Melanoma: Immunotherapy

When might immunotherapy be used for melanoma?

Your healthcare provider may suggest immunotherapy if one of these cases applies to you:

• You have advanced melanoma. In this case, the goal of immunotherapy is to help shrink the tumor and improve survival (length of life). Your healthcare provider may also suggest a clinical trial of a new immunotherapy medicine that could help you.

• You need it to pretreat the melanoma before surgery. Immunotherapy before surgery may stimulate your immune system to attack any tumor that's already spread or is left behind after surgery. Immunotherapy used before surgery is called neo-adjuvant therapy.

• You have had surgery to remove the melanoma, but you are at higher risk for it coming back. Immunotherapy used after surgery is called adjuvant therapy. It may help lower the risk that the cancer will come back. Or it may delay the amount of time before the cancer comes back. It may also help some people live longer.

What types of immunotherapy can be used to treat melanoma?

The types of immunotherapy medicines used for melanoma include:

• Anti-PD-1 therapy

• Anti-CTLA-4 therapy

• Anti-LAG3 therapy

• Cytokine therapy (interferon alpha, interleukin-2)

• Intratumoral vaccine therapy

Anti-PD-1 therapy

Pembrolizumab and nivolumab are medicines that use antibodies to block the PD-1 protein on immune cells. They are called PD-1 inhibitors. They help the immune system attack melanoma cells. These medicines are given as an IV (intravenous) infusion every 2 to 6 weeks.

Common side effects can include:

• Cough

• Feeling tired

• Nausea

• Skin rash

• Itching

• Loss of appetite

• Constipation

• Joint pain

• Diarrhea

These medicines can also allow the immune system to attack other cells in your body. This can lead to less common but more serious side effects. These include damage to the lungs, liver, intestines, kidneys, hormone-making glands, and other organs. It's important to report any side effects to your healthcare provider right away.

Anti-CTLA-4 therapy 

Ipilimumab is a medicine that uses an antibody to target a protein on immune cells called CTLA-4. The CTLA-4 protein may help melanoma cells survive, so targeting it boosts the immune system to help fight melanoma. This medicine is used to treat advanced melanoma. It can also be used after surgery for some melanomas that have reached the lymph nodes. This will help lower the risk that they will come back. It is given as an IV infusion, usually once every 3 weeks. Ipilimumab is most commonly given with nivolumab for unresectable (surgery isn't a treatment choice) or metastatic melanoma (when the cancer spreads to other organs) in adults and children 12 years of age and older.

Side effects of the medicine can sometimes be severe. In some cases the immune system may attack other parts of the body. It may attack the intestines, liver, nerves, skin, eyes, glands that make hormones, or other organs. These problems seem to occur more often with ipilimumab than with the anti-PD-1 medicines. They can lead to serious or even life-threatening symptoms. Other side effects can include:

• Feeling tired

• Skin rash

• Itching 

• Diarrhea

• Allergic reactions during medicine infusion 

It's important to report any side effects to your healthcare provider right away.

Anti-LAG-3 therapy (combined with Anti-PD-1 therapy)

Relatlimab-rmbw targets LAG-3 (lymphocyte activation gene 3) protein on the surface of some immune cells. It normally helps keep the immune system in check. It is combined with the PD-1 inhibitor nivolumab into one medicine. Targeting LAG-3 along with PD-1 can help restore immune cell function and increase your immune system's ability to target and kill cancer cells.

It is given as an IV infusion every 4 weeks. It is used to treat melanomas that can't be removed by surgery or have spread to distant parts of the body for adults and children 12 years of age or older.

Side effects of the medicine include the side effects given for anti-PD-1 therapy. There may also be changes in skin color and allergic reactions during medicine infusion. It's important to tell your healthcare provider of any side effects right away.

Cytokine therapy

Cytokines are proteins that set off your immune system. Two cytokines used to treat melanoma are:

• Interferon-alpha

• Interleukin-2 (IL-2)

Healthcare providers use medicines with cytokines to boost general immunity. For example, the interleukin-2 cytokine helps the growth of certain white blood cells. These medicines are given by IV or as injections.

Side effects from cytokine therapy can be serious, and can include:

• Fever

• Chills

• Aches

• Depression

• Low blood cell counts

• Fatigue (severe tiredness)

• Stomach upset

• Vomiting

• Diarrhea

• Fluid buildup in the body

Some side effects are specific to certain cytokines. For example, high doses of interleukin-2 can cause low blood pressure and large amounts of fluid to build up in the body. High doses of interferon alpha can cause more severe forms of many of the side effects above, as well as effects on the heart and liver. People getting these treatments often need to be watched closely, so treatment might need to be given in the hospital. Some people can't take the high doses needed for treatment. But side effects usually get better after the treatment is done.  

Intratumoral vaccine therapy

Special types of vaccines can be injected directly into some melanoma tumors. This can help to shrink them. These include:

• Talimogene laherparepvec. This is a type of virus that is used for melanomas that can't be removed by surgery. It can be injected into tumors on the skin or in lymph nodes. The virus can kill cancer cells and help boost the immune response against the cancer cells. It can shrink some tumors, but it is not clear if it can help people live longer. Side effects can include pain at the injection site and flu-like symptoms. 

• Bacille Calmette-Guerin (BCG). This vaccine is rarely used to treat melanoma but might be a choice. BCG is a vaccine derived from a bacteria closely related to the one that causes tuberculosis. BCG does not cause serious disease in humans, but it does make the immune system active. The BCG vaccine can work like a cytokine, boosting the entire immune system. It can be used to help treat melanoma by injecting it directly into a tumor.

Other types of vaccines that target melanoma cells are being tested in clinical trials. The most common types of vaccines are pieces of proteins called peptides, and dead cancer cells. These may be injected under the skin with other immune boosters. The theory is that they may create an immune reaction in the body to the vaccine that will also work against the cancer cells.

Talking with your healthcare provider

Make sure to talk with your healthcare provider about these medicines and their effects. They will talk with you about the risks and benefits. You can also ask about clinical trials. You may be eligible for a clinical trial that tests a new medicine.