Connie Franciosi, 80, noticed a suspicious spot on her skin and was diagnosed with melanoma in 2020. "It was considered a late diagnosis," she says.
The skin cancer can be difficult to treat if it's not detected and treated early, and it can spread to other parts of the body. There are approximately 112,000 melanomas diagnosed in the U.S. each year and about 8,500 deaths.
After Franciosi had surgery to remove the melanoma, she was told she had a high risk of recurrence and was offered a spot in a clinical trial testing a new messenger RNA (mRNA) vaccine combined with Keytruda, an immunotherapy drug.
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At the time, mRNA technology was in the news because of the recently developed Moderna COVID-19 vaccine. This melanoma trial, which included 157 patients in Australia and the U.S., all of whom had surgery to remove their tumors, was set up to test whether the same mRNA technology could be used to create a personalized cancer vaccine, explains Dr. Janice Mehnert. Mehnert is a melanoma specialist and researcher at NYU Langone Health and senior author of a new paper published Monday analyzing the five-year results.
"This is an incredibly interesting trial because the approach is just so unique," Mehnert says. "It is a personalized immunotherapy strategy," tailored to each patient's tumor.
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The results are striking. After five years of follow-up, 68.8% of patients who received the combination therapy remained cancer-free, she says, compared with 49.1% of patients who received Keytruda alone, which amounts to a 49% reduction in risk. "That's pretty exciting," Mehnert says.
In addition, 92% of patients who received the combination therapy were alive at the five-year mark, compared with 71% of those who only used Keytruda. "I think this is strong evidence that this therapy, when used in combination with immunotherapy, can demonstrably reduce the risk of dying from this disease," she says.
The results of the study are being presented at the American Society of Clinical Oncology conference today and are published in the Journal of Clinical Oncology.
Mehnert says that predicting when melanoma will recur is difficult.
"Sometimes recurrence is easily treated with surgery or radiation, but sometimes it happens in the lungs, the liver or the brain," and then it can be challenging to treat, she says. That's why a preventive approach makes sense. "We're trying to harness the power of the immune system early in a patient's disease course to optimize their outcomes," she says.
Dr. Sarah Arron, a dermatologist and skin cancer surgeon in the San Francisco Bay Area who was not involved in the research, says the results are significant and demonstrate the potential of mRNA vaccines.
"I think this is a landmark advance in how we treat these very advanced, high-risk melanomas," she says.
Arron notes that while Americans became familiar with mRNA technology through the COVID-19 vaccine, this application is fundamentally different.
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"The COVID vaccine was the same RNA fragment given to everybody. Whereas in this case, the antigen itself is not one virus, it's [each] patient's tumor," she says. Since each person's melanoma can differ, each vaccine is tailored. "By matching this RNA treatment to the patient's melanoma, we can really boost the immunotherapy by driving it toward the patient's tumor."
How the combination works
Cells in the immune system, known as T cells, are built to find and destroy threats like cancer, but cancer can be sneaky, putting up the equivalent of a "don't attack me" shield that hides them. To simplify, Keytruda works by lifting that shield so T cells can see the cancer again. The personalized mRNA vaccine then amplifies the effect.
Scientists sequence a patient's tumor to identify up to 34 unique molecular fingerprints called neoantigens and encode them into a custom vaccine. When it's injected, the vaccine trains T cells to recognize and target those specific neoantigens, giving the immune system a blueprint for attacking the cancer. So, each patient's tumor informs the vaccine that they will receive.
In the trial, side effects were mild, including chills and minor pain at the injection site.
Arron says that given the reservations and politicization of the COVID-19 vaccine, it's important to understand how this technology works. "This mRNA vaccine is designed towards boosting a tumor response," she says. And the results are "very encouraging" for the use of mRNA.
Researchers are also studying whether mRNA vaccines can be used to prevent the recurrence of other cancers, including lung cancer.
The next steps
"The results are exciting," says Moderna's chief development officer, Dr. David Berman. The company developed the vaccine, which is called intismeran, and is collaborating with Merck, the maker of pembrolizumab, which is marketed under the trade name Keytruda.
