Drug Therapy for Multiple Myeloma

Drugs are the main type of treatment for nearly everyone with multiple myeloma.

Although a single drug might sometimes be used to treat multiple myeloma, most often 2 to 4 different kinds of drugs are combined, because the cancer tends to respond better. The choice of which drugs to use depends on many factors, including:

• The traits of the myeloma (including if it's considered high risk or standard risk)
• A person's age, kidney function, and overall health
• If the person might get a stem cell transplant as part of their treatment

For more on some of the combinations of drugs that might be used, see Treatment Options for Multiple Myeloma and Other Plasma Cell Disorders.

Chemotherapy

Chemotherapy (chemo) is the use of certain kinds of drugs that destroy or control the growth of cancer cells. These drugs can be taken by mouth or given in a vein or a muscle. They enter the bloodstream and reach almost all areas of the body.

At one time, chemo was often part of the main treatment for multiple myeloma. As newer types of drugs have become available in recent years, chemo has become less important in treating myeloma, although it still might be used in some situations.

Chemo drugs that can be used to treat multiple myeloma include:

• Cyclophosphamide
• Etoposide (VP-16)
• Doxorubicin (Adriamycin)
• Liposomal doxorubicin (Doxil)
• Melphalan
• Bendamustine

Often one of these drugs is combined with other types of drugs like corticosteroids and immunomodulating drugs (see below). If a stem cell transplant is planned as part of a person's treatment, most doctors avoid using certain chemo drugs, like melphalan, that can damage bone marrow.

Chemo side effects

Chemo drugs kill cancer cells but also can damage normal cells, which can lead to side effects. These side effects depend on the type and dose of drugs given and how long they are taken. Common side effects of chemo include:

• Hair loss
• Mouth sores
• Loss of appetite
• Nausea and vomiting
• Diarrhea or constipation

Chemotherapy often leads to low blood counts, which can cause:

• An increased risk of serious infection (from having too few white blood cells)
• Easy bruising or bleeding (from having too few blood platelets )
• Feeling tired or short of breath (from having too few red blood cells)

Most side effects go away after treatment is finished.

If you have side effects, your cancer care team can suggest steps to ease them. For example, drugs can be given along with the chemo to prevent or reduce nausea and vomiting.

Along with these short-term side effects, some chemo drugs can cause long-term damage to certain organs such as the heart or kidneys. The possible risks of these drugs are carefully balanced against their benefits, and the function of these organs is carefully monitored during treatment.

For more information about chemo and its side effects, see Chemotherapy.

Corticosteroids (steroids)

Corticosteroids, such as dexamethasone and prednisone, are an important part of the treatment of multiple myeloma. They can be used alone or combined with other drugs as a part of treatment. Corticosteroids can also be used to help reduce the nausea and vomiting that chemo might cause.

Side effects of corticosteroids

Common side effects of these drugs can include:

• High blood sugar
• Increased appetite and weight gain
• Problems sleeping
• Changes in mood, such as becoming irritable or “hyper”

When used for a long time, corticosteroids can also suppress the immune system, which increases the risk of serious infections. Steroids can also weaken bones.

Most of these side effects go away over time after the drug is stopped.

Immunomodulatory drugs (IMiDs)

Immunomodulatory drugs (IMiDs) affect the immune system, although exactly how they do this isn’t entirely clear. These drugs are often helpful in treating multiple myeloma.

These drugs are taken daily as pills, with breaks from treatment on certain days each month.

The IMiDs might cause severe birth defects when taken during pregnancy, so they can only be obtained through a special program run by the drug company that makes them.

Because these drugs can increase the risk of serious blood clots, they are often given along with aspirin or a blood thinner.

Thalidomide (Thalomid)

Thalidomide was first IMiD used to treat multiple myeloma.

Side effects of thalidomide can include drowsiness, fatigue, severe constipation, and painful nerve damage (neuropathy). The neuropathy can be severe, and it might not go away after the drug is stopped. There is also an increased risk of serious blood clots that start in the leg and can travel to the lungs.

