Multiple myeloma is a kind of blood cancer that starts in white blood cells called plasma cells. Cancerous plasma cells grow out of control in your bone marrow, so there’s not enough room for healthy blood cells. They also release a defective protein that can cause bone and kidney damage.
You may have responded well to your treatment at first. But over time, the disease is able to change and become resistant to the drugs most often used to fight it. When multiple myeloma comes back after treatment, that’s called a relapse. When treatment doesn’t work, the disease is called refractory.
Relapsed/refractory multiple myeloma (RRMM) is a challenge to treat. There’s no strategy that works for everyone. Doctors are constantly trying out new drugs and new combinations of drugs to get past drug resistance and increase the amount of time you’re healthy before the disease comes back.
Taking part in a clinical trial may be a good option to get you access to cutting-edge treatment.
Should You Consider a Clinical Trial?
Treatment for relapsed/refractory multiple myeloma is very personalized. It depends on which drugs you’ve had before and how well they worked for you. Your doctor also has to consider how healthy you are overall and whether you can handle possible side effects. Several treatment regimens are approved for RRMM that include a combination of drugs from these categories:
- Chemotherapy – drugs that kill cancer cells
- Immunomodulators – drugs that help your immune system fight cancer
- Monoclonal antibodies – target myeloma cells
- Nuclear export inhibitor – keeps proteins that prevent tumors in the cell nucleus
- Proteasome inhibitors – allow proteins to build up and kill myeloma cells
- Steroids – help reduce inflammation but can only be used for a short time
Each person’s cancer responds differently to individual drugs. Some never work. Others work for a while, then stop. So finding new treatments is especially important in multiple myeloma.
If you’ve tried different drug combinations and your multiple myeloma comes back, talk to your doctor about whether you should consider a clinical trial. They can tell you what kind of new treatment might be promising. And they can steer you to trials in your area.
You can also find a clinical trial yourself:
- Search by disease and location at government websites including clinicaltrials.gov and cancer.gov.
- Other organizations that let you search for clinical trials on their websites include The Center for Information and Study on Clinical Research Participation (ciscrp.org) and CenterWatch.com.
- Check the websites of hospitals, medical schools, or cancer centers in your area. They may list trials they’re doing or tell you how to get in touch with their research departments.
The Leukemia and Lymphoma Society has a service that gives you guidance on finding and taking part in a clinical trial at lls.org.
New and Emerging Treatments
To get past drug resistance, scientists are developing new drugs in the same categories as those already approved to treat multiple myeloma. They’re also testing new combinations of three and even four of these drugs. And they’re looking at different kinds of drugs that attack multiple myeloma in new ways. Here are some of the most promising areas of research.
Targeted therapy: Chemotherapy kills fast-growing cells. That includes cancer but also many normal cells. Targeted therapy looks for weaknesses unique to cancer cells that can be taken advantage of to kill them without harming healthy cells. Drugs under development include:
- Proteasome inhibitors. These allow molecular “garbage” to build up inside multiple myeloma cells until they die. You’ve probably had at least one of these drugs. Bortezomib, carfilzomib, and ixazomib are approved to treat RRMM. But it can become resistant to them. Researchers are trying these drugs in different combinations and testing new ones.
- Antibody-drug conjugate. This is a new kind of treatment using an antibody that attaches itself to a tumor cell and delivers a drug that kills it. The drug belantamab mafodotin-blmf was recently approved for people with RRMM who’ve tried at least four other treatments. It finds a receptor called a B cell maturation antigen (BCMA) that’s plentiful in myeloma cells and almost nowhere else. Other similar drugs are being tested.
- BCL2 and MCL1 inhibitors. BLC2 and LCL1 are proteins that allow damaged myeloma cells to repair themselves. Drugs are being tested that block the action of these proteins, either alone or in combination with approved treatments.
Immunotherapy: This type of treatment harnesses your body’s own disease-fighting system to identify and attack cancer cells. A number of new therapies are being explored:
- Immunomodulators. Most of the drug combinations for treating RRMM include a drug that helps your immune system fight the cancer, either lenalidomide or pomalidomide. New kinds of immunomodulators are being tested for people who stop responding to these.