A Phase 3 trial is now underway, which includes nearly 1,000 patients. Once results are analyzed in the coming months, the goal is to seek FDA approval, Berman says.
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Berman has been working on melanoma for many years, before joining Moderna, so he says this feels like a momentous step forward.
"The degree of benefit was incredible," Berman says, pointing to the significant reduction in risk of recurrence.
For Connie Franciosi, the results speak for themselves. "I am cancer-free." She says her scans have shown no recurrence. "Life is good."
She recently celebrated her 80th birthday. Her days are packed with the things she loves, including tending her gardens, staying active with her local library, and gathering with friends and playing golf.
"I have some good shots and some not-so-good shots, but I just enjoy the game," she says. "I have a very satisfying life."
Transcript
JUANA SUMMERS, HOST:
The same technology used to make COVID vaccines has now led to a new advance in fighting skin cancer. A study published today in the Journal of Clinical Oncology finds an mRNA vaccine is very effective at preventing a recurrence of melanoma when used in combination with Keytruda, an immunotherapy drug. NPR's Allison Aubrey reports.
ALLISON AUBREY, BYLINE: Connie Franciosi recently celebrated her 80th birthday and says her days are packed with things that she loves to do - working in her garden, staying active with her local library, gathering with friends and playing golf.
CONNIE FRANCIOSI: I have some good shots and some not-so-good shots, but just enjoy the game, and life is good.
AUBREY: Life is good. She does not take her health for granted. Six years ago, she was diagnosed with melanoma, a skin cancer that can be deadly if not detected and treated.
FRANCIOSI: And it was considered a late diagnosis, so when they did the surgery, it had spread.
AUBREY: She was at high risk of recurrence and was told to watch and wait, but it was more like watch and worry. Luckily, she learned about a new clinical trial to test a vaccine made with messenger RNA technology combined with an immunotherapy drug called Keytruda. Nearly six years later, her scans show she is cancer-free. Her experience fits with the findings of the new study out today. Dr. Janice Mehnert, a melanoma expert at NYU, is senior author of the study.
JANICE MEHNERT: And so after five years of follow up, 68.8% of patients who took the combination therapy remained cancer-free.
AUBREY: And 92% were still alive. So the treatment is more effective than immunotherapy alone and seems to significantly reduce the risk of death from melanoma. And Mehnert says the approach used in this trial is unique.
MEHNERT: It is a vaccine that, yes, uses mRNA technology, but even more innovative, it is a personalized immunotherapy strategy that's informed by the patient's own tumor.
AUBREY: To make the vaccine, scientists sequence a patient's tumor to identify up to 34 molecular fingerprints called neoantigens and then encode them into a custom vaccine.
MEHNERT: We're trying to harness the power of the immune system early.
AUBREY: When the vaccine is injected, the idea is that it trains the immune cells, known as T cells, to recognize and target those specific antigens, giving the immune system a blueprint to attack the cancer. Dr. Sarah Arron (ph) is a dermatologist and skin cancer surgeon who was not involved in the research.
SARAH ARRON: I think this is a landmark advance in how we treat these very advanced high-risk melanomas because for the first time, we're doing immunotherapy with a personalized mRNA to boost the immune response to the patient's unique tumor.
AUBREY: The COVID mRNA vaccine was the same for everyone, but she says, with this new cancer vaccine, it's possible to be much more targeted.
ARRON: Everybody's melanoma is a little bit different, and so by matching this mRNA treatment to the patient's melanoma, we can really boost the immunotherapy.
AUBREY: The vaccine was developed by Moderna, and the clinical trial was conducted with the pharmaceutical company Merck, which markets Keytruda the immunotherapy drug. A phase 3 trial that includes nearly 1,000 people is underway, and once they have results in the coming months, the goal is to seek FDA approval, explains Moderna's chief development officer, Dr. David Berman. He says the results are very exciting for the company.
DAVID BERMAN: It's the first time ever in a randomized trial that a cancer vaccine has ever demonstrated a positive result. And the degree of benefit was incredible.
AUBREY: He says Moderna's pipeline is full with more research into vaccines for types of lung, kidney and bladder cancer. Allison Aubrey, NPR News.