Lenalidomide (Revlimid)

Lenalidomide is similar to thalidomide, although it tends to have less severe side effects. This is often the first IMiD used in treating multiple myeloma.

The most common side effects of lenalidomide are thrombocytopenia (low blood platelet counts) and low white blood cell counts. It can also cause painful nerve damage. The risk of blood clots is not as high as that seen with thalidomide, but it is still increased.

Pomalidomide (Pomalyst)

Pomalidomide can also be used to treat multiple myeloma, most often after other treatments have been tried.

Some common side effects of pomalidomide include low red blood cell counts (anemia) and low white blood cell counts. The risk of nerve damage is not as severe as it is with the other IMiDs, but it’s also linked to an increased risk of blood clots.

Proteasome inhibitors

Proteasome inhibitors work by stopping enzyme complexes (proteasomes) in cells from breaking down proteins important for controlling cell division. They appear to affect tumor cells more than normal cells.

Bortezomib (Velcade)

Bortezomib was the first of this type of drug to be approved, and it’s often used to treat multiple myeloma. It may be especially helpful in treating people with kidney problems.

It’s injected into a vein (IV) or under the skin, once or twice a week.

Common side effects of bortezomib include nausea and vomiting, tiredness, diarrhea, constipation, fever, loss of appetite, and lowered blood counts. The platelet count (which can cause easier bruising and bleeding) and the white blood cell count (which can increase the risk of serious infection) are most often affected. Bortezomib can also cause nerve damage (peripheral neuropathy) that can lead to problems with numbness, tingling, or even pain in the hands and feet. The risk of nerve damage is less when the drug is given under the skin. Some people develop shingles (herpes zoster) while taking this drug. To help prevent this, your doctor may have you take an anti-viral medicine (like acyclovir) while you take bortezomib.

Carfilzomib (Kyprolis)

Carfilzomib is a newer proteasome inhibitor that can be used to treat multiple myeloma, typically after other drugs have been tried. It’s given as an injection into a vein (IV), often in a 4-week cycle. To help prevent problems like allergic reactions during the infusion, the steroid drug dexamethasone is often given before each dose in the first cycle.

Common side effects of carfilzomib include tiredness, nausea and vomiting, diarrhea, shortness of breath, fever, and low blood counts, including the platelet count (which can cause easier bruising and bleeding) and the red blood cell count (which can lead to tiredness and shortness of breath). People on this drug can also have more serious problems, such as pneumonia, heart problems, and kidney or liver failure.

Ixazomib (Ninlaro)

Ixazomib is a proteasome inhibitor that is a capsule taken by mouth, typically once a week for 3 weeks, followed by a week off. This drug is usually given after other drugs have been tried.

Common side effects of ixazomib include nausea and vomiting, diarrhea, constipation, swelling in the hands or feet, back pain, and a lowered blood platelet count (which can cause easier bruising and bleeding). This drug can also cause nerve damage (peripheral neuropathy) that can lead to problems with numbness, tingling, or even pain in the hands and feet.

Monoclonal antibodies

Antibodies are proteins made by the body’s immune system to help fight infections. Man-made versions (monoclonal antibodies) can be designed to attack a specific target, such as proteins on the surface of myeloma cells.

Antibodies against CD38

The CD38 protein is found on myeloma cells. Monoclonal antibodies that target this protein seem to work both by killing the cancer cells directly and by helping the immune system attack them.

Daratumumab (Darzalex and Darzalex Faspro)

Daratumumab is a monoclonal antibody that attaches to the CD38 protein. This drug is used mainly in combination with other types of drugs, although it can also be used by itself in people who have already had several other treatments for myeloma.

This drug is often given as an infusion into a vein (IV). A newer form of the drug, known as daratumumab and hyaluronidase (Darzalex Faspro), can be given as a subcutaneous (under the skin) injection, typically in the belly area over a few minutes.

