Multiple Myeloma: Types of Treatment

Approved by the Cancer.Net Editorial Board, 05/2020

ON THIS PAGE: You will learn about the different types of treatments doctors use to treat people with multiple myeloma. Use the menu to see other pages.

This section explains the types of treatments that are the standard of care for multiple myeloma. “Standard of care” means the best treatments known. When making treatment plan decisions, you are also encouraged to consider clinical trials as an option. A clinical trial is a research study that tests a new approach to treatment. Doctors want to learn if it is safe, effective, and possibly better than the standard treatment. Clinical trials can test a new drug, a new combination of standard treatments, or new doses of standard drugs or other treatments. Clinical trials are an option to consider for treatment and care for all stages of cancer. Your doctor can help you consider all your treatment options. Research for new myeloma treatments is very active, and many clinical trials are offered. Learn more about clinical trials in the About Clinical Trials and Latest Research sections of this guide.

Treatment overview

In cancer care, different types of doctors often work together to create a patient’s overall treatment plan that combines different types of treatments. This is called a multidisciplinary team. Cancer care teams also include a variety of other health care professionals, including physician assistants, nurse practitioners, oncology nurses, oncology social workers, pharmacists, counselors, dietitians, and others.

The treatment of multiple myeloma depends on whether the patient is experiencing symptoms (see Stages) and the patient’s overall health. In many cases, a team of doctors will work with the patient to determine the best treatment plan. The goals of treatment are to eliminate myeloma cells, control tumor growth, control pain, and allow patients to have an active life. While there is no cure for multiple myeloma, the cancer can be managed successfully in many patients for years.

Descriptions of common types of treatments used for multiple myeloma are listed below. Your care plan may also include treatment for symptoms and side effects, an important part of cancer care.

The information below is divided into treatment options for people without symptoms and for people with symptoms. In addition, treatment options may depend on whether the patient is newly diagnosed with myeloma or is experiencing a recurrence of the disease. Take time to learn about all of your treatment options, including clinical trials, and be sure to ask questions about things that are unclear. Also, talk about the goals of each treatment with your doctor and what you can expect while receiving the treatment. These types of talks are called “shared decision making.” Shared decision making is when you and your doctors work together to choose treatments that fit the goals of your care. Shared decision making is particularly important for multiple myeloma because there are different treatment options. Learn more about making treatment decisions.

Active surveillance for people without symptoms

People with early-stage myeloma and no symptoms, called SMM (see Stages), may simply be closely monitored by the doctor through checkups. This approach is called active surveillance or watchful waiting. As noted previously, if there is evidence of bone thinning, or osteoporosis, periodic infusions of bisphosphonates to reverse this process may be recommended. There are also clinical protocols, or processes, used to evaluate whether using medications called targeted therapy (see below) or immunotherapy (see below and Latest Research) can prevent or delay myeloma from developing into a disease that requires treatment. If symptoms appear, then active treatment starts. Two clinical trials in high-risk SMM have shown that early treatment can slow the progression to myeloma with symptoms for some patients, but whether this helps people live longer is not known.

Overview of treatment options for patients with symptoms

Treatment for people with symptomatic myeloma includes both treatment to control the disease as well as supportive care to improve quality of life, such as by relieving symptoms and maintaining good nutrition. Disease-directed treatment typically includes drug therapy, such as targeted therapy and/or chemotherapy, with or without steroids. Bone marrow/stem cell transplantation may be an option. Other types of treatments, such as radiation therapy and surgery, are used in specific circumstances. Each type of treatment is described below.

The treatment plan includes different phases.

  • Induction therapy for rapid control of cancer and to help relieve symptoms.

  • Consolidation with more chemotherapy or bone marrow/stem cell transplant.

  • Maintenance therapy over a prolonged period to prevent cancer recurrence.

Therapies using medication

Systemic therapy is the use of medication to destroy cancer cells. This type of medication is given through the bloodstream to reach cancer cells throughout the body. Systemic therapies are generally prescribed by a medical oncologist, a doctor who specializes in treating cancer with medication.

Common ways to give systemic therapies include an intravenous (IV) tube placed into a vein using a needle or in a pill or capsule that is swallowed (orally).

The types of systemic therapies used for multiple myeloma include:

  • Chemotherapy

  • Targeted therapy

  • Immunomodulatory drugs

  • Immunotherapy

  • Steroids

  • Bone-modifying drugs

Each of these types of therapies are discussed below in more detail. A person usually receives a combination of systemic therapies given at the same time. They can also be given as part of a treatment plan that includes surgery and/or radiation therapy.

