This type of adjuvant therapy attacks cancer cells more precisely.
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.
Dr. Weber is a medical oncologist, melanoma researcher, and the deputy director of the Perlmutter Cancer Center at NYU Langone Health.Kaveh Alizadeh
Dr. Alizadeh is a board-certified plastic surgeon and the chief of plastic and reconstructive surgery at Westchester Medical Center and New York Medical College.
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Immunotherapies are drugs that in
general disinhibit the immune system,
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which is highly suppressed in melanoma and
many other cancers.
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Both in the host, in the patient,
and directly in the tumor,
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what we call the tumor microenvironment.
00:00:17,100 --> 00:00:21,053
So in cancer, the immune system's so
suppressed that cutting that brake cable
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provides major benefit in melanoma and
many other cancers, too.
00:00:24,366 --> 00:00:29,840
00:00:29,840 --> 00:00:31,935
We can't just focus on one area, and
00:00:31,935 --> 00:00:36,230
saying by managing this one area
we got this tumor under control.
00:00:36,230 --> 00:00:38,110
Once it's metastasized,
00:00:38,110 --> 00:00:41,470
the chance of this tumor appearing
in different places becomes higher.
00:00:41,470 --> 00:00:43,249
So now we have to go
after the entire thing.
00:00:44,270 --> 00:00:47,440
And as we get to more and
more distant metastasis,
00:00:47,440 --> 00:00:48,900
we have to think systematically.
00:00:48,900 --> 00:00:50,860
Systematically means the entire body.
00:00:50,860 --> 00:00:54,320
We can't just focus on one area,
and as we're learning more and
00:00:54,320 --> 00:00:59,040
more, we can actually do these very
specific cell-mediated treatments.
00:00:59,040 --> 00:01:03,220
Where we're really seeking
out these bad tumors, and
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allowing the immune system to
go after them, and get them.
00:01:06,720 --> 00:01:09,520
That's the good news for
people that have later stage
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melanomas is they have more potential for
disease free survival.
00:01:13,870 --> 00:01:17,780
And more potential with some of these
newer treatments that are out there to
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target their immune system to
fight the tumors for them.
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After the surgeon does his or
her thing, and
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they remove the tumor,
clinically it's gone.
00:01:27,340 --> 00:01:31,010
But we all know that melanoma,
depending on how thick it is and
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how many different qualities it has,
00:01:33,300 --> 00:01:37,400
can have a very risk of relapse even
after the surgeon takes it out.
00:01:37,400 --> 00:01:41,370
So adjuvant therapy is what we
add after surgery to decrease
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the chance that that tumor will return or
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The adjuvant immunotherapy for melanoma
was actually piloted interestingly by me,
00:01:50,010 --> 00:01:54,730
back seven or eight years ago, and clearly
showed that the patients did very well.
00:01:54,730 --> 00:01:58,460
We treated 33 some odd patients
who had very high-risk disease,
00:01:58,460 --> 00:02:00,450
more than a 50% risk of relapse.
00:02:01,460 --> 00:02:04,381
And with, geez, six years of follow up,
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fewer than half of those patients
ever relapsed, which is good.
00:02:08,983 --> 00:02:13,160
Adjuvant therapy for cutaneous melanoma. Waltham, MA: UpToDate, 2019. (Accessed on December 15, 2021 at https://www.uptodate.com/contents/adjuvant-therapy-for-cutaneous-melanoma.)
CBS News: immunotherapy drug proves to be better than competitor in treating advanced melanoma. New York, NY: NYU Langone, 2017. (Accessed on December 15, 2021 at https://nyulangone.org/news/cbs-news-immunotherapy-drug-proves-be-better-its-competitor-treating-advanced-melanoma.)
Immunotherapy for melanoma skin cancer. Atlanta, GA: American Cancer Society. (Accessed on December 15, 2021 at https://www.cancer.org/cancer/melanoma-skin-cancer/treating/immunotherapy.html.)What is melanoma? New York, NY: Skin Cancer Foundation. (Accessed on December 15, 2021 at https://www.skincancer.org/skin-cancer-information/melanoma.)