Targeted therapy for multiple myeloma

Targeted therapy uses drugs to target specific molecules (such as proteins) on cancer cells or inside them. These molecules help send signals that tell cells to grow or divide. By targeting these molecules, the drugs stop the growth and spread of cancer cells and limit harm to normal cells. Targeted therapy may also be called molecular targeted therapy.

Most people with multiple myeloma have targeted therapy. If you have targeted therapy, your healthcare team will use what they know about the cancer and about your health to plan the drugs, doses and schedules. Targeted therapy drug may be combined with chemotherapy drugs or supportive therapy drugs.

You may have targeted therapy to:

• destroy multiple myeloma cells
• lower the number of cancer cells in the body before a stem cell transplant (called induction therapy)
• lower the number of cancer cells in the body if you can't have a stem cell transplant
• help bring about a better response to treatment after a stem cell transplant (called consolidation therapy)
• keep the cancer in remission after a stem cell transplant (called maintenance therapy)
• keep the cancer in remission after induction therapy if you can't have a stem cell transplant
• treat multiple myeloma that has come back after it was treated (called relapsed multiple myeloma) or is no longer responding to treatment (called refractory multiple myeloma)

Different types of targeted therapy are used for multiple myeloma. These include:

• proteasome inhibitors
• immunomodulating drugs
• monoclonal antibodies
• selective inhibitors of nuclear export (SINE) drugs

Targeted therapy drugs used for multiple myeloma may not be covered by all provincial and territorial health plans.

Side effects of targeted therapy will depend mainly on the type of drug or combination of drugs, the dose, how it's given and your overall health. Tell your healthcare team if you have side effects that you think are from targeted therapy. The sooner you tell them of any problems, the sooner they can suggest ways to help you deal with them.

Proteasome inhibitors are a type of targeted therapy that block proteasomes. Proteasomes are a group of special proteins called enzymes that cancer cells need to grow. Interfering with how proteasomes work helps stop the growth of cancer cells or destroy them.

Bortezomib (Velcade) is a proteasome inhibitor used to treat active multiple myeloma. Bortezomib is usually given through a needle into, and just under, the skin (subcutaneously) or sometimes through a needle into a vein (intravenously). Bortezomib is a very common drug used in many drug combinations. It can be given alone or in combination with other targeted therapy drugs, chemotherapy drugs and supportive therapy drugs.

The most common drug combinations using bortezomib are:

• RVd – lenalidomide (Revlimid), bortezomib and low-dose dexamethasone
• CyBorD – cyclophosphamide, bortezomib and dexamethasone
• lenalidomide and bortezomib

Other combinations using bortezomib can also be used to treat multiple myeloma.

Carfilzomib (Kyprolis) is a proteasome inhibitor that is sometimes used to treat multiple myeloma that has come back after treatment (called relapsed multiple myeloma) or no longer responds to treatment (called refractory multiple myeloma). Carfilzomib is usually given through a needle into a vein.

Drug combinations using carfilzomib include:

• Kd – carfilzomib and low-dose dexamethasone
• KRd – carfilzomib, lenalidomide (Revlimid) and low-dose dexamethasone
• DKd – daratumumab (Darzalex), carfilzomib and low-dose dexamethasone
• Isa-Kd – isatuximab (Sarclisa), carfilzomib and low-dose dexamethasone
• KCd – carfilzomib, cyclophosphamide and low-dose dexamethasone

Ixazomib (Ninlaro) is a proteasome inhibitor that is sometimes used to treat relapsed or refractory multiple myeloma. It is given as a pill and taken by mouth. Ixazomib is used in combination with lenalidomide and dexamethasone.

Bortezomib, carfilzomib and ixazomib may cause these side effects:

• low platelet count
• infection
• reactivating a shingles infection
• nausea and vomiting
• diarrhea
• constipation
• peripheral nerve damage
• swelling (called edema)
• fatigue
• skin problems, such as rash and itching
• heart problems
• high blood pressure
• kidney problems

Immunomodulating drugs boost the immune system so they are also a type of immunotherapy. These drugs work by interfering with the growth and division of myeloma cells.

Lenalidomide (Revlimid) is an immunomodulating drug and an anti-angiogenesis agent. Anti-angiogenesis agents prevent a tumour from developing blood vessels. Lenalidomide is a common drug used to treat active multiple myeloma. Lenalidomide is given as a pill and taken by mouth. It may be given alone or in combination with other targeted therapy or supportive therapy drugs.

