Journal of Clinical and Aesthetic Dermatology • Hot Topics in Melanoma July 2025 • NEWS & TRENDS

NEW DATA AT ASCO 2025 AFFIRMS DECISIONDX®-MELANOMA’S ABILITY TO IMPROVE UPON STAGING-BASED RISK STRATIFICATION AND PREDICT SURVIVAL OUTCOMES

Use of DecisionDx-Melanoma, a 31-gene expression profile (GEP) test, was associated with a 32-percent reduction in mortality risk compared to untested patients in an expanded, real-world cohort of more than 13,500 patients with melanoma. These findings presented at the 2025 American Society of Clinical Oncology (ASCO) Annual meeting provided precise risk predictions based on patients’ unique tumor biology and improved upon the population-based risk assessment provided by American Joint Committee on Cancer (AJCC) staging.

Recent research demonstrated the effectiveness of tumor-infiltrating lymphocytes (TILs) for the treatment of melanoma in treating patients who have progressed after treatment with checkpoint inhibitors. The recent FDA-approval of TILs stems from a Phase 2 clinical trial for advanced melanoma that demonstrated a 31 percent objective response rate in this group of patients. This led to a follow-up Phase 3 trial that not only improved objective response rates but extended the median overall survival and provided sustained responses for prolonged periods.

HIGH-FIBER DIET COULD IMPROVE RESPONSE TO IMMUNOTHERAPY FOR PATIENTS WITH MELANOMA

Findings presented at the 2025 ASCO Annual Meeting demonstrated a high-fiber diet can increase the response to immunotherapy for patients with melanoma compared with patients with a healthy control diet. In a randomized Phase II trial, participants who consumed up to 50g of fiber every day had a 50-percent higher objective response rate than those who consumed 20g of fiber per day. This same high-fiber diet is recommended for secondary cancer prevention and cardiometabolic health, demonstrating its ability to improve outcomes in patients receiving immunotherapy.

A large cohort study demonstrated increased melanoma risk in by 3.2 percent (hazard ratio [HR]: 1.032; p=0.005) in individuals with an additional blistering sunburn before the age of 15 years. The association was consistent regardless of eye color, hair color, ultraviolet (UV) radiation exposure, or time outdoors. The results showed a higher melanoma risk in individuals with brown/hazel eye color, dark hair color, and light skin complexion. Additionally, ambient UV exposure and individual sun sensitivity traits did not impact the association between the number of blistering sunburns and risk of melanoma.

A VIRUS-BASED VACCINE COMBINED WITH IL-12 GENE THERAPY ERADICATES AGGRESSIVE MELANOMA

A recent study assessed the antitumor efficacy in a bacteriophage-based vaccine strategy as a standalone therapy and in combination with gene electrotransfer (GET) of interleukin (IL)-12 plasmids. The response to the vaccine was characterized by histological and immunohistochemical analyses of tumor tissue. The researchers found that engineered bacteriophage therapy significantly delayed tumor growth, and GET IL-12 therapy contributed to the therapeutic effect of engineered bacteriophages and increased tumor growth delay. Immunotherapy and an increased tumor death was discovered when utilizing both bacteriophage monotherapy and, especially in combination with GET IL-12 therapy.

Recent research demonstrated that in many cases, immunotherapy works remarkably better than surgery as a first course of action in treating advanced melanoma. In two large, randomized trials, neoadjuvant immunotherapy improved outcomes compared to adjuvant immunotherapy, with an approximately 50-percent improvement in event-free survival in patients with Stage III and IV melanoma. The research was based on preliminary lab work demonstrating the ability of immunotherapy to increase effectiveness before surgery by activating immune T cells associated with tumor generating memory T cells, which have the ability to remember the tumor.

The current impact of pregnancy on patients with melanoma remains unclear, but researchers suggest that any observed changes in melanocytic nevi during pregnancy should be considered suspicious unless proven otherwise. Alterations in the size and pigmentation of nevi during pregnancy are commonly reported, though their frequency and significance remains variable. The most accepted explanation for changes in the skin during pregnancy in patients with melanoma is that there is a mechanical stretching of the skin that occurs during pregnancy. Hormonal factors have also been proposed as a cause, but the supporting evidence remains inconclusive.

RP1 YIELDS RESPONSES IN DEEP/ VISCERAL LESIONS AND ACROSS INJECTED/NONINJECTED LESIONS IN ADVANCED PD-1–REFRACTORY MELANOMA

Responses to immunotherapy utilizing RP1 (vusolimogene oderparepvec) in combination with nivolumab showed efficacy in patients with advanced melanoma, with higher response rates in deep and visceral injections compared to superficial injections alone. Deep and visceral injections were safe and led to numerically higher response rates compared with superficial injections alone, according to data from an analysis of the Phase II IGNYTE trial presented at the 2025 ASCO Annual Meeting.

INHERITED GENETIC DIFFERENCES MIGHT PREDICT RESISTANCE TO IMMUNOTHERAPY IN METASTATIC MELANOMA

An investigation assessing mitochondrial haplogroups in DNA might have uncovered genetic differences to better predict responses to immune checkpoint inhibitors (ICIs) among patients with metastatic melanoma. Researchers evaluated blood samples from 1,225 patients participating in the Phase III CheckMate-067 trial, which examined the frontline use of ICIs to treat metastatic melanoma. The research discovered inherited genetic differences in mitochondrial DNA that predicted resistance to ICIs. Patients with mitochondrial haplogroup T were 3.46 times less likely to respond to treatment with nivolumab monotherapy or nivolumab in combination with ipilimumab compared with patients who had different mitochondrial haplogroups. Validation analysis, which included 675 patients, confirmed the association between haplogroup T and treatment resistance.

RESEARCH BITE—IBI363 showed breakthrough efficacy in patients with heavily-treated melanoma subtypes

Research presented at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting showed a breakthrough in efficacy from IBI363, a first-in-class programmed cell death-1 (PD-1)/ interleukin (IL)-2^α^-bias bispecific antibody fusion protein, in heavily-treated melanoma subtypes (acral and mucosal). The results demonstrated a strong tumor response to long-term survival benefits that supports the drug’s novel mechanism of action and shows its potential for a broader clinical development in areas of immunotherapy where treatment options are limited.

RESEARCH BITE—High UV exposure tied to elevated melanoma risk in large NIH-AARP study

A recent study that assessed erythemal ultraviolet (UV) radiation showed there could be a relationship between UV exposure and invasive melanoma. A large cohort of over 490,000 participants between the ages of 50 and 71 years were included for analysis. Researchers assessed participants’ UV exposure based on varying quartiles, from less than 180J/m2 to over 236J/m². Researchers reported that patients with over 236J/m² of UV exposure had a 32-percent increased risk of invasive melanoma and 37-percent increased risk of melanoma in situ.