What medicines besides chemotherapy are used to treat multiple myeloma?

In addition to chemotherapy (chemo), these medicines are used to treat multiple myeloma:

• Immunomodulatory medicines (IMiDs). These help stimulate the immune system to kill cancer cells. They also keep new blood vessels from forming and feeding myeloma cells.

• Targeted therapy medicines. These target certain genes, proteins, or the tissue environment that contributes to cancer growth and survival. This way, they kill cancer cells but may cause less damage to normal cells than chemo.

• Corticosteroids (steroids). These are used to kill myeloma cells and boost effectiveness of other myeloma medicines. They may also reduce side effects such as nausea and vomiting from other medicines.

• Bone-modifying medicines. These are almost always part of multiple myeloma treatment. They help keep the bones strong and reduce bone pain and the risk of fractures.

When are these medicines used for multiple myeloma?

A combination of medicines that work in different ways is the main treatment for multiple myeloma. The types of medicines you get will depend mainly on:

• How quickly the myeloma is likely to grow and cause problems

• Whether or not you might be able to have a stem cell transplant

• Gene and protein changes found on or in the myeloma cells

• How well your kidneys are working

• The goal of treatment

• Your age and overall health

• Concerns you have about side effects

• What treatments you’ve had in the past

• Your preferences

Several combinations of these medicines may be advised:

• As the first treatment for myeloma

• As part of a stem cell transplant

• As a later treatment if the first treatment stops working, or if the myeloma starts growing again after treatment

• As maintenance therapy after initial treatment to help keep the myeloma in remission

Many medicines and combinations of medicines can be used. If treatment stops working, another combination can be used.

How are these medicines given for multiple myeloma?

Before treatment starts, you’ll meet with a medical oncologist. This is a doctor who specializes in treating cancer with medicines. They will talk with you about your treatment options and tell you what you can expect.

The medicines used to treat multiple myeloma can be given in these ways:

• IV (intravenous) infusion. You’ll get the medicine right into your blood through a tube (catheter) that’s been put into a vein. It might drip in slowly over a few hours. Or you may get it over a few minutes.

• Shot (injection). The medicine is given as an injection under your skin into tissue.

• By mouth (oral). You swallow these medicines as pills or liquids.

Oral medicines can be taken at home.

Medicines given by IV or injection are most often given in an outpatient setting. This means you get them at a hospital, clinic, or healthcare provider's office. Then you go home after treatment. In rare cases, you may need to stay in the hospital during treatment.

Your treatment team will watch you for reactions during your treatments

Which medicines are used to treat multiple myeloma?

Immunomodulatory medicines (IMiDs)

The way immunomodulating medicines affect the immune system isn’t fully understood. There are 3 oral IMiDs used to treat multiple myeloma:

• Thalidomide

• Lenalidomide

• Pomalidomide

The first of these medicines to be developed was thalidomide. It causes severe birth defects when taken during pregnancy. Because the other immunomodulating medicines are related to thalidomide, it’s possible they might also cause birth defects. Because of this, you can only get these medicines through a special program run by the medicine company that makes them. These medicines also can increase your risk of blood clots. They may be given with a blood thinner or aspirin.

Targeted therapy medicines

There are many kinds of targeted therapy medicines used to treat multiple myeloma. They include:

• Proteasome inhibitors. These include bortezomib, carfilzomib, and ixazomib. These medicines target enzymes in cells (called proteasomes) to help control cell division.

• Monoclonal antibodies. These include daratumumab alone or with hyaluronidase-fihj, isatuximab-irfc, and elotuzumab. These medicines bind to proteins on the surface of myeloma cells. By doing this, they can kill the cells or help the immune system find and attack them.

• Nuclear export inhibitor. This oral medicine is called selinexor. It kills myeloma cells by keeping them from moving proteins they need to live and grow out of the cell nucleus.

• Bispecific T-cell engagers. These include teclistamab-cqyv, elrenatamab-bcmm, and talquetamab-tgvs. They kill the myeloma cells by attaching to 2 targets. One target is on the immune cells called T cells called CD3. The other target is on the myeloma cells (cancer). When the medicine joins the 2 targets together, the T cells can cause the cancer cells to die.

• CAR T-cell therapy. The 2 approved therapies are called idecabtagene vicleucel and ciltacabtagene autoleucel. This type of treatment is made from your own immune cells called T cells. The treatment helps your body's immune system attack the myeloma cells. CAR T-cell therapy is given at centers with experience in this type of treatment.

Corticosteroids (steroids)

Corticosteroids, such as dexamethasone and prednisone, are a key part of multiple myeloma treatment. They can be used alone. But they are often given along with other medicines. They can kill myeloma cells. They also help control side effects from the disease and from other medicines used to treat multiple myeloma. For instance, they can help reduce bone pain, reduce calcium in the blood, and ease nausea and vomiting.

Bone-modifying medicines

These medicines help make bones strong and reduce the risk of bone fractures (breaks). Two types can be used. The choice depends on how well your kidneys are working:

• Bisphosphonates. These block the cells that dissolve bone (called osteoclasts). The medicines that can be used are pamidronate and zoledronic acid. They can help keep myeloma from causing more bone damage and can reduce bone pain.

• Denosumab. This is a targeted therapy medicine that targets osteoclasts to protect bone. It might be a better option for people with severe kidney problems.

