Multiple myeloma is a form of blood cancer that develops when plasma cells (a type of white blood cell) begin to grow and divide uncontrollably. After you receive a multiple myeloma diagnosis, first-line therapies are used to control the cancer and help you achieve remission. However, after being in remission, most people will relapse, which means that their cancer has returned.
Once you relapse, your hematologist/oncologist (a doctor specializing in blood cancer) will develop a new treatment plan to help you achieve remission again. Most people experience multiple relapses, depending on their specific multiple myeloma case. Knowing what to expect if and when your myeloma relapses can help you prepare for future treatments.
The International Myeloma Foundation defines a multiple myeloma relapse as “the reappearance of signs and symptoms of a disease after a period of improvement.” Relapses occur when some myeloma cells remain after treatment, known as minimal residual disease (MRD). These leftover cells can continue to grow and divide. The goal of treatment is to reduce MRD as much as possible. Although myeloma treatments are generally effective and kill off most myeloma cells, just a few surviving cells can result in an eventual relapse.
Relapsing multiple myeloma is common — in a 2016 study, 16 percent of people with multiple myeloma relapsed within one year. After about four years, almost 66 percent of participants had experienced a relapse.
Sometimes a multiple myeloma relapse is diagnosed when you notice new symptoms such as bone pain. In most cases, your hematologist/oncologist may suspect a relapse after performing blood work or imaging tests. A relapse is diagnosed based on test results that show changes in blood globulin levels, formation of bone lesions, and an increase in plasma cells in the bone marrow.
MRD testing can also be done after treatment to monitor remission. This method uses next-generation sequencing (technologies to look for genetic changes) or flow cytometry to look for myeloma cells in the bone marrow. Flow cytometry uses special antibodies that bind to proteins on the surface of cells to identify them as myeloma cells. If MRD can be detected after treatment is complete, a relapse may occur sooner rather than later.
Most people with multiple myeloma respond well to their first-line therapy (the first regimen used to treat their cancer) for around two or three years but eventually have a relapse. After the initial relapse, you can expect to undergo periods of response to new medications followed by subsequent relapses.
First or second relapses may be considered early relapses if they occur soon after ending initial therapy. A small number of people relapse within a year after initial treatment. A very early relapse may develop if you do not respond well to initial therapy, have high-risk disease (known as primary refractory disease), or relapse during maintenance therapy.
After your first relapse, your hematologist/oncologist will reevaluate your treatment plan. Several factors go into changing a plan or developing a new one, including:
If you previously had an autologous bone marrow transplant and then several years of remission, your hematologist/oncologist may recommend another transplant. They will discuss the pros and cons of this procedure with you and whether it’s worth trying again. They may also adjust your maintenance therapy, such as adding dexamethasone combined with lenalidomide (Revlimid).
In some circumstances, your hematologist/oncologist may recommend restarting your original therapy, which led to remission. This is typically done if remission lasted for six months to one year after treatment ended. Reintroducing initial therapy is successful around 50 percent of the time and leads to remission, especially in people who were in remission for at least a year.
If you get a new treatment plan, you may start one of many classes of drugs, including alkylating agents, immunomodulatory drugs, proteasome inhibitors, and monoclonal antibodies. Some of these medications are approved as first-line therapies and can also be used after early relapses. Others, including the alkylating agent cyclophosphamide (Cytoxan) and the immunomodulatory drugs lenalidomide and thalidomide (Thalidomid), are approved for use only after other therapies have failed.
Proteasome inhibitors that can be used if earlier treatments didn’t work include:
Monoclonal antibodies may be another option. These include:
The U.S. Food and Drug Administration (FDA) also has approved the following drug combinations for treating early relapsed multiple myeloma:
Many people will continue to relapse after new treatments, undergoing several periods of remission and then relapse. With each new relapse, your hematologist/oncologist will change your treatment plan to include new drugs. Eventually, this leads to myeloma cells that become increasingly resistant to more drug combinations. This may make it more difficult to treat multiple myeloma relapses.
Your hematologist/oncologist may use genetic testing to look at the mutations in your myeloma cells. This test may reveal changes in certain genes that can be targeted with treatments, making them more effective. Genetic testing can also show if you have high-risk multiple myeloma, a more aggressive form of the disease. Whether you have high-risk multiple myeloma will help your doctor determine which treatments may be best for you. Staging tests that can show the extent of your cancer include blood work, urine tests, imaging studies, and a bone marrow biopsy.
Several drugs can be used to treat later relapses. Many people with multiple myeloma eventually become resistant to immunomodulatory drugs, proteasome inhibitors, and monoclonal antibodies, so they are treated with new classes of therapies. Specifically, these therapies are approved for treating people with multiple myeloma that relapsed after at least four lines of therapy.
One drug class that is used to overcome resistance includes antibodies that target B-cell maturation antigen (BCMA). These antibodies bind to the BCMA protein on the outside of myeloma cells. Three BCMA-targeted antibodies have been approved by the FDA for treating relapsed multiple myeloma:
These latter two are a type of treatment known as chimeric antigen receptor T-cell therapy — or CAR T-cell therapy — which involves teaching the immune system’s T cells to attack myeloma cells.
For people who have had multiple relapses and generally exhausted their treatment options, clinical trials may be a good option. These studies test novel agents (new treatments) that are not yet FDA-approved for treating multiple myeloma but show promise in being effective.
Clinical trials may also use new combinations of already-approved drugs that haven’t yet been tested together. Options currently being investigated include:
If you’re interested in learning more about clinical trials for relapsing multiple myeloma, talk to your hematologist/oncologist. They will be able to recommend studies for which you may be eligible and discuss the benefits and risks of clinical trials.
In general, the five-year survival rate for multiple myeloma is 55 percent, and around 31.6 percent of people are alive 10 years after their initial diagnosis. The time from the end of treatment to the first relapse strongly predicts survival. For example, one study found that people who initially relapsed within one year of treatment had, on average, a survival rate of just under two years. Those who relapsed later had a survival rate of approximately 10 years.
As research continues, myeloma treatments continue to improve overall survival rates and quality of life. Talk to your doctor about what to expect with a multiple myeloma relapse and what treatment options may work best for your individual condition.
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