Drug Therapy for Multiple Myeloma

Chemotherapy

Chemotherapy (chemo) is the use of drugs to destroy or control 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.

Chemo drugs used to treat multiple myeloma include:

  • Melphalan
  • Vincristine (Oncovin)
  • Cyclophosphamide (Cytoxan)
  • Etoposide (VP-16)
  • Doxorubicin (Adriamycin)
  • Liposomal doxorubicin (Doxil)
  • Bendamustine (Treanda)

Often one of these drugs is combined with other types of drugs like corticosteroids and immuno-modulating agents (drugs that will change the patient’s immune response). If a stem cell transplant is planned, most doctors avoid using certain drugs, like melphalan, that can damage bone marrow.

Chemo side effects

Chemo drugs kill cancer cells but also can damage normal cells. They are given carefully to avoid or reduce the side effects of chemotherapy. These side effects depend on the type and dose of drugs given and the how long they are taken. Common side effects of chemotherapy include:

  • Hair loss
  • Mouth sores
  • Loss of appetite
  • Nausea and vomiting
  • Low blood counts

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

  • Infection: An increased risk of serious infection (from low white blood cell counts)
  • Easy bruising or bleeding (from low blood platelets )
  • Anemia: Feeling excessively tired or short of breath (low red blood cells)

Most side effects are temporary and 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.

In addition to these temporary side effects, some chemo drugs can permanently damage 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. If serious organ damage occurs, the drug that caused it is stopped and sometimes replaced with another.

For more information about chemotherapy 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 are also used to help decrease the nausea and vomiting that chemo might cause.

Common side effects of these drugs include

  • High blood sugar
  • Increased appetite and weight gain
  • Problems sleeping
  • Changes in mood (some people become irritable or “hyper”)

When used for a long time, corticosteroids also suppress the immune system. This 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.

Immunomodulating agents

The way immunomodulating agents affect the immune system isn’t entirely clear. Three immunomodulating agents are used to treat multiple myeloma. The first of these drugs to be developed, thalidomide, caused severe birth defects when taken during pregnancy. Because the other immunomodulating agents are related to thalidomide, there’s concern that they could also cause birth defects. That’s why all of these drugs 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) was first used decades ago as a sedative and as a treatment for morning sickness in pregnant women. When it was found to cause birth defects, it was taken off the market. Later, it became available again as a treatment for multiple myeloma. Side effects of thalidomide can include drowsiness, fatigue, severe constipation, and painful nerve damage (neuropathy). The neuropathy can be severe, and 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) is similar to thalidomide. It works well in treating multiple myeloma. The most common side effects of lenalidomide are thrombocytopenia (low platelets) 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.

In patients, where the myeloma is in remission after either a stem cell transplant or initial treatment, lenalidomide may be given for maintenance therapy to prolong the remission. 

Pomalidomide (Pomalyst) is also related to thalidomide and is used to treat multiple myeloma. Some common side effects 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 immunomodulating drugs, 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, but they are not without side effects.

Bortezomib (Velcade) 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 myeloma patients with kidney problems. It’s injected into a vein (IV) or under the skin, once or twice a week.

Common side effects of this drug include nausea and vomiting, tiredness, diarrhea, constipation, fever, decreased 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 patients 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.

In patients where the myeloma was put into remission after either a stem cell transplant or initial treatment, bortezomib may also be given for maintenance therapy to prolong the remission. 

Carfilzomib (Kyprolis) is a newer proteasome inhibitor that can be used to treat multiple myeloma in patients who have already been treated with other drugs that didn't work. It’s given as an injection into a vein (IV), often in a 4-week cycle. To 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 include tiredness, nausea and vomiting, diarrhea, shortness of breath, fever, and low blood counts. The blood counts most often affected are the platelet counts (which can cause easier bruising and bleeding) and the red blood cell count (which can lead to tiredness, shortness of breath, and being pale). People on this drug can also have more serious problems, such as pneumonia, heart problems, and kidney or liver failure.

Ixazomib (Ninlaro) 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 this drug 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.

Histone deacetylase (HDAC) inhibitors

HDAC inhibitors are a group of drugs that can affect which genes are active or turned on inside cells. They do this by interacting with proteins in chromosomes called histones.

Panobinostat (Farydak) is an HDAC inhibitor that can be used to treat patients who have already been treated with bortezomib and an immunomodulating agent. It is a capsule, typically taken 3 times a week for 2 weeks, followed by a week off. This cycle is then repeated.

Common side effects include diarrhea (which can be severe), feeling tired, nausea, vomiting, loss of appetite, swelling in the arms or legs, fever, and weakness. This drug can also affect blood cell counts and the blood levels of certain minerals (such as potassium, sodium, and calcium). Less common but still serious side effects can include bleeding inside the body, liver damage, and changes in heart rhythm, which can sometimes be life threatening.

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.

Daratumumab (Darzalex) is a monoclonal antibody that attaches to the CD38 protein, which is found on myeloma cells. This is thought to both kill the cancer cells directly and to help the immune system attack them also. This drug is used mainly in combination with other types of drugs, although it can also be used by itself in patients who have already had several 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 a few 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.

Elotuzumab (Empliciti) is a monoclonal antibody that attaches to the SLAMF7 protein, which is found on myeloma cells. This is thought to help the immune system attack the cancer cells. This drug is used mainly in patients 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.

