Immunotherapy for Melanoma Skin Cancer

Immunotherapy is the use of medicines to stimulate a person’s own immune system to recognize and destroy cancer cells more effectively. Several types of immunotherapy can be used to treat melanoma.

Immune checkpoint inhibitors

These newer drugs have shown a lot of promise in treating advanced melanomas. An important part of the immune system is its ability to keep itself from attacking normal cells in the body. To do this, it uses “checkpoints”, which are proteins on immune cells that need to be turned on (or off) to start an immune response. Melanoma cells sometimes use these checkpoints to avoid being attacked by the immune system. But these drugs target the checkpoint proteins, helping to restore the immune response against melanoma cells.

PD-1 inhibitors

Pembrolizumab (Keytruda) and nivolumab (Opdivo) are drugs that target PD-1, a protein on immune system cells called T cells that normally help keep these cells from attacking other cells in the body. By blocking PD-1, these drugs boost the immune response against melanoma cells. This can often shrink tumors and help people live longer (although it’s not yet clear if these drugs can cure melanoma).

These drugs are given as an intravenous (IV) infusion every 2 or 3 weeks.

Side effects of these drugs can include fatigue, cough, nausea, itching, skin rash, decreased appetite, constipation, joint pain, and diarrhea.

Other, more serious side effects occur less often. These drugs work by basically removing the brakes from the body’s immune system. Sometimes the immune system starts attacking other parts of the body, which can cause serious or even life-threatening problems in the lungs, intestines, liver, hormone-making glands, kidneys, or other organs.

It’s very important to report any new side effects to your health care team promptly. If serious side effects do occur, treatment may need to be stopped and you may get high doses of corticosteroids to suppress your immune system.

CTLA-4 inhibitor

Ipilimumab (Yervoy) is another drug that boosts the immune response, but it has a different target. It blocks CTLA-4, another protein on T cells that normally helps keep them in check.

This drug is given as an intravenous (IV) infusion, usually once every 3 weeks for 4 treatments. In patients with melanomas that can’t be removed by surgery or that have spread to other parts of the body, this drug has been shown to help people live longer, although it’s not clear if it can cure the melanoma.

The most common side effects from this drug include fatigue, diarrhea, skin rash, and itching.

Serious side effects seem to happen more often with this drug than with the PD-1 inhibitors. Like the PD-1 inhibitors, this drug can cause the immune system to attack other parts of the body, which can lead to serious problems in the intestines, liver, hormone-making glands, nerves, skin, eyes, or other organs. In some people these side effects can be life threatening.

It’s very important to report any new side effects during or after treatment to your health care team promptly. If serious side effects do occur, you may need to stop treatment and take high doses of corticosteroids to suppress your immune system.

Cytokines (interferon-alfa and interleukin-2)

Cytokines are proteins in the body that boost the immune system in a general way. Man-made versions of cytokines, such as interferon-alfa and interleukin-2 (IL-2), are sometimes used in patients with melanoma. They are given as intravenous (IV) infusions, at least at first. Some patients or caregivers may be able to learn how to give injections under the skin at home.

For advanced melanomas: Both interferon-alfa and IL-2 can shrink advanced melanomas in about 10% to 20% of patients when used alone. These drugs may also be given along with chemotherapy drugs (known as biochemotherapy) for stage IV melanoma.

Side effects can include flu-like symptoms such as fever, chills, aches, severe tiredness, drowsiness, and low blood cell counts. Interleukin-2, particularly in high doses, can cause fluid to build up in the body so that the person swells up and can feel quite sick. Because of this and other possible serious side effects, high-dose IL-2 is given only in the hospital, in centers that have experience with this type of treatment.

After surgery for some earlier-stage melanomas: Thicker melanomas are more likely than thinner melanomas to come back in another part of the body after surgery, even if all of the cancer is thought to have been removed. Interferon-alfa can sometimes be used as an added (adjuvant) therapy after surgery to try to prevent this. This may delay the recurrence of melanoma, but it’s not yet clear if it improves survival.

High doses must be used for the interferon to be effective, but many patients can’t take the side effects of high-dose therapy. These can include fever, chills, aches, depression, feeling very tired, and effects on the heart and liver. Patients getting this drug need to be watched closely by a doctor who is experienced with this treatment.

When deciding whether to use adjuvant interferon therapy, patients and their doctors need to take into account the potential benefits and side effects of this treatment.

Oncolytic virus therapy

Viruses are a type of germ that can infect and kill cells. Some viruses can be altered in the lab so that they infect and kill mainly cancer cells. These are known as oncolytic viruses. Along with killing the cells directly, the viruses can also alert the immune system to attack the cancer cells.

Talimogene laherparepvec (Imlygic), also known as T-VEC, is an oncolytic virus that can be used to treat melanomas in the skin or lymph nodes that can’t be removed with surgery. The virus is injected directly into the tumors, typically every 2 weeks. This treatment can sometimes shrink these tumors, but it hasn’t been shown to shrink tumors in other parts of the body. It’s also not clear if this treatment can help people live longer. Side effects can include flu-like symptoms and pain at the injection site.

Bacille Calmette-Guerin (BCG) vaccine

BCG is a germ related to the one that causes tuberculosis. BCG doesn’t cause serious disease in humans, but it does activate the immune system. The BCG vaccine is sometimes used to help treat stage III melanomas by injecting it directly into tumors.

Imiquimod cream

Imiquimod (Zyclara) is a drug that is put on the skin as a cream. It stimulates a local immune response against skin cancer cells. For very early (stage 0) melanomas in sensitive areas on the face, some doctors may use imiquimod if surgery might be disfiguring. It can also be used for some melanomas that have spread along the skin. Still, not all doctors agree it should be used for melanoma.

The cream is usually applied 2 to 5 times a week for around 3 months. Some people have serious skin reactions to this drug. Imiquimod is not used for more advanced melanomas.

Newer treatments

Some other types of immunotherapy have shown promise in treating melanoma in early studies. At this time they are available only through clinical trials (see What’s New in Melanoma Skin Cancer Research?).

To learn more about this type of treatment, see Cancer Immunotherapy.

The American Cancer Society medical and editorial content team

Our team is made up of doctors and oncology certified nurses with deep knowledge of cancer care as well as journalists, editors, and translators with extensive experience in medical writing.

Last Medical Review: May 19, 2016 Last Revised: May 20, 2016

American Cancer Society medical information is copyrighted material. For reprint requests, please see our Content Usage Policy.