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A personalized mRNA vaccine may help reduce the risk of melanoma recurrence, a promising new study finds.
Melanoma is, of course, the deadliest form of skin cancer. According to the American Cancer Society, more than 112,000 new melanomas are likely to be diagnosed in 2026, and 8,510 people are expected to die from the skin cancer variant. It can also be tricky to treat; if you've had one, you are at a higher risk for another, notes the American Academy of Dermatology Association. If melanoma does recur, it typically shows up within five years. Cancerous cells may remain after treatment and can spread to other parts of the body, though it most commonly recurs in the same area.
However, results of the latest clinical trial of a specialized vaccine produced by Moderna and Merck, recently published in the Journal of Clinical Oncology, showed that when combined with traditional melanoma treatment (surgery to remove the cancerous tumors, paired with immunotherapy), the personalized mRNA vaccine could reduce the risk of recurring melanoma.
The trial included 157 people in the United States and Australia with stage 3 melanoma who had a high risk of recurrence. All of the participants were treated with surgery and the immunotherapy medication pembrolizumab, also known as Keytruda, used in certain cancer treatments to help the immune system destroy cancerous cells. A portion of that group—107 patients—was also treated with the vaccine. Known clinically as intismeran autogene, the mRNA-based vaccine is personalized to each patient's tumor using their own DNA, helping to identify and target any possible additional or new cancer cells. Results showed that 68.8% of the patients who received the vaccine stayed skin cancer-free after five years. This is compared to the other group, who were treated with surgery and Keytruda, but no personalized vaccine; 49% of those patients were skin cancer-free after five years.
"In many ways, it represents one of the purest examples of precision medicine currently in clinical development."
According to Deborah S. Sarnoff, MD, a board-certified dermatologist and president of the Skin Cancer Foundation, pembrolizumab/Keytruda is a treatment for patients with resected melanoma, or melanoma that has been surgically removed. “This treatment has been very effective for some patients, but for others, further treatment options are needed,” she says. “If confirmed in larger phase 3 studies, this [immunotherapy plus mRNA vaccine] approach could provide a more personalized treatment option tailored to each patient's tumor mutations.”
Dr. Sarnoff also notes that it could improve long-term outcomes for patients who are at a high risk of recurrence, and even “expand the role of mRNA technology beyond infectious diseases into cancer treatment," possibly becoming a model for personalized vaccines in other cancers. “The results are highly encouraging because the benefits appear durable over five years, which is a meaningful benchmark in melanoma treatment,” she adds.
According to Kavita Mariwalla, MD, a double board-certified dermatologist, Mohs surgeon, and president of the American Society for Dermatologic Surgery, the data is so exciting because “we’re seeing two complementary technologies working together." What distinguishes this personalized, mRNA-based vaccine from earlier cancer vaccines is that “it is not targeting melanoma broadly,” explains Dr. Mariwalla. "It is targeting the unique molecular signature of an individual patient’s tumor. In many ways, it represents one of the purest examples of precision medicine currently in clinical development."
Dr. Mariwalla calls the combo “precision medicine and immunotherapy converging in a way that really signals the future of melanoma therapy," and explains the mechanism of action: "Think of Keytruda as letting off the brakes of the immune system and this vaccine giving your body the GPS to find anything left behind. The idea that you can target something so specifically to prevent recurrence at such an advanced stage is truly remarkable innovation."
In addition, Dr. Mariwalla says that the trial is testing “whether we can use the unique genetic fingerprint of a patient's melanoma to reduce the risk of recurrence,” which makes it “probably the most advanced personalized cancer vaccine ever tested in melanoma. Every dose is uniquely manufactured for a single patient.”
"The idea that you can target something so specifically to prevent recurrence at such an advanced stage is truly remarkable innovation."
Following surgery, the risk of recurrence remains high for patients with stage 3/4 melanoma, "so we are encouraged by these long-term findings showing that intismeran autogene [the vaccine] in combination with Keytruda provided sustained and durable reductions in the risk of recurrence,” Marjorie Green, MD, senior vice president and head of oncology, global clinical development at Merck Research Laboratories, shared in a statement. “These data further reinforce the potential of this individualized approach to address critical gaps…and reflect our continued commitment to advancing innovative therapies for patients.”
More clinical trials are currently under way. “This was a phase 2 study, limited to 157 patients, and the overall survival findings remain exploratory,” notes Dr. Sarnoff. “The ongoing phase 3 trials will be critical for determining whether these promising results translate into a broader patient population and ultimately change clinical practice.”
Dermatologists are optimistic. Valencia D. Thomas, MD, MHCM, professor of dermatology at MD Anderson Cancer Center in Houston, Texas, calls this personalized cancer care “the wave of the future," saying that the trial "combines both the vaccine and the immune-boosting therapies, allowing the body to tag a tumor for destruction while boosting the intensity of the response. It’s like turning the volume up to 11.”
