relapsed Multiple Myeloma.”

Multiple Myeloma Research Foundation: “Proteasome inhibitors.”

Targeted Oncology: “Targeting Nuclear Export Proteins in Multiple Myeloma Therapy.”

Center to Advance Palliative Care: “About Palliative Care.”

National Cancer Institute: “Communication in Cancer Care (PDQ)-Patient Version.”