- T-cell therapy. Two recently approved treatments for RRMM use what are called chimeric antigen receptor (CAR) T cells. These are your own immune cells that have been removed, modified to better recognize and attack myeloma cells, then put back into your blood. The new treatments look for the BCMA protein. More of those are in the pipeline, along with others that use different receptor targets.
- Bispecific T-cell engagers (BiTE). This kind of drug contains an antibody that attaches to both a receptor on a multiple myeloma cell and a protein on an immune cell. That causes the immune cell to attack the cancer cell. Several BiTEs are being tested.
- Checkpoint inhibitors. Checkpoints tell your immune system when to fight and when to back off. Cancer cells can trick these checkpoints into applying the brakes and letting them live. Checkpoint inhibitors put your immune system back to work fighting your cancer. Researchers are developing a number of these drugs.
What to Expect From a Clinical Trial
Once you and your doctor have found a promising experimental treatment, find out everything you can about how the study is being done and what researchers hope to learn. Whoever is sponsoring the trial – often a drug company – may have information on their website. Or you can contact them directly.
In general, here’s what you can expect from a clinical trial:
- You’ll have an interview with someone at the study to make sure you qualify. You may need to be a certain age or have a certain stage of cancer. Some trials want people who’ve already tried certain treatments.
- Before you enroll, you’ll get detailed information about the study, including the risks and possible benefits of the new treatment, and any rules you’re expected to follow. The people running the study want to make sure you understand exactly what you’re signing up for.
- Find out what costs there may be for tests and treatments. Usually, these are covered either by your health insurance or the study itself. You might even get paid by the study for expenses like travel.
- After you enroll, you’ll give details about your medical history. You may have a physical exam and blood work or imaging tests.
- During the study, you’ll get whatever treatment is being tested, or you may be in a control group to see whether the new treatment is better than the standard treatment. You’ll also have checkups and tests to see how well the treatment is working and how you’re doing.
- Taking part in a clinical trial is voluntary, and you’re free to quit at any time, for any reason.
If you don’t qualify for a clinical trial, you may still be able to get the newest treatments for relapsed/refractory multiple myeloma. Expanded access or compassionate use programs sometimes offer unapproved medications to people who are very sick and have no other options. Check with your doctor.
Photo Credit: shironosov / Getty Images
UpToDate: “Patient education: Multiple myeloma treatment (Beyond the Basics).”
American Society of Clinical Oncology: “Multiple Myeloma: Introduction,” “Multiple Myeloma: Types of Treatment,” “Finding a Clinical Trial,” “Multiple Myeloma: Latest Research,” “About Clinical Trials,” “Health Insurance Coverage of Clinical Trials.”
Leukemia & Lymphoma Society: “Clinical Trials,” “Refractory and Relapsed,” “Clinical Trial Support Center (CTSC).”
Journal of Clinical Pathways: “Clinical Pathways Updates in Multiple Myeloma: New and Expected Treatments for Refractory and Resistant Multiple Myeloma.”
Journal of the National Comprehensive Cancer Network: “Updates in the Treatment of Multiple Myeloma.”
National Cancer Institute: “Find NCI-Supported Clinical Trials,” “Targeted Therapy to Treat Cancer,” “Immune Checkpoint Inhibitors.”
The Center for Information and Study on Clinical Research Participation: “Search Clinical Trials.”
Cancers: “Emerging Therapeutic Strategies to Overcome Drug Resistance in Multiple Myeloma.”
Journal of Hematology & Oncology: “BCMA-targeted immunotherapy for multiple myeloma.”
American Cancer Society: “Drug Therapy for Multiple Myeloma,” “CAR T-cell Therapy for Multiple Myeloma,” “Being in a Clinical Trial,” “Deciding Whether to Be Part of a Clinical Trial.”
Blood and Lymphatic Cancer: Targets and Therapy: “BCL2 Family Inhibitors in the Biology and Treatment of Multiple Myeloma.”
Memorial Sloan Kettering Cancer Center: “Multiple Myeloma: Improved Prognosis with the Latest Treatments.”