Combination regimens are an important part of the treatment of multiple myeloma. Combining different treatment effects from different types of drugs – such as a combination of an immunomodulatory drug, a proteasome inhibitor, and a steroid – can be an effective way of managing the disease. In addition, other targeted treatments may be added, depending on the individual's specific situation.

The medications used to treat cancer are continually being evaluated. Talking with your doctor is often the best way to learn about the medications prescribed for you, their purpose, and their potential side effects or interactions with other medications. It is also important to let your doctor know if you are taking any other prescription or over-the-counter medications or supplements. Herbs, supplements, and other drugs can interact with cancer medications. Learn more about your prescriptions by using searchable drug databases.

Chemotherapy

Chemotherapy is the use of drugs to destroy cancer cells, usually by keeping the cancer cells from growing, dividing, and making more cells.

A chemotherapy regimen (schedule) usually consists of a specific number of cycles given over a set period of time. A patient usually receives combinations of different drugs at the same time.

Combination chemotherapy has been used successfully for the treatment of myeloma. These drugs include cyclophosphamide (available as a generic drug), doxorubicin (available as a generic drug), melphalan (Alkeran, Evomela), etoposide (available as a generic drug), cisplatin (available as a generic drug), carmustine (BiCNU), and bendamustine (Bendeka). Chemotherapy drugs like these may be used in certain situations. For example, melphalan is most commonly used when a bone marrow transplantation is part of the treatment plan. A high dose of melphalan is used to suppress the myeloma for a long time, and the patient's own bone marrow cells are used to recover from this treatment.

It may also be recommended to combine chemotherapy with other types of treatment, including targeted therapies (see below) or steroids (see below). For instance, the combination of melphalan, the steroid prednisone (multiple brand names), and a targeted therapy called bortezomib (Velcade; see below) is approved by the U.S. Food and Drug Administration (FDA) for the initial treatment of multiple myeloma. This is because this combination often helps people live longer when compared with the combination of melphalan and prednisone.

The side effects of chemotherapy depend on the individual and the dose used, but they can include fatigue, risk of infection, nausea and vomiting, hair loss, loss of appetite, and diarrhea or constipation. Other side effects include peripheral neuropathy (tingling or numbness in feet or hands), blood clotting problems, and low blood counts. These side effects usually go away once treatment is finished. Occasionally an allergic reaction such as skin rash may occur and the drug may have to be stopped.

The length of chemotherapy treatment varies from patient to patient and is usually given until the myeloma is well controlled.

Learn more about the basics of chemotherapy.

Targeted therapy

Targeted therapy is a treatment that targets the cancer’s specific genes, proteins, or the tissue environment that contributes to cancer growth and survival. This type of treatment blocks the growth and spread of cancer cells and limits damage to healthy cells. In recent years, targeted treatment, sometimes called novel therapy, has proven to be increasingly successful at controlling myeloma and improving prognosis. Researchers continue to investigate new and evolving drugs for this disease in clinical trials.

Not all tumors have the same targets. To find the most effective treatment, your doctor may run tests on cancer cells to identify genes, proteins, and other factors. This helps doctors better match each patient with the most effective treatment whenever possible. In addition, research studies continue to find out more about specific molecular targets and new treatments directed at them. Learn more about the basics of targeted treatments.

Targeted therapy for multiple myeloma includes:

  • Proteasome inhibitors. Bortezomib (Velcade), carfilzomib (Kyprolis), and ixazomib (Ninlaro) are classified as proteasome inhibitors. They target specific enzymes called proteasomes that digest proteins in the cells. Because myeloma cells produce a lot of proteins (see the Introduction), they are particularly vulnerable to this type of drug. Bortezomib is approved to treat newly diagnosed patients. The drug also treats recurrent myeloma, as do carfilzomib and ixazomib.

  • Histone deacetylase inhibitors. Panobinostat (Farydak), an inhibitor of the enzyme histone deacetylase (HDAC), also treats recurrent myeloma. HDACs help keep the DNA tightly coiled, while panobinostat helps uncoil the DNA and activate genes that stop or slow the growth of cancer cells.

  • Monoclonal antibodies. Elotuzumab (Empliciti) and daratumumab (Darzalex) are monoclonal antibodies that bind to myeloma cells and label them for removal by the person's own immune system. A drug combination of daratumumab and hyaluronidase-fihj (Darzalex Faspro) may also be used to treat multiple myeloma. This combination is given under the skin of the abdomen and is quicker than when it is given by injection through a vein.

