A Vaccine for Melanoma Skin Cancer Patients Shows Promise In Reducing the Chances of the Cancer Coming Back By Nearly 50%, Experts Remain ‘Cautiously Optimistic’

Immunotherapy is a treatment that empowers the body’s own immune system to recognize and attack cancer cells.

Dr. George Ansstas, medical oncologist at Siteman Cancer Center at Barnes-Jewish Hospital and WashU Medicine, says the early data suggest that adding this personalized mRNA vaccine to Keytruda could meaningfully improve long-term outcomes for stage 3 and 4 melanoma patients who remain at high risk even after surgery.

Dr. Anna Pavlick is a medical oncologist at Weill Cornell Medicine and Professor of Medicine in the Division of Hematology & Medical Oncology. While hopeful, she remains “cautiously optimistic” about the overall patient survival the personalized vaccine, coupled with immunotherapy, will have.

WATCH: Immunotherapy Needs to be Tailored

“The randomized Phase III trial results are due out soon and will hopefully confirm these findings and demonstrate a survival benefit by the addition of this vaccine,” Dr. Pavick told SurvivorNet.

“This combination reduced the risk of recurrence or death by 49% compared with Keytruda alone, highlighting its potential to significantly improve long‑term outcomes for patients with high unmet needs after surgery,” Dr. Ansstas tells SurvivorNet.

Melanoma begins in melanocytes—the cells that give color to our skin, hair, and eyes. When these cells mutate, they can become aggressive and spread to other organs. While melanoma most often appears on sun-exposed areas like the face, neck, arms, and legs, it can also develop in less obvious places, such as the palms, soles, eyes, mouth, or under the nails.

The Phase 2b KEYNOTE‑942 Trial Explained

The Phase 2b KEYNOTE‑942 trial enrolled 157 patients with high-risk stage 3 or 4 melanoma. After complete surgical removal of their tumors, participants were randomized 2:1 to receive the personalized vaccine plus Keytruda or Keytruda alone. The vaccine was given at 1 mg every three weeks for nine weeks, while Keytruda was administered every three weeks for up to 18 cycles (about one year). The control group received Keytruda alone for the same duration unless recurrence or treatment toxicity occurred.

The study’s primary endpoint was recurrence-free survival (RFS)—the time from the first Keytruda dose until recurrence, a new melanoma, or death. Secondary endpoints included distant metastasis-free survival and safety, with exploratory analyses examining tumor mutational burden (TMB) and its relationship to outcomes.

According to Merck, the combination therapy continued to show “sustained and clinically meaningful improvement” in RFS, reducing the risk of recurrence or death by 49% (HR 0.510; 95% CI 0.294–0.887). The company says it will provide additional follow-up data at an upcoming medical meeting.

Dr. Ansstas says, “The safety profile remained consistent with earlier analyses, supporting its potential integration into standard practice for patients who are disease-free after surgery but still at high risk,” he told SurvivorNet.

Dr. Ansstas added that these early results show this personalized mRNA vaccine could meaningfully strengthen immunotherapy for melanoma—and possibly other cancers—and that larger ongoing trials will help determine which patients benefit most.

How Immunotherapy Like Keytruda Works

Cancer cells often fly under the immune system’s radar by producing proteins that disguise them as “normal.” Checkpoint inhibitors such as Keytruda break that illusion, helping white blood cells recognize and attack those cancer cells.

Rather than killing cancer directly, these treatments empower the immune system to do the job, with fewer side effects on healthy tissue.

WATCH: Immunotherapy Helps Your Body Help Itself

Common side effects of Keytruda include:

• Fatigue
• Rash or itching
• Shortness of breath or cough
• Nausea, vomiting, or appetite loss
• Diarrhea or constipation
• Low thyroid levels
• Abdominal pain

RELATED: Some Melanoma Survivors See Long-Term Side Effects After Immunotherapy Treatment, According to Study

SurvivorNet spoke with the pioneer in immunotherapy research, Dr. James (Jim) Allison at MD Anderson Cancer Center, who was awarded a Nobel Prize for the development of the science called checkpoint inhibitors.

“Immunotherapy is rather unique in that for the first time, we’re getting truly curative therapies in many kinds of disease– not just in melanoma but in lung cancer, kidney cancer, bladder cancer, Hodgkin’s lymphoma, Merkel cell cancer, head and neck cancer,” Dr. Allison tells SurvivorNet.

While it was initially developed for stage 4 melanoma patients, immunotherapy might also be used earlier in the course of the disease. There’s also an immunotherapy cream, Imiquimod (Aldara), used for melanoma in situ (stage 0).

FDA-Approved Immunotherapy for Melanoma

There are several FDA-approved immunotherapies for melanoma. Each is approved for certain instances of melanoma.

• Tebentafusp-tebn (Kimmtrak)
• Aldesleukin (Proleukin)
• Atezolizumab (Tecentriq)
• Dostarlimab (Jemperli)
• Interferon alfa-2b (Intron A)
• Ipilimumab (Yervoy)
• Nivolumab (Opdivo)
• Peginterferon alfa-2b (Sylatron/PEG-Intron)
• Pembrolizumab (Keytruda)
• Talimogene laherparepvec (Imlygic)
• Imiquimod (Aldara)

WATCH: Am I at High Risk for Melanoma?

