- Different stages of melanoma have a higher risk of the skin cancer coming back after being surgically removed.
- An experimental therapy developed by Merck and Moderna aims to help lower the recurrence rate in people with completely resected stage IIB-IV melanoma.
- Participants in the clinical study of their new mRNA-based treatment experienced a 49% reduction in melanoma recurrence or death.
In 2022, about 330,000 people around the world were diagnosed with the skin cancer melanoma, with about 60,000 people dying from the condition.
Different stages of melanoma have a higher risk for recurrence — coming back after being surgically removed. For instance, past studies show that stage III melanoma carries a high recurrence risk of 40% to as much as 90% at five years following surgery.
On August 19, pharmaceutical companies Merck and Moderna announced the phase 3 clinical study results for an experimental therapy designed to help lower the recurrence rate in people with stage IIB-IV melanoma who have had their tumor completely removed.
Medical News Today spoke with seven melanoma experts to find out more about this potential new treatment and how it may help lower recurrence risk in people with higher stages of melanoma.
According to Joan Levy, PhD, chief science officer of the Melanoma Research Alliance, “completely resected” means surgeons have successfully removed all melanoma they can detect. However, the challenge, Levy said, is what doctors can’t see.
“Stage IIB through Stage IV describes patients whose melanoma has characteristics that put them at higher risk of recurrence,” she detailed.
“At Stage IIB and IIC, the melanoma may still be localized to the skin, but features such as the depth of the tumor or ulceration make it higher risk. Stage III generally means melanoma has spread regionally, such as to nearby lymph nodes. Stage IV means it has spread to distant parts of the body — although in the patients in this trial, that disease had been completely removed surgically.”
— Joan Levy, PhD
“So these patients may have no detectable cancer after surgery, but they can still have microscopic melanoma cells remaining somewhere in the body,” Levy continued. “Those cells can eventually begin growing again. That’s why preventing recurrence is such an important goal. We don’t want to wait for melanoma to come back before treating it if we can safely intervene earlier.”
Every cancer has mutations in its DNA, Michael B. Atkins, MD, FAIO, FASCO, deputy director of the Georgetown Lombardi Comprehensive Cancer Center at Georgetown University, and board member of the Melanoma Research Foundation, explained to MNT, and melanoma is known to have a high number of these mutations due to damage from ultraviolet irradiation.
“Many of these mutations lead to abnormal proteins which can be recognized as foreign by the immune system. In order to escape immune recognition and destruction, cancers express proteins which disable the immune response. Pembrolizumab can block this disabling function (by) enabling the immune system to once again recognize and kill the tumors. After the tumor is resected, there are often insufficient immune cells around that can recognize the tumor as foreign.”
— Michael B. Atkins, MD, FAIO, FASCO
“Moderna has addressed this problem by taking a piece of resected melanoma, identifying the most likely DNA mutations to be recognized by the immune system, and creating a personalized mRNA vaccine that encompasses these mutations,” Atkins explained.
“In simple terms, this therapy is like creating a custom-built ‘wanted poster’ for your immune system to hunt down your specific cancer,” added Andrew Pecora, MD, co-division chief of the Skin and Sarcoma Service at the John Theurer Cancer Center at Hackensack University Medical Center in New Jersey. “After your tumor is surgically removed, scientists analyze its DNA to find unique mutations, or ‘flags,’ that are only present on your cancer cells.”
How mRNA vaccines work
“Using mRNA technology — the same kind used in some COVID vaccines — they create a personalized vaccine containing the instructions for your body to produce these harmless cancer flags. Once injected, your cells make these flags, and your immune system recognizes them as dangerous, training a highly specialized army of cells to seek and destroy anything that carries them.”
— Andrew Pecora, MD
“This newly trained immune army then acts as a long-term surveillance force, patrolling your body to eliminate any microscopic cancer cells that may have been left behind after surgery, thereby preventing the melanoma from ever coming back,” Pecora added.
According to Moderna and Merck, after a 5-year follow-up, study participants given the new therapy experienced a 49% reduction in the risk of recurrence or death, and a 59% lower risk of distant metastasis or death, compared with those receiving Keytruda alone.
Kim Margolin, MD, medical oncologist and medical director of The Borstein Family Foundation Melanoma Program at Providence Saint John’s Cancer Institute in Santa Monica, CA, told MNT that doctors already have effective adjuvant treatments that can reduce the risk of recurrence in patients with high risk melanoma, including immune checkpoint inhibitors such as pembrolizumab and nivolumab.
However, Margolin said, these therapies don’t eliminate the risk of recurrence for everyone, and some patients will still develop metastatic melanoma.
“We also have increasingly effective treatments for melanoma that has recurred or metastasized, but preventing recurrence remains an important therapeutic goal. The ideal strategy would identify and eliminate microscopic residual disease before it has an opportunity to grow and spread.”
— Kim Margolin, MD
“Therefore, the question is not whether we have effective treatments today, but whether we can improve upon them and identify which patients are most likely to benefit from additional or alternative approaches,” Margolin said.
Hilary Gomolin, MD, a medical oncologist and hematologist at the Eugene M. & Christine E. Lynn Cancer Institute, part of Baptist Health South Florida, agreed: “Currently, we have excellent options for treatment of high risk melanomas that have been resected with a number of different immunotherapy drugs that have shown improvement in disease-free survival. There is always the need to move science forward and improve outcomes for our patients.”
All experts agree that there are still questions and research to be done to continue evaluating this new potential therapy.
For instance, Christina M. Annunziata, MD, PhD, senior vice president, extramural discovery for the American Cancer Society, said that she would like to see the detailed results of the clinical trial, especially the length of the follow-up period, and to see the patients followed long-term to understand how durable the effect will be.
“From a safety perspective, the report indicates that the side effects were similar to Keytruda alone,” Annunziata told MNT. “For the patients who did not benefit from the vaccine, it would be interesting to sequence the cells in the relapsed cancer to see whether the mutational profile had changed.”
Shirin Bajaj, MD, a board certified dermatologist and Mohs micrographic surgeon starting at Mount Sinai in September, said she would also like to see the practical realities of this treatment option.
“Making a personalized vaccine currently takes on the order of six weeks from when a patient’s tumor and blood samples reach the central lab (the company’s stated turnaround target), though independent estimates run longer, roughly two to four months — so manufacturing turnaround, cost, insurance coverage, and equitable access will all matter a great deal for real-world use.”
— Shirin Bajaj, MD
The bottom line, she added, is this is one of the most promising advances in both melanoma care and personalized oncologic care in years.
“And a positive phase 3 result is a major step, but it’s not yet standard treatment,” Bajaj continued. “The study is still ongoing, and the detailed, longer-term data will tell us just how big a difference it truly makes.”
