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Immunotherapy and Melanoma

Right now, immunotherapy for melanoma is given only to people whose tumors have spread or metastasized. If you are interested in immunotherapy, talk with your doctor about your options, including a clinical trial.

Types of Immunotherapy

Cytokines

Older approaches to immunotherapy attempted to boost the body’s natural defense system in a general way. Drugs such as interferon and interleukin shrink tumors in about 10-20% of melanoma patients, but the responses often last for only a short time. Interferon and interleukin may also be given with chemotherapy.

The side effects of cytokines are fever, chills, severe tiredness, drowsiness and body aches. As new forms of immunotherapy have emerged, cytokines are used less, although they are still effective for some people with advanced melanoma.

Ipilimumab (Yervoy®)

The introduction of ipilimumab or “ipi” was a huge step forward in treating advanced melanoma. A high percentage of people with metastatic melanoma respond to this drug. We now know cancer cells can block the ability of the immune system to recognize and destroy them—much like slamming the brakes on the immune system.

Ipilimumab works by removing those brakes. While ipi has helped people with advanced melanoma live longer and have a higher quality of life, it is not a cure. Virtually all people become resistant to the drug after a period of six to 18 months and the disease comes back. Researchers are now doing clinical trials with other drugs to see if combining these agents can overcome this problem.
One unusual characteristic of ipi and similar drugs is some people actually seem to get worse before they get better. Existing tumors sometimes grow and new ones appear before the positive response takes place. This delayed response can pose difficult challenges for people who want to know if their treatment is working or not.

Although response to treatment is usually defined as having the tumor shrink or disappear, ipi can produce a long period of time in which the cancer is stable—it doesn’t get smaller or larger.

The side effects of ipi include fatigue, diarrhea, skin rash and itching. Some people can have side effects that are more serious.

PD-1 Inhibitors

There is a lot of excitement today about an emerging category of drugs called PD-1 inhibitors. Researchers have learned cancer cells, including melanoma cells, can produce, or express PD-1. Doing this allows them to hide from the body’s immune response by inactivating T cells, which attack foreign or abnormal cells. PD-1 inhibitors block the cancer cells’ ability to produce PD-1 and allow the T cells to find and destroy the melanoma cells.

The side effects of PD-1 inhibitors include fatigue, rash, itching and diarrhea.

Clinical trials using PD-1 inhibitors have shown promising results in people with advanced melanoma. Over a third of individuals responded to this treatment. Many of the responses were long lasting, continuing for a year or more. Even people who have become resistant to ipilimumab respond to PD-1 inhibitors.

In 2014, the U.S Food and Drug Administration (FDA) approved two PD-1 inhibitors for use with people who have advanced melanoma and are no longer responding to other drugs. The drugs are pembrolizumab (Keytruda®) and nivolumab (Opdivo®).

The Future of Immunotherapy for Melanoma

Almost all immunotherapy treatment options are available only by participating in clinical trials. These studies compare the best known treatments to new approaches and are essential to understanding whether the new drugs are safe and effective.

In addition, researchers are also interested in learning:

  • Which people benefit from these treatments.
  • Why some people do not respond.
  • The best time to give immunotherapy in the treatment plan.
  • How immunotherapy can be combined with other drugs and treatments to maximize its benefits and minimize side effects.
  • How long treatments should continue.
  • The long-term effects of immunotherapy.

These are all important questions that can only be answered in clinical trials by doctors and researchers who have expertise and experience in treating melanoma.

The field of immunotherapy for treating people with melanoma, especially those with widespread disease, is moving very fast. Many melanoma experts now regard immunotherapy as critical to treating people with advanced melanoma.

In the next few years, expect to see progress in the use of immunotherapy for advanced melanoma—a cancer that was at one point almost impossible to treat.