Immunotherapy Side Effects During Treatment for Melanoma

A recent study published in JAMA Oncology is shedding light on the long-term side effects of immunotherapy in melanoma patients—revealing that chronic complications may be more widespread than previously thought.

“Chronic and long-lasting side effects were more common than we expected and involved a variety of often overlooked organs like the thyroid, salivary glands, and joints,” said Dr. Douglas Johnson, senior author of the study and associate professor of medicine at Vanderbilt University Medical Center.

WATCH: Tell Your Doctor About Immunotherapy Side Effects

Despite the findings, Dr. Johnson emphasized the groundbreaking nature of immunotherapy, especially anti-PD-1 drugs. “It has been an absolute game-changer for patients with melanoma,” he noted. “I think the first thing to recognize is how really transformative the Anti-PD-1 drugs have been… patients can have very long-term responses to treatment.”

Still, for patients with advanced melanoma—especially those who’ve undergone surgical removal and have a low risk of recurrence—Dr. Johnson advised more nuanced conversations around treatment.

“So determining whether the risks of the side effects, weighing the benefits of treatment with the risks of the side effects, can be an important consideration,” he said. “What our study did was we basically saw that some of these side effects were more common, really, than had been previously reported.”

WATCH: Managing Immunotherapy Side Effects

Reported side effects can range from mild to severe, including dry throat, inflammation of the eye blood vessels, numbness, or tingling. And for many, the decision comes down to weighing symptom severity with potential longevity benefits.

Mohs Micrographic Surgery: A Precise Approach to Skin Cancer Treatment

Mohs surgery is the leading method for treating skin cancer on delicate, high-risk areas like the face, ears, and nose. This meticulous technique—known as Mohs micrographic surgery (MMS)—uses microscopic guidance to remove cancerous tissue layer by layer, ensuring that only affected areas are excised while preserving as much healthy skin as possible.

WATCH: The best surgery option for melanoma.

During the procedure, the area is numbed with a local anesthetic. The surgeon carefully removes the visible tumor with a scalpel and immediately examines the tissue under a microscope. If cancer cells remain, the process is repeated—one layer at a time—until all cancerous cells are gone.

This methodical approach offers high cure rates, particularly when cancers are caught early, and minimizes scarring for sensitive, visible areas of the body.

“What is being done is that you’re able to remove a very conservative margin around the cancer and study it in, essentially, real time,” explains Dr. Sumaira Aasi, a professor of dermatology and Director of Mohs and Dermatologic Surgery at Stanford.

“The Mohs surgeon will take a conservative cut circumferentially around the cancer, where we’re able to preserve healthy tissue. We’re able to process the tissue and look at the cancerous tissue and know where there are still tumor cells persisting. As the Mohs surgeon removes the cancer, it’s mapped out.”

Dr. Aasi adds that the surgeon may go back specifically to the areas where the cancer cells were present and take out another conservative margin or amount of cancerous tissue, and repeat the process until the cancer is out completely.

Better Understanding Melanomas

As noted earlier, melanoma starts in the same cells that give your skin, hair, and eyes their color. Changes to a mole you’ve had for a while or a new growth on your skin could be signs of melanoma, according to SurvivorNet’s experts. You’ll want to watch them and tell your doctor about any changes you notice.

WATCH: How do you perform a skin check using the ABCDEs?

SurvivorNet experts recommend avoiding unprotected sun exposure because ultraviolet (UV) radiation can lead to melanoma. Tanning beds pose ultraviolet radiation risks for skin cancer and should be avoided. Many dermatologists recommend using spray tans to reduce the risk of melanoma skin cancer.

The most important thing to look out for when it comes to finding melanoma is a new spot on your skin or a spot that is changing in size, shape, or color, SurvivorNet’s medical experts say.

Treatment options for melanoma include targeted therapy and immunotherapy, which give people a better chance of living a long and healthy life than ever before. If you’re diagnosed with melanoma, there’s a good chance surgery will be the treatment your doctor recommends. Cancer removal usually leads to a cure in the early stages of the disease.

After surgery, the removed tissue and lymph nodes are examined to measure the melanoma and determine if it has clear margins. Clear margins mean the cells around the area of tissue that was removed don’t contain any melanoma. When no cancer cells are left around the removed area, your cancer is less likely to return.

WATCH: Beating Aggressive Melanoma: An Immunotherapy Success Story

Questions to Ask Your Doctor

If you are diagnosed with skin cancer, you may have some questions for your doctor. SurvivorNet suggests some of the following to help you on your cancer journey.

• What type of skin cancer do I have?
• What treatment options exist for my type of melanoma?
• Will insurance cover this treatment?
• Would treatment through a clinical trial make sense for me?
• What resources exist to help manage my anxiety because of this diagnosis?

Learn more about SurvivorNet's rigorous medical review process.

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