  • Nuclear export inhibitors. Selinexor (Xpovio) is a targeted therapy that is given in combination with dexamethasone, a steroid available as a generic drug. This combination is used to treat adults with multiple myeloma that has come back after at least 4 previous treatments.

Targeted therapies may also be used in combination with chemotherapy (see above), immunomodulatory drugs, or steroid medications (see below), because certain combinations of drugs can sometimes have a better effect than a single drug. For example, the drugs lenalidomide, bortezomib, and dexamethasone, as well as bortezomib, cyclophosphamide, and dexamethasone, are offered in combination as initial treatment. Clinical trials are exploring whether the combination of lenalidomide, bortezomib, and dexamethasone may be as effective as lenalidomide, bortezomib, and dexamethasone followed by bone marrow/stem cell transplant (see below).

Thalidomide (Synovir, Thalomid), lenalidomide, and bortezomib can also be effectively used as maintenance therapy to extend the disease's response to the initial therapy or after a bone marrow/stem cell transplant. However, the decision to undergo a transplant is complex and should be discussed carefully with your doctor.

Research has shown that maintenance therapy (the ongoing use of a drug) with lenalidomide and/or bortezomib increases how long patients survive and extends how long they live without active myeloma. Maintenance therapy has to be used with some caution, although recent studies have shown significant improvement with survival using this approach. Find out more about the basics of maintenance therapy.

Immunomodulatory drugs

Thalidomide, lenalidomide (Revlimid), and pomalidomide (Pomalyst) are classified as immunomodulatory drugs, which stimulate the immune system. These drugs also keep new blood vessels from forming and feeding myeloma cells. Thalidomide and lenalidomide are approved to treat newly diagnosed patients. Lenalidomide and pomalidomide are also effective for treating recurrent myeloma.

Immunotherapy

Immunotherapy, also called biologic therapy, is designed to boost the body's natural defenses to fight the cancer. It uses materials made either by the body or in a laboratory to improve, target, or restore immune system function.

An immunotherapy called isatuximab-irfc (Sarclisa) is approved by the FDA for the treatment of adults with multiple myeloma who have received 2 previous treatments. Isatuximab-irfc is given in combination with pomalidomide and dexamethasone.

Different types of immunotherapy can cause different side effects. Common side effects include skin reactions, flu-like symptoms, diarrhea, and weight changes. Talk with your doctor about possible side effects for the immunotherapy recommended for you. Learn more about the basics of immunotherapy.

Steroids

Steroids, such as prednisone and dexamethasone, may be given alone or at the same time as other drug therapy, such as with targeted novel therapy or chemotherapy (see above). Steroids are very effective at reducing the burden of plasma cells, but this effect is only temporary.

For example, lenalidomide and dexamethasone as induction and maintenance therapy is recommended for those who are not able to have stem cell transplantation. Adding bortezomib to this combination has recently been shown to be effective in a clinical trial. People with myeloma also receive monthly infusions of bisphosphonate therapy, which are drugs that help to prevent bone disease related to myeloma from getting worse.

Bone-modifying drugs

Most people with myeloma receive treatment with bone-modifying drugs. These drugs help strengthen the bone and reduce bone pain and the risk of fractures.

There are 2 types of bone-modifying drugs available for treating bone loss from multiple myeloma. The choice of drugs depends on your overall health and your individual risk of side effects.

  • Bisphosphonates, such as zoledronic acid (Zometa) and pamidronate (Aredia), block the cells that dissolve bone, called osteoclasts. For multiple myeloma, either pamidronate or zoledronic acid is given by IV every 3 to 4 weeks. Each treatment of pamidronate lasts at least 2 hours, and each treatment of zoledronic acid lasts at least 15 minutes. Patients with existing severe kidney problems usually receive lower doses of pamidronate given over a longer time (such as 4 to 6 hours instead of 2 hours). Zoledronic acid is generally not recommended for these patients.

  • Denosumab (Xgeva) is an osteoclast-targeted therapy called a RANK ligand inhibitor. It is approved to treat multiple myeloma and may be a better option for people with severe kidney problems. Denosumab is considerably more expensive than bisphosphonates. It has been shown to have similar effectiveness to bisphosphonates.

Treatment with a bone-modifying drug is recommended for up to 2 years. At 2 years, treatment may be stopped if it is working. If the myeloma comes back and new bone problems develop, treatment with a bone-modifying drug is usually started again. Talk with your doctor for more information about stopping and restarting treatment with these drugs.