Either form of this drug can cause a reaction in some people while it is being given or within several hours afterward, which can sometimes be severe. Symptoms can include coughing, wheezing, trouble breathing, tightness in the throat, a runny or stuffy nose, feeling dizzy or lightheaded, headache, rash, and nausea.

Other side effects can include fatigue, nausea, back pain, fever, and cough. This drug can also lower blood cell counts, which can increase the risk of infections and bleeding or bruising. Darzalex Faspro can also cause reactions at the injection site, such as swelling, itching, and redness.

Isatuximab (Sarclisa)

Isatuximab is another monoclonal antibody that attaches to the CD38 protein on myeloma cells. This drug is used along with other types of myeloma drugs, either as part of the first treatment or after other treatments have been tried. It’s given as an infusion into a vein (IV).

This drug can cause a reaction in some people while it is being given or within a few hours afterward, which can sometimes be severe. Symptoms can include coughing, wheezing, trouble breathing, tightness in the throat, chills, feeling dizzy or lightheaded, headache, rash, and nausea.

The most common side effects of this drug include respiratory infections (such as colds or pneumonia) and diarrhea. This drug can also lower blood cell counts: 

• Having too few white blood cells can increase your risk for infections.
• Having too few red blood cells (anemia) can make you feel tired and weak.
• Having too few blood platelets can increase your risk of bleeding and bruising easily. 

This drug might also increase your risk of developing a second cancer.

Antibodies against SLAMF7

SLAMF7 is another protein found on myeloma cells. Antibodies that target this protein can help the immune system attack the cancer cells.

Elotuzumab (Empliciti)

Elotuzumab is a monoclonal antibody that attaches to the SLAMF7 protein. This drug is used mainly in people who have already had other treatments for their myeloma. It’s given as an infusion into a vein (IV).

This drug can cause a reaction in some people while it is being given or within several hours afterward, which can sometimes be severe. Symptoms can include fever, chills, feeling dizzy or lightheaded, rash, wheezing, trouble breathing, tightness in the throat, or a runny or stuffy nose.

Other common side effects with this drug include fatigue, fever, loss of appetite, diarrhea, constipation, cough, nerve damage resulting in weakness or numbness in the hands and feet (peripheral neuropathy), upper respiratory tract infections, and pneumonia.

Bispecific T cell engagers (BiTEs)

Some newer man-made antibodies are designed to attach to two different targets. These are known as bispecific antibodies.

An example are bispecific T-cell engagers (BiTEs). Once in the body, one part of these antibodies attaches to the CD3 protein on immune cells called T cells. Another part attaches to a specific protein on myeloma cells. This brings the two cells together, which helps the immune system attack the myeloma cells.

These medicines can be an option to treat multiple myeloma, typically after several other types of drugs have been tried.

Teclistamab (Tecvayli)

Teclistamab attaches to the BCMA protein on myeloma cells. This drug is given as an injection under the skin (subcutaneously), typically once every few days for the first week, then once a week. After several months, it can also be given once every 2 weeks.

Elrenatamab (Elrexfio)

Elrenatamab also attaches to the BCMA protein on myeloma cells. This drug is given as an injection under the skin (subcutaneously), typically once every few days for the first week, then once a week for several months, and then once every 2 weeks.

Talquetamab (Talvey)

Talquetamab attaches to the GPRC5D protein on myeloma cells (and some other cells). This drug is given as an injection under the skin (subcutaneously), typically once every few days for the first week, then either once a week or once every other week.

Side effects of BiTEs

Because these medicines can cause serious side effects when you first get them (see below), you will be started on a low dose, and you might be given other medicines to help lower the risk of side effects. You might need to stay in the hospital for a day or two after the first few doses.

