Immunotherapy for Metastatic Melanoma: What’s Available?

Medically Reviewed by Sabrina Felson, MD on August 25, 2020

Melanoma is the most serious form of skin cancer. It’s also an immune responsive disease, which means if you have melanoma, your body’s protective immune system is going into attack mode.

For a few people, that natural reaction is enough to destroy a tumor. Most of the time, though, that isn’t the case.

But imagine if you could flip a biological switch to turn your immune system into a trained assassin that seeks and destroys only melanoma tumors, leaving healthy cells alone. That’s the basic idea behind immunotherapy.

Early stage melanomas can be cured with surgery. More advanced melanomas (those that have metastasized, or spread to different body parts) are tougher to treat.

Historically, there haven’t been many successful options for metastatic melanoma. But new types of immunotherapy are bringing new hope to people with this type of cancer disease.

Your Body, Your Battlefield

Your immune system is a mix of organs, cells, and other things that help protect your body from hostile invaders, like infections and diseases. When it doesn’t recognize a new substance in your body, it sounds the alarm and attacks the invader.

But cancer cells are hard for the immune system to keep tabs on. It may not spot them because they look a lot like normal cells. Sometimes it sees the cancer cells but can’t respond strongly enough to kill them. Also, cancer cells can send out signals that keep your immune system in check.

Immunotherapy uses medicine to help your body fight cancer in two basic ways:

  • Kick-starts your immune system so it does a better job of finding and fighting cancer cells
  • Boosts your natural defenses with man-made versions, like immune system proteins made in a lab

Immunotherapy has become a huge weapon in the war on cancer. Newer treatments are sure to impact how cancers are treated in the future.

What’s in the War Chest?

Right now, immunotherapy is mostly used for people with metastatic melanoma, or those who may have a high chance of the cancer coming back. Options include:

Immune checkpoint inhibitors: These promising new drugs use “checkpoints” -- proteins on immune cells that need to be switched on or off to start or boost the immune response. They also help prevent your immune system from attacking normal, healthy cells. There are two types:

  • PD-1 inhibitors: nivolumab (Opdivo) and pembrolizumab (Keytruda)
  • CTLA-4 inhibitor: ipilimumab (Yervoy)

Targeted therapy: 

  • BRAF inhibitors: About half of melanomas are associated with a mutated or activated BRAF gene. The FDA has approved three BRAF inhibitors to treat melanoma - dabrafenib (Tafinlar), encorafenib (Braftovi), and vemurafenib (Zelboraf).
  • MEK inhibitors: These attack the MEK protein, which is involved in cancer spread. They work well in combination with BRAF inhibitors to shrink tumors and delay tumor growth. Drugs include trametinib (Mekinist), cobinmetinib (Cotellic), and binimetinib (Mektovi). 

These drugs also work in combination with PD-1 inhibitors. 

Cytokines: An older approach to immunotherapy, these are proteins that rev up your immune system. Man-made cytokines, like interferon-alfa and interleukin-2, can shrink tumors, but these are typically short-term responses. You might get them along with chemotherapy drugs.

Oncolytic virus therapy: These viruses can be programmed in the lab to infect and kill cancer cells, while they alert the immune system to act as a reinforcement. T-vec (Imlygic) is a genetically modified virus designed to replicate within tumors and make them rupture.

Bacille Calmette-Guerin (BCG) vaccine: This germ is related to the one that causes tuberculosis. It won’t cause serious problems, but it will wake up your immune system and is sometimes used to help treat stage III melanomas.

Strength in Numbers

These treatments work when they’re used alone, but doctors have also found that a combination will yield greater results.

The FDA has approved combination immunotherapy for metastatic melanoma including a mix of CTLA-4 inhibitor ipilimumab (Yervoy) and a the PD-1 inhibitor nivolumab (Opdivo) or pembrolizumab (Keytruda).

The results are good. Combining treatment with a PD-1 inhibitor and ipilimumab had better survival rates than treating with ipilimumab alone. In some cases, the disease had nearly disappeared.

Discuss all treatment options, and their side effects, with your doctor. They can help decide what might work best for you. Things to think about: your age and overall health, the stage of your cancer, the chances that treatment will help, and how you feel about the potential side effects.

Right now, immunotherapy is the standard of care for people with metastatic melanoma. Most people get it by taking part in clinical trials. Doctors use these to test medications before they go to market. If you’re interested in exploring this state-of-the-art treatment, ask your doctor.

Metastatic melanoma used to be virtually untreatable, an unfair flip of the coin. But research is moving fast, and doctors expect continued progress in the use of immunotherapy for metastatic melanoma in the next few years.

Show Sources


Melanoma International Foundation: “Melanoma Treatment: Stage IV.”

Cancer Support Community: “Frankly Speaking About Cancer: Your Immune System and Melanoma.”

American Cancer Society: “Immunotherapy for melanoma skin cancer,” “Melanoma skin cancer treatment,” “What is cancer immunotherapy?” “What’s new in melanoma skin cancer research?”

Melanoma Research Foundation: “Melanoma Treatment -- Immunotherapy.”

John Hopkins Medicine: “The Final Frontier? Immune Therapies Break Through Cancer’s Protective Barriers.”

Memorial Sloan Kettering Cancer Center: “Immunotherapy Combination Nivolumab Plus Ipilimumab Receives FDA Approval for Metastatic Melanoma.”

Medscape: “Malignant Melanoma Treatment Protocols.” "Melanoma: Types of Treatment."

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