Side effects of bisphosphonates may include flu-like symptoms, anemia, and joint and muscle pain, and kidney problems. If you are taking pamidronate or zoledronic acid, you should have a blood test to check how well the kidneys are working before each time you receive the drug. Side effects of denosumab may include diarrhea, nausea, anemia, and back pain.

Osteonecrosis of the jaw is an uncommon but potentially serious side effect of both types of bone-modifying drugs. The symptoms may include pain, swelling, and infection of the jaw; loose teeth; and exposed bone. Before treatment, patients should receive a thorough dental examination, and any tooth or mouth infections should be treated. While receiving treatment with a bone modifying drug, patients should avoid having any invasive dental work done, such as dental surgery. Take care of your teeth, gums, and tongue with regular brushing and flossing. Learn more about dental and oral health during cancer treatment.

Bone-modifying drugs are not always recommended for people with the following conditions:

  • Solitary plasmacytoma (1 bone tumor)

  • Smoldering (indolent) myeloma

  • Conditions of abnormal plasma cells that are not myeloma but may eventually become myeloma, such as MGUS

This information on bone modifying drugs is based on ASCO recommendations for bisphosphonate treatment for multiple myeloma. (Please note that this link takes you to another ASCO website.)

Bone marrow transplantation/stem cell transplantation

A bone marrow transplant is a medical procedure in which bone marrow that contains cancer is replaced by highly specialized cells, called hematopoietic stem cells, that develop into healthy red blood cells, white blood cells, and platelets in the bone marrow. Hematopoietic stem cells are blood-forming cells found both in the bloodstream and in the bone marrow. This procedure is also called a stem cell transplant. This is because it is the stem cells in the blood that are typically being transplanted, not the actual bone marrow tissue.

Before recommending transplantation, doctors will talk with the patient about the risks of this treatment. They will also consider several other factors, such as the type of cancer, results of any previous treatment, and the patient’s age and general health.

There are 2 types of stem cell transplantation depending on the source of the replacement blood stem cells: allogeneic (ALLO) and autologous (AUTO). ALLO uses donated stem cells, while AUTO uses the patient’s own stem cells. For multiple myeloma, AUTO is more commonly used. ALLO is being studied in clinical trials. In both types, the goal is to destroy all of the cancer cells in the marrow, blood, and other parts of the body using high doses of chemotherapy (usually melphalan) and then allow replacement blood stem cells to create healthy bone marrow and better immunity.

Learn more about the basics of bone marrow and stem cell transplantation.

Radiation therapy

Radiation therapy is the use of high-energy x-rays or other particles to destroy cancer cells. A doctor who specializes in giving radiation therapy to treat cancer is called a radiation oncologist. The most common type of radiation treatment is called external-beam radiation therapy, which is radiation given from a machine outside the body. A radiation therapy regimen (schedule) usually consists of a specific number of treatments given over a set period of time.

Doctors may recommend radiation therapy for patients with bone pain when chemotherapy is not effective or in order to control pain. However, using radiation therapy is not an easy decision. In many instances, pain (especially back pain) is due to structural damage to the bone. Radiation therapy may not help this type of pain and may affect the bone marrow's response to future treatment.

Side effects of radiation therapy may include fatigue, mild skin reactions, upset stomach, and loose bowel movements. Most side effects go away soon after treatment is finished. Learn more about the basics of radiation therapy.

Surgery

Surgery is not usually a disease-directed treatment option for multiple myeloma, but it may be used to relieve symptoms (see below). Surgery is used to treat bone disease, especially if there are fractures, and recent plasmacytomas, especially if they occur outside the bone.

Physical, emotional, and social effects of cancer

Cancer and its treatment cause physical symptoms and side effects, as well as emotional, social, and financial effects. Managing all of these effects is called palliative care or supportive care. It is an important part of your care that is included along with treatments intended to slow, stop, or eliminate the cancer.

Palliative care focuses on improving how you feel during treatment by managing symptoms and supporting patients and their families with other, non-medical needs. Any person, regardless of age or type and stage of cancer, may receive this type of care. It often works best when it is started right after a cancer diagnosis. People who receive palliative care along with treatment for the cancer often have less severe symptoms, better quality of life, and report they are more satisfied with treatment.

Palliative treatments vary widely and often include medication, nutritional changes, relaxation techniques, emotional and spiritual support, and other therapies. You may also receive palliative treatments similar to those meant to get rid of the cancer, such as chemotherapy, surgery, or radiation therapy.