Using these drugs together to treat multiple myeloma

Although a single drug may be used to treat multiple myeloma, it is preferable to use at least 2 or 3 different kinds of drugs in combination because the cancer responds better. For example:

  • Lenalidomide (or pomalidomide or thalidomide) and dexamethasone
  • Carfilzomib (or ixazomib or bortezomib), lenalidomide, and dexamethasone
  • Bortezomib (or carfilzomib), cyclophosphamide, and dexamethasone
  • Elotuzumab (or daratumumab), lenalidomide, and dexamethasone
  • Bortezomib, liposomal doxorubicin, and dexamethasone
  • Panobinostat, bortezomib, and dexamethasone
  • Elotuzumab, bortezomib, and dexamethasone
  • Melphalan and prednisone (MP), with or without thalidomide or bortezomib
  • Vincristine, doxorubicin (Adriamycin), and dexamethasone (called VAD)
  • Dexamethasone, cyclophosphamide, etoposide, and cisplatin (called DCEP)
  • Dexamethasone, thalidomide, cisplatin, doxorubicin, cyclophosphamide, and etoposide (called DT-PACE), with or without bortezomib

The choice and dose of drug therapy depend on many factors, including the stage of the cancer, the age and kidney function of the patient as well as how frail the patient may be. If a stem cell transplant is planned, most doctors avoid using certain drugs, like melphalan, that can damage the bone marrow.

Bisphosphonates for bone disease

Myeloma cells can weaken and even break bones. Drugs called bisphosphonates 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 narcotics will be given along with bisphosphonates to help control or lessen the pain. Bone pain can be a difficult symptom to treat during and after treatment for myeloma. 

The standard for treating bone problems in people with myeloma are pamidronate (Aredia), zoledronic acid (Zometa) and denosumab (Xgeva). These drugs are given intravenously (IV or into a vein). Most patients 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 a bisphosphonate helps prevent further bone damage in multiple myeloma patients.

These treatments can have a rare but serious side effect called osteonecrosis of the jaw (ONJ). Patients complain of pain and doctors find that part of the jaw bone has died. 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 trigger this problem. Avoid these procedures while you are taking a bisphosphonate. Many doctors recommend that patients have a dental checkup before starting treatment. That way, any dental problems can be taken care of before starting the drug. If ONJ does occur, the doctor will stop the bisphosphonate treatment.

One way to avoid these dental 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.

The American Cancer Society medical and editorial content team
Our team is made up of doctors and master's-prepared nurses with deep knowledge of cancer care as well as journalists, editors, and translators with extensive experience in medical writing.

Boussi L and Niesvizky R. Advances in immunotherapy in multiple myeloma. Curr Opin Oncol 2017, 29:460–466.

Dhodapkar MV et al. Hematologic Malignancies: Plasma Cell Disorders. 2017 ASCO EDUCATIONAL BOOK.

Dingli D et al. Therapy for Relapsed Multiple Myeloma: Guidelines From the Mayo Stratification for Myeloma and Risk-Adapted Therapy. Mayo Clin Proc. 2017 April ; 92(4): 578–598.

Jung SH, et al. Immunotherapy for the treatment of multiple myeloma. Critical Reviews in Oncology/Hematology. 2017; 111:87-93.

Leleu X, Attal M, Arnulf B, et al. Pomalidomide plus low dose dexamethasone is active and well tolerated in bortezomib and lenalidomide refractory multiple myeloma: IFM 2009-02. Blood. 2013;121(11):1968-1975. Epub 2013 Jan 14.

Munshi NC, Anderson KC. Ch. 112 Plasma cell neoplasms. In: DeVita VT, Hellman S, Rosenberg SA, eds. Cancer: Principles and Practice of Oncology. 10th edition. Philadelphia, PA: Lippincott Williams & Wilkins; 2015.

National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines in Oncology. Multiple myeloma. V.3.2018. Accessed at www.nccn.org on Dec. 7, 2017.

Palumbo A, Anderson K. Multiple myeloma. N Engl J Med. 2011;364(11):1046-1060.

Rajkumar SV. Treatment of Multiple Myeloma. Nat Rev Clin Oncol. 2011; 8(8): 479–491.

Rajkumar SV, Dispenzieri A. Multiple myeloma and related disorders. In: Niederhuber JE, Armitage JO, Doroshow JH, Kastan MB, Tepper JE. Abeloff’s Clinical Oncology. 5th edition. Philadelphia, PA. Elsevier: 2014:1991-2017.

Richardson PG, Schlossman RL, Alsina M, et al. PANORAMA 2: panobinostat in combination with bortezomib and dexamethasone in patients with relapsed and bortezomib-refractory myeloma. Blood. 2013;122(14):2331-2337. Epub 2013 Aug 15.

San Miguel J, Weisel K, Moreau P, et al. Pomalidomide plus low-dose dexamethasone versus high-dose dexamethasone alone for patients with relapsed and refractory multiple myeloma (MM-003): a randomised, open-label, phase 3 trial. Lancet Oncol. 2013;14(11):1055-1066. Epub 2013 Sep 3.

 

Last Medical Review: February 28, 2018 Last Revised: May 9, 2018

American Cancer Society medical information is copyrighted material. For reprint requests, please see our Content Usage Policy.