Targeted therapy for multiple myeloma

Targeted therapy is usually used to treat multiple myeloma. It uses drugs to target specific molecules (such as proteins) on or inside cancer cells. 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.

You may have targeted therapy to:

• kill multiple myeloma cells
• lower the number of cancer cells in the body (called induction therapy) before a stem cell transplant
• destroy cells in the bone marrow as part of stem cell transplant conditioning
• make a stem cell transplant work better (called consolidation therapy)
• reduce the risk of a relapse (recurrence) and keep the cancer in remission after a stem cell transplant (called maintenance therapy)
• treat multiple myeloma that relapses or is no longer responding to treatment (refractory treatment)

Your healthcare team will consider your personal needs to plan the drugs, doses and schedules of targeted therapy. Targeted therapy drugs may be combined with chemotherapy drugs or supportive therapy drugs.

The following types of targeted therapy drugs are used to treat multiple myeloma.

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 may help stop the growth of cancer cells or destroy them.

Bortezomib (Velcade) is a proteasome inhibitor used to treat multiple myeloma. Bortezomib is usually given once a week as an injection under the skin (subcutaneous) or sometimes through a vein (intravenous). Bortezomib may be used alone or combined with the following drugs to treat multiple myeloma:

• VMP regimen – melphalan (Alkeran, L-PAM) and prednisone
• dexamethasone (Decadron, Dexasone)
• VTD regimen – thalidomide (Thalomid) and dexamethasone
• VRD regimen – lenalidomide (Revlimid) and dexamethasone
• CyBorD regimen – cyclophosphamide (Cytoxan, Procytox) and dexamethasone
• cyclophosphamide and prednisone
• liposomal doxorubicin (Myocet)
• doxorubicin (Adriamycin) and dexamethasone
• VTD-PACE regimen – dexamethasone, thalidomide, cisplatin (Platinol AQ), doxorubicin, cyclophosphamide (Cytoxan, Procytox) and etoposide (Vepesid, VP-16)

Carfilzomib (Kyprolis) is a proteasome inhibitor that is sometimes used to treat multiple myeloma that relapses or no longer responds to treatment. Carfilzomib is usually given several times per month as an injection into a vein (intravenous). Carlizomib is given in combination with lenalidomide and dexamethasone.

Ixazomib (Ninlaro) is a proteasome inhibitor that is sometimes used to treat multiple myeloma when other treatments aren’t working. It is given as a pill and taken by mouth. Ixazomib is used in combination with lenalidomide and dexamethasone.

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.

Thalidomide (Thalomid) is an immunomodulating drug and an anti-angiogenesis agent. Anti-angiogenesis agents prevent a tumour from developing new blood vessels.

Thalidomide is given as a pill and taken by mouth. It may be used alone or combined with the following drugs to treat multiple myeloma:

• MPT regimen – melphalan and prednisone
• dexamethasone
• VTD regimen – bortezomib and dexamethasone
• DT-PACE regimen – dexamethasone, cisplatin, doxorubicin, cyclophosphamide and etoposide
• VTD-PACE regimen – dexamethasone, cisplatin, doxorubicin, cyclophosphamide, etoposide and bortezomib 

Lenalidomide (Revlimid) is an immunomodulating drug similar to thalidomide. It is a stronger drug than thalidomide so side effects tend to be different and worse. Lenalidomide is most often used when myeloma relapses or no longer responds to treatment.

Lenalidomide is given as a pill and taken by mouth. It may be combined with the following drugs to treat multiple myeloma:

• dexamethasone
• VRD regimen – bortezomib and dexamethasone
• MPL regimen – melphalan and prednisone

Lenalidomide may also be combined with dexamethasone to treat myeloma when a stem cell transplant is not possible.

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

Monoclonal antibodies are versions of immune system proteins (which are called antibodies) that are made in the lab. Monoclonal antibodies block a target on the outside of a cancer cell.

Daratumumab (Darzalex) is a new monoclonal antibody that is sometimes used to treat multiple myeloma. It may be used along with lenalidomide and dexamethasone to treat people with newly diagnosed multiple myeloma who are unable to have a stem cell transplant. Daratumumab may also be used in combination with bortezomib and dexamethasone or lenalidomide and dexamethasone when other treatments aren't working.

Daratumumab may be used to treat multiple myeloma that relapses or no longer responds to other treatments. It is used in combination with pomalidomide and dexamethasone if you have received at least one other treatment, including lenalidomide and a proteasome inhibitor.

If you have relapsed after receiving one to three previous treatments, you may receive daratumumab in combination with carfilzomib and dexamethasaone.

Daratumumab is given as an injection into a vein (intravenous) every week for the first 8 weeks and then less often until the disease no longer responds to treatment.

Isatuximab (Sarclisa) is a monoclonal antibody that may be used to treat multiple myeloma that relapses or no longer responds to other treatments. It is used if you have received at least two other treatments, including lenalidomide and a proteasome inhibitor. Isatuximab is given along with pomalidomide and dexamethasone.

Elotuzumab (Empliciti) is a monoclonal antibody that may be used to treat multiple myeloma if one or more other treatments haven’t worked. Elotuzumab is given as an injection into a vein in combination with lenalidomide (Revlamid) and dexamethasone.

Side effects can happen with any type of treatment for multiple myeloma, but everyone’s experience is different. Some people have many side effects. Other people have few or none at all.

Targeted therapy doesn’t usually damage healthy cells, so it tends to cause fewer and less severe side effects than chemotherapy and radiation therapy. Chemotherapy and radiation therapy often damage healthy cells along with cancer cells.

If side effects develop with targeted therapy, they can happen any time during, immediately after or a few days or weeks after targeted therapy. Sometimes late side effects develop months or years after targeted therapy. Most side effects go away on their own or can be treated, but some side effects may last a long time or become permanent.

Side effects of targeted therapy will depend mainly on the type of drug or combination of drugs, the dose, how it’s given (by mouth or by vein) and your overall health. Some common side effects of targeted therapy drugs used for multiple myeloma are:

• drowsiness and fatigue
• constipation
• diarrhea
• nerve pain (called neuropathy), including peripheral neuropathy (pain, burning, numbness or feeling of pins and needles in the hands, arms, feet or legs)
• low white blood cell counts (called neutropenia), low red blood cell counts (called anemia) or low platelet counts (called thrombocytopenia)
• infection
• stuffy or runny nose, cough, chills and sore throat
• shortness of breath
• skin rash
• blood clots
• birth defects

Pregnant women or women planning to become pregnant should not take thalidomide, lenalidomide or pomalidomide because of the risk that they may cause severe birth defects.

Tell your healthcare team if you have these side effects or others you think might be from targeted therapy. The sooner you tell them of any problems, the sooner they can suggest ways to help you deal with them.

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

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