Before treatment begins, talk with your doctor about the goals of each treatment in the treatment plan. You should also talk about the possible side effects of the specific treatment plan and palliative care options.

During treatment, your health care team may ask you to answer questions about your symptoms and side effects and to describe each problem. Be sure to tell the health care team if you are experiencing a problem. This helps the health care team treat any symptoms and side effects as quickly as possible. It can also help prevent more serious problems in the future.

Learn more about the importance of tracking side effects in another part of this guide. Learn more about palliative care in a separate section of this website.

Refractory myeloma

The disease is called relapsed and refractory myeloma if the cancer no longer responds to the most recent treatment. If this happens, it is a good idea to talk with doctors who have experience in treating refractory myeloma. Doctors can have different opinions about the best standard treatment plan. Also, clinical trials might be an important option.

Sometimes drugs that have gone through advanced phases of clinical trial and are awaiting FDA approval are made more readily available to patients with refractory myeloma through FDA’s Expanded Access Clinical Trial Program. For example, daratumumab was first approved in 2015 to be used alone to treat relapsed and refractory myeloma after other treatments had failed. In November 2016, the FDA approved the use of daratumumab in combination with lenalidomide and dexamethasone or with bortezomib and dexamethasone to treat people who have already received at least 1 previous treatment. Since then, daratumumab has received 5 more approvals from the FDA and is now approved in combination with bortezomib, thalidomide, and dexamethasone to treat newly diagnosed patients with multiple myeloma who may also receive an AUTO stem cell transplant. You may want to talk to your doctor about availability of treatments being studied in clinical trials.

Learn more about getting a second opinion before starting treatment, so you are comfortable with your chosen treatment plan.

For people with refractory myeloma, palliative care may also be important to help relieve symptoms and side effects.

For most people, a diagnosis of relapsed or refractory myeloma is very stressful and difficult. You and your family are encouraged to talk about how you feel with your doctors, nurses, social workers, or other members of the health care team. It may also be helpful to talk with other patients, such as through a support group or other peer support program.

Remission and the chance of recurrence

A remission is when cancer cannot be detected in the body and there are no symptoms. A remission may be temporary or permanent. This uncertainty causes many people to worry that the cancer will come back. It is important to talk with your doctor about the possibility of the cancer returning, which is almost certain with myeloma, despite recent advances in therapy. Understanding your risk of recurrence and the treatment options may help you feel more prepared if the cancer does return. Learn more about coping with the fear of recurrence.

If the cancer returns after the original treatment, it is called recurrent myeloma or relapsed myeloma. When this occurs, a cycle of testing will begin again to learn as much as possible about the recurrence. After testing is done, you and your doctor will talk about the treatment options. Often the treatment plan will include the treatments described above such as targeted therapy and chemotherapy, but they may be used in a different combination or given at a different pace. Recent advances in targeted, newer therapy mean that the chances of effective treatment for relapsed disease are increasing.

Your doctor may also suggest clinical trials that are studying new ways to treat recurrent or relapsed myeloma. There are multiple drugs currently being researched in the late stages of clinical trials that have shown promise as treatments for recurrent or relapsed myeloma. See the Latest Research section for more information. Whichever treatment plan you choose, palliative care will also be important for relieving symptoms and side effects.

People with relapsed myeloma often experience emotions such as disbelief or fear. You are encouraged to talk with the health care team about these feelings and ask about support services to help you cope. Learn more about dealing with cancer recurrence.

If treatment does not work

Recovery from and a cure for myeloma are unlikely. The disease is still considered incurable despite recent progress. If the cancer cannot be controlled even with the newer treatments available, the disease may be called advanced or terminal.

This diagnosis is stressful, and advanced cancer is difficult to discuss for many people. But it is important to have open and honest conversations with your health care team to express your feelings, preferences, and concerns. The health care team has special skills, experience, and knowledge to support patients and their families and is there to help. Making sure a person is physically comfortable, free from pain, and emotionally supported is extremely important.

People who have advanced cancer and who are expected to live less than 6 months may want to consider hospice care. Hospice care is designed to provide the best possible quality of life for people who are near the end of life. You and your family are encouraged to think about where you would be most comfortable: at home, in the hospital, or in a hospice environment. Nursing care and special equipment can make staying at home a workable alternative for many families. Learn more about advanced cancer care planning.

After the death of a loved one, many people need support to help them cope with the loss. Learn more about grief and loss.

The next section in this guide is About Clinical Trials. It offers more information about research studies that are focused on finding better ways to care for people with cancer. Use the menu to choose another section to read in this guide.