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Drug Therapies for Multiple Myeloma

There are a number of drug therapies beneficial to patients with multiple myeloma. Some drugs may be used alone, in combination with each other, or in combination with chemotherapy drugs. The drug or drugs used depends on each individual patient and conversations with their doctor about the cancer stage, patient age, kidney function, and overall health. Often times, a combination of 2 or 3 drugs will be given in order to get the best response. Learn more about the types of drugs used below. 

Corticosteroids (steroids)

Corticosteroids are often a standard part of treatment for multiple myeloma and help suppress inflammation. They can be used alone or combined with other drugs and are also used to help decrease chemotherapy side effects. Examples of corticosteroids are:

  • Dexamethasone, also called Decadron. Common side effects of corticosteroids include high blood sugar, proximal muscle weakness, insomnia, and mood changes.

Immunomodulating agents

Immunomodulating agents target the pathways that treat multiple myeloma. It’s not entirely clear how these agents affect the immune system, but they work to fight the cancerous cells in the body. Examples of immunomodulating agents are:

  • Thalidomide is a drug previously used in the 50s as a sleep aid and to treat motion sickness before being re-introduced as a powerful anti-myeloma agent. Side effects include drowsiness, rash, constipation, and thought slowing.
  • Lenalidomide (revlimid) is an analog of thalidomide. It has the potential side effects of venous thrombosis, a drop in blood counts, and rash.
  • Pomalidomide (Pomalyst) is a derivative of thalidomide. The most common side effects include tiredness, weakness, constipation, shortness of breath, diarrhea, fever, back pain, and nausea.

Proteasome inhibitors

Proteasome inhibitors stop enzyme complexes, or proteasomes, in the cells from breaking down proteins needed to control cell division. They affect tumor cells more than normal cells so may be prescribed to treat multiple myeloma. Examples include:

  • Bortezomib (Velcade) was the first of these types of drugs to be approved. This medication needs to be administered through an IV and is especially helpful for patients that have kidney problems. Potential side effects include nausea, vomiting, tiredness, diarrhea, constipation, fever, decreased appetite, and lowered blood counts. More seriously, bortezomib can also cause nerve damage, known as peripheral neuropathy.
  • Carfilzomib (Kyprolis) can be used to treat patients who have already been treated with other drugs that didn’t work. It’s given through an IV and common side effects include tiredness, nausea, vomiting, diarrhea, shortness of breath, fever, and low blood counts.
  • Ixazomib (Ninlaro) is an oral proteasome inhibitor typically 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.

Histone deacetylase inhibitors

Histone deacetylase inhibitors work to inhibit tumor cells in the body. They help uncoil the DNA and activate genes to stop or slow the growth of cancerous cells. These drugs include:

  • Panobinostat (Farydak) is taken orally and is usually given to patients that have already received two prior treatment regimens or have recurrent myeloma. The most common side effects include diarrhea, fatigue, nausea, decreased appetite, vomiting, fever, or swelling of the legs.

Monoclonal Antibodies

Antibodies are proteins made by the body to help fight infections. Monoclonal antibodies are man-made versions of these proteins that can be designed to attack a specific target, like myeloma cells. These include:

  • Daratumumab (Darzalex) is given through an IV and attaches to the CD38 protein found on myeloma cells. It is thought to kill the cancer cells directly and help the immune system fight them off. This drug is often used in combination with other drug types but can be used alone when patients have already received other treatments. Another form of the drug called hyaluronidase (Faspro), can be given as an under the skin injection. Symptoms for either form of the drug can include coughing, wheezing, trouble breathing, tightness in the throat, a runny or stuffy nose, feeling dizzy or lightheaded, headache, rash, and nausea.
  • Isatuximab (Sarclisa) is also given through an IV and attaches to the CD38 protein on myeloma cells. It is used along with other types of myeloma drugs, typically after at least 2 other treatments have been tried. Symptoms can include coughing, wheezing, trouble breathing, tightness in the throat, chills, feeling dizzy or lightheaded, headache, rash, and nausea.
  • Elotuzumab (Empliciti) attaches to the SLAMF7 protein, another protein found on myeloma cells, and attacks those cancer cells. It is used mainly in patients who have already had other treatments for their myeloma and is given through an IV. Symptoms include fever, chills, dizziness, rash, wheezing, tightness in the throat, or a runny or stuffy nose.

Antibody-drug conjugates

Antibody-drug conjugates are a monoclonal antibody linked to a chemotherapy drug. These are used to bring chemotherapy directly to the BCMA protein on myeloma cells. A common antibody-drug conjugate used includes:

  • Belantamab mafodotin-blmf (Blenrep) is given through an IV and can be used by itself to treat myeloma in people who have already had at least 4 other treatments for their disease (including proteasome inhibitors, immunomodulatory drugs, and a monoclonal antibody to CD38). Common side effects include feeling very tired, fever, nausea, and reactions when the drug is given.

Nuclear export inhibitors

The nucleus, or center of a cell contains most of the cell’s DNA that form proteins in that cell. One protein, XPO1, helps carry other proteins from the center to the rest of the cell. Nuclear export inhibitors work to block the XPO1 protein, so it stops carrying myeloma proteins and effectively kills that cell. Nuclear export inhibitors include:

  • Selinexor (Xpovio) is an oral medication given in combination with dexamethasone for people who have been treated and are no longer responding to at least 5 other myeloma drugs or along with bortezomib for myeloma that has grown while taking at least one other therapy. Side effects may include low platelet counts, low white blood cell counts, diarrhea, nausea, vomiting, not feeling hungry, weight loss, low blood sodium levels, and infections.

Chimeric antigen receptor (CAR) T-cell therapies

Chimeric antigen receptor (CAR) T-cell therapy is a novel form of immunotherapy that uses a patient’s own immune system to fight myeloma. This therapy applies to patients who received four or more previous lines of therapy, including a proteasome inhibitor, an immunomodulatory agent and an anti-CD38 monoclonal antibody.

  • Idecabtagene vicleucel (Abecma) is genetically engineered to let the CAR T cells find BCMA, a protein present at high amounts in multiple myeloma cells. Side effects include overactive immune responses, low blood cell counts, confusion, seizures, tremors, and delirium.
  • Ciltacabtagene autoleucel (Carvykti) is also a genetically engineered therapy designed to target BCMA protein on the surface of myeloma cells. Side effects include infections, nerve problems, or flu-like symptoms.

Investigational Agents

There are a number of drugs in development for the treatment of myeloma and other plasma cell disorders. The Weill Cornell Medicine Myeloma Center leads and participates in various clinical trials looking for new treatment options or combinations of treatments for our patients that have not yet been approved by the U.S. Food and Drug Administration (FDA). Patients may have the opportunity to participate in these studies after speaking to our physicians to discuss their treatment options and disease state. Clinical trials can be used as a front-line therapy for patients or if other treatments are not working as expected. Our physicians monitor all patients involved in research closely. Participation in clinical trials is completely voluntary and there is absolutely no obligation to enroll.

All treatment options will be discussed thoroughly between the patient and the physician to come to a therapy or combination of therapy that will benefit or be the most appropriate for that individual. Not all therapies will be appropriate for each patient, and some may benefit from different combinations than others.

Weill Cornell Medicine Myeloma Center 425 East 61st St
8th Floor
New York, NY 10065 Phone: (646) 962-6500 Fax: (212) 746-8961