Combining different types of medicine

Most of the time, more than 1 medicine is used to treat multiple myeloma. Many different combinations can be used. For instance, some common combos used as the first treatment for myeloma when transplant is possible include:

• Bortezomib, lenalidomide, and dexamethasone

• Bortezomib, cyclophosphamide, and dexamethasone

• Bortezomib, thalidomide, dexamethasone

• Carfilzomib, lenalidomide, and dexamethasone

• Daratumumab, bortezomib, lenalidomide, and dexamethasone

• Isatuximab-irfc/, lenalidomide, bortezomib, and dexamethasone

Combos used as the first treatment for myeloma when transplant is not planned include:

• Bortezomib, lenalidomide, and dexamethasone

• Daratumumab, lenalidomide, and dexamethasone

• Daratumumab, bortezomib, melphalan, prednisone

• Carfizomib/lenalidomide/dexamethasone

• Lenalidomide and low-dose dexamethasone

• Bortezomib, cyclophosphamide, and dexamethasone

One of the bone-modifying medicines is also given in most cases.

What are common side effects of these medicines?

All medicines used to treat multiple myeloma can cause side effects. Side effects can vary a lot based on the medicines and the combination of medicines used. Most side effects are short-term and get better over time after treatment ends. But some can be long-lasting.

Ask your healthcare provider for details about the side effects of the medicines you're getting and what can be done to help prevent and manage them.

Side effects of immunomodulating medicine

Thalidomide common side effects can include:

• Drowsiness and severe tiredness (fatigue)

• Severe constipation

• Skin itching and rash

• Painful nerve damage (neuropathy)

• Blood clots

• Birth defects if taken during pregnancy

Lenalidomide common side effects can include:

• Low platelets (thrombocytopenia)

• Constipation or diarrhea

• Skin itching and rash

• Nausea

• Low white blood cells

• Painful nerve damage (neuropathy)

• Blood clots

Pomalidomide common side effects can include:

• Low red blood cells (anemia)

• Low white blood cells

• Nausea

• Nerve damage (not as severe)

• Blood clots

Side effects of targeted therapy medicine

Proteasome inhibitor side effects can include:

• Nausea and vomiting

• Tiredness

• Diarrhea or constipation

• Fever

• Loss of appetite

• Low blood cell counts, especially white blood cells and platelets. This can increase your risk of infection and bleeding and bruising.

• Nerve damage (peripheral neuropathy) that can lead to numbness, tingling, or pain in your hands and feet

Monoclonal antibody side effects can include:

Daratumumab side effects may include:

• Medicine reactions (coughing, wheezing, trouble breathing, runny or stuffy nose, headache, throat tightness, rash, and nausea)

• Tiredness

• Nausea

• Pain in the back

• Fever

• Cough

• Low blood cell counts, which can increase risk of infection and bleeding or bruising

Isatuximab-irfc side effects may include:

• Medicine reaction (coughing, wheezing, trouble breathing, throat tightness, chills, dizziness, headache, rash, and nausea)

• Respiratory infections like pneumonia

• Diarrhea

• Lower white blood cells (risk of infections), lower red blood cells (anemia), and lower platelets (increased risk of bleeding or bruising)

Elotuzumab side effects may include:

• Medicine reaction (coughing, wheezing, trouble breathing, throat tightness, chills, dizziness, headache, rash, and nausea)

• Tiredness

• Decrease in appetite

• Diarrhea

• Constipation

• Cough

• Peripheral neuropathy (numbness and weakness in hands and feet)

• Respiratory infections like pneumonia.

Nuclear export inhibitor side effects may include:

• Low platelet counts (risk of bleeding or bruising)

• Low white blood cell counts (risk of infection)

• Diarrhea

• Nausea and vomiting

• Loss of appetite

• Weight loss

• Respiratory infections like pneumonia

• Low blood sodium levels

Bispecific T-cell engager side effects may include:

• Fever

• Tiredness

• Nausea

• Diarrhea

• Pain in muscles and joints

• Lung infections

• Low blood counts

• Headache

• Cytokine release syndrome (CRS)

• Nervous system problems

CAR-T cell therapy side effects may include:

• Flu-like symptoms

• Diarrhea

• Tiredness

• Infections

• Cytokine release syndrome (CRS)

• Brain-related side effect such as headaches, confusion, or seizures

• Low platelet levels

• Low white blood cell levels

Side effects of corticosteroids

Corticosteroid side effects may include:

• Increased appetite

• Upset stomach

• Weight gain

• High blood sugar levels

• Trouble sleeping

• Feeling like you have too much energy, feeling irritable, changes in mood

• Swelling in hands, feet, and ankles

Side effects of bone-modifying medicines

The side effects of bone-modifying medicines can include:

• Flu-like symptoms

• Muscle and joint aches

• Anemia

• Kidney problems

• Death of bone in the jaw called osteonecrosis (rare but serious)

Working with your healthcare provider

It's important to know which medicines you're taking. Write their names down. Ask your healthcare team how each medicine works and what side effects each might have, and how the manage them.

Talk with your healthcare providers about what signs to look for and when to call them, when to get immediate medical care, and when to call 911. Make sure you know what number to call with questions and concerns. Is there a different number for outside normal office hours, evenings, weekends, and holidays?

It may be helpful to keep a diary of your side effects. A written list will make it easier for you to remember your questions when you go to your appointments. It will also make it easier for you to work with your healthcare team to make a plan to manage your side effects.