The most common drug combinations using lenalidomide are:

• RVd – lenalidomide, bortezomib (Velcade) and low-dose dexamethasone
• DRd – daratumumab (Darzalex), lenalidomide and low-dose dexamethasone
• lenadiomide and bortezomib

Other combinations using lenalidomide can also be used to treat multiple myeloma.

Thalidomide (Thalomid) is an immunomodulating drug that is similar to lenalidomide. Thalidomide can be used to treat multiple myeloma when you can have a stem cell transplant (called transplant eligible multiple myeloma). It is given as a pill and taken by mouth. Thalidomide may be combined with other targeted therapy, chemotherapy drugs or supportive therapy drugs.

Drug combinations using thalidomide include:

• VTd – bortezomib, thalidomide and low-dose dexamethasone
• D-VTd – daratumumab, bortezomib, thalidomide and low-dose dexamethasone
• VTd-PACE – bortezomib, thalidomide, low-dose dexamethasone, cisplatin, doxorubicin, cyclophosphamide and etoposide

Pomalidomide (Pomalyst) is another immunomodulating drug similar to lenalidomide and thalidomide. It may be combined with dexamethasone and bortezomib if treatment with lenalidomide and bortezomib has not worked. Pomalidomide is given as a pill and taken by mouth.

Lenalidomide, thalidomide and pomalidomide increase the risk of blood clots in the lungs and the heart, as well as deep vein thrombosis. If your treatment includes these drugs, you will be given drugs that help prevent blood clots, such as acetylsalicylic acid (ASA, Aspirin), heparin or warfarin.

Lenalidomide, thalidomide and pomalidomide may cause these other side effects:

• low blood cell counts
• infection
• constipation
• diarrhea
• fatigue
• swelling
• muscle cramps
• nausea and vomiting
• thyroid problems
• headache
• dizziness
• bleeding
• skin problems, such as a rash
• peripheral nerve damage
• a second cancer

Monoclonal antibodies were designed in a lab to recognize and lock onto certain protein markers on the surface of some cancer cells.

Daratumumab (Darzalex) is a monoclonal antibody used to treat active multiple myeloma. It is usually given as an injection just under the skin (subcutaneously). Daratumumab can be used in various drug combinations. It is usually given in combination with other targeted therapy, chemotherapy drugs and supportive therapy drugs.

The most common drug combinations using daratumumab are:

• DRd – daratumumab, lenalidomide (Revlimid) and low-dose dexamethasone
• D-RVd – daratumumab, lenalidomide, bortezomib (Velcade) and low-dose dexamethasone
• DVd – daratumumab, bortezomib and low-dose dexamethasone

Other combinations using daratumumab can also be used to treat multiple myeloma.

Isatuximab (Sarclisa) is a monoclonal antibody that may be used to treat relapsed or refractory multiple myeloma. It is usually given through a needle into a vein.

Isatuximab is given along with pomalidomide (Pomalyst) and dexamethasone if you have received at least 2 other treatments, including lenalidomide and a proteasome inhibitor.

Isatuximab can also be combined with carfilzomib (Kyprolis) and dexamethasone if you have received at least one prior treatment.

Talquetamab (Talvey) is a monoclonal antibody that may be used to treat relapsed or refractory multiple myeloma if you have received at least 3 other treatments, including a proteasome inhibitor, an immunomodulating drug and another monoclonal antibody. It is given through a needle into a vein.

Daratumumab, isatuximab and talquetamab may cause these side effects:

• negative drug reactions, such as infusion or allergic (anaphylactic) reactions
• low blood cell counts
• infection
• reactivating a hepatitis B infection
• fatigue
• shortness of breath
• cough
• joint and muscle pain
• nausea and vomiting
• diarrhea

Selective inhibitors of nuclear export (SINE) are drugs that block exportin 1 (XPO1). XPO1 is a protein that involves moving RNA from the cell's nucleus to the cytoplasm during the cell cycle. Some multiple myeloma cells create too much XPO1 protein, which helps the cancer cells to grow and divide rapidly.

Selinexor (Xpovio) blocks the XPO1 protein to stop the cell cycle and causes the cancer cell to die. It may be used in combination with bortezomib and dexamethasone to treat relapsed or refractory multiple myeloma. Selinexor is given as a pill and taken by mouth.

Selinexor may cause these side effects:

• low blood cell counts
• nausea and vomiting
• diarrhea
• loss of appetite
• weight loss
• constipation
• fatigue
• infection
• cough
• shortness of breath
• eye problems, such as cataracts
• fever

Find out more about targeted therapy. To make the decisions that are right for you, ask your healthcare team questions about targeted therapy.

Details on specific drugs change regularly. Find out more about sources of drug information and where to get details on specific drugs.