How Immunotherapy Is Improving Treatment for Melanoma

One reason cancer has historically been so difficult to treat is that cancer cells can basically hide from the body’s immune system. Normally, your immune system helps recognize foreign threats within the body, such as viruses or allergens, and sends immune cells to attack.

When affected by cancer, however, the immune system is “highly suppressed” and unable to detect and attack cancer cells, according to Jeffrey Weber, MD, PhD, medical oncologist and melanoma researcher at Perlmutter Cancer Center at NYU Langone Health.

In the past, oncologists would use radiation therapy (which uses X-rays to kill cancer cells) or chemotherapy (which attacks any rapidly dividing cell in the body) to treat metastatic melanoma, an advanced stage of the most dangerous form of skin cancer. However, a newer type of treatment known as immunotherapy uses the body’s immune system itself to fight cancer cells caused by melanoma.

Immunotherapy as an Adjuvant Treatment

Metastatic melanoma refers to the most advanced stage of the disease, when melanoma cells have spread beyond the skin to lymph nodes and other organs. Because the melanoma is circulating in the blood and affecting other parts of the body, surgical excision of the melanoma tumor isn’t enough to rid the body of cancer cells and reduce the risk of melanoma recurrence.

“We can’t just focus on this one area, and say by managing this one area we got this tumor under control,” says Kaveh Alizadeh, MD, melanoma surgeon. “Once it’s metastasized, the chances of those tumors appearing in different places becomes higher, so now we have to go after the entire thing.”

To treat the melanoma that has metastasized within the body, oncologists turn to more conventional forms of cancer treatment. This step is known as adjuvant therapy. The most common method of adjuvant therapy for metastatic melanoma is immunotherapy.

Immunotherapy is a group of treatments that rev up the body’s immune system to help detect and target cancer cells. It is more precise than previous cancer treatments (like radiation therapy and chemotherapy), and it causes fewer side effects.

What Are Checkpoint Inhibitors?

There are different types of immunotherapy, but the one used to treat metastatic melanoma is called checkpoint inhibitors.

Here’s how it works: The immune system uses a “checkpoint” system, in which proteins on an immune cell can be switched on or off  to trigger—or inhibit—the immune response. Melanoma and other cancer cells can manipulate this checkpoint system to turn off the immune response, allowing rapid and uninhibited cancer growth.

That’s where checkpoint inhibitors come in. They block those proteins on the immune cell, signalling to the immune system to recognize and attack the melanoma cells.

There are two main types of checkpoint inhibitors for treating melanoma:

• PD-1 inhibitors target a protein on the immune cells called PD-1. This type of checkpoint inhibitor has been shown to be more effective and less toxic than CTLA-4 inhibitors, cutting risk of relapse by a third, according to clinical trials led by Dr. Weber at NYU Langone.

• CTLA-4 inhibitors target a protein on the immune cells called CTLA-4. It is used less frequently than PD-1 inhibitors but may be useful in certain patients who did not respond to PD-1 inhibitors, according to UpToDate from Wolters Kluwer.

Immunotherapy is still a young type of cancer treatment, so even though it has greatly improved treatment for many types of cancer, it is still uncertain if it can “cure” metastatic melanoma (i.e., prevent relapse).

Dr. Weber conducted the pilot study on immunotherapy for metastatic melanoma. In the study, the patients had high risk of melanoma recurrence. After six years of follow up, “fewer than half those patients ever relapsed, which is good,” says Dr. Weber.