Common side effects of these medicines include:

• Fever
• Feeling very tired
• Headache
• Nausea 
• Diarrhea
• Muscle and joint pain 
• Respiratory infections (including pneumonia)
• Low blood cell counts
• Skin rash
• Liver problems

These drugs can also cause more serious side effects, including:

Cytokine release syndrome (CRS): This is a serious side effect in which T cells in the body release chemicals (cytokines) that ramp up the immune system. This happens most often within the first day after treatment, and it can sometimes be life-threatening. Symptoms can include high fever and chills, feeling dizzy or lightheaded, trouble breathing, low blood pressure, headache, and a very fast heartbeat.

Nervous system problems: These drugs might affect the nervous system, which could lead to symptoms such as headaches, numbness or tingling in the hands or feet, feeling dizzy or confused, trouble speaking or understanding things, memory loss, abnormal sleep patterns, tremors, or seizures.

Your health care team will watch you closely for possible signs of CRS and nervous system problems, especially during and after the first few treatments. Be sure to contact your health care team right away if you have any of the symptoms above. 

These drugs might also cause other symptoms. Ask your health care team what you should look out for.

Nuclear export inhibitor

The nucleus of a cell holds most of the cell’s genetic material (DNA) needed to make the proteins the cell uses to function and stay alive. A protein called XPO1 helps carry other proteins from the nucleus to other parts of the cell.

Selinexor (Xpovio)

Selinexor is a drug known as a nuclear export inhibitor. It works by blocking the XPO1 protein. When the myeloma cell cannot transport proteins from its nucleus, the cell dies.

This drug can be used, along with the steroid dexamethasone:

• For people whose myeloma is no longer responding to other myeloma drugs, OR
• Along with bortezomib for people whose myeloma has grown on at least one other drug therapy

This drug is a pill that can be taken on the first and third day of each week or weekly.

Common side effects of selinexor include low platelet counts, low white blood cell counts, diarrhea, nausea, vomiting, not feeling hungry, weight loss, low blood sodium levels, and infections like bronchitis or pneumonia.

Bisphosphonates and other drugs for bone disease

Myeloma cells can weaken and even break bones. Drugs that affect bone cells can help bones stay strong by slowing down this process. They can also help reduce pain in the weakened bone(s). Sometimes, pain medicines such as NSAIDs or opioids will be given along with one of these medicines to help control or lessen pain from the bones.

The drugs used most often for treating bone problems in people with myeloma are the bisphosphonates pamidronate (Aredia) and zoledronic acid (Zometa) and the drug denosumab (Xgeva, other brand names). These drugs are given intravenously (IV or into a vein) or subcutaneously (under the skin). Most people are treated once a month at first, but they may be able to be treated less often later on if they are doing well.

Treatment with one of these drugs helps prevent further bone damage and events related to weakened bones such as fractures, hypercalcemia (high blood calcium levels), and spinal cord compression in people with multiple myeloma.

Side effects of bone medicines

Side effects of bisphosphonates can include flu-like symptoms and bone or joint pain. These drugs can also cause kidney problems, so people with poor kidney function might not be able to be treated with these medicines.

Common side effects of denosumab can include nausea, diarrhea, and feeling weak or tired. 

All of these medicines can have a rare but serious side effect called osteonecrosis of the jaw (ONJ), in which part of the jaw bone loses its blood supply and dies. This can lead to an open sore that doesn’t heal. It can also lead to tooth loss in that area. The jaw bone can also become infected.

Doctors aren’t sure why this happens or how best to prevent it, but having jaw surgery or having a tooth removed can sometimes trigger this problem, so it's important to avoid these procedures while you are taking any of these medicines. One way to avoid these procedures is to maintain good oral hygiene by flossing, brushing, making sure that dentures fit properly, and having regular dental checkups. Any tooth or gum infections should be treated right away. (Dental fillings, root canal procedures, and tooth crowns do not seem to lead to ONJ.) If ONJ does occur, the doctor will stop the bone medicine.

Your doctor might recommend that you have a dental checkup before starting treatment. That way, any dental problems can be taken care of before starting the drug. They might also recommend taking calcium and vitamin D supplements while taking the medicine to help your body build bone.