Men With Melanoma Who Receive Enhanced Vaccine Experience Improvements in Overall Survival

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A second-generation melanoma vaccine currently in development improves long-term survival in patients with melanoma compared with the first-generation vaccine, according to study authors who published their findings in Nature Communications. In addition, the vaccine demonstrated stronger efficacy in male patients than in female patients.¹

The study authors noted that it is unclear why the vaccine was more effective in men, however, they noted that biologic sex is showing to be an important factor in the outcomes of patients with melanoma, particularly with immune therapies. The vaccine was enhanced by the simultaneous stimulation of immune cells—helper T cells—to recognize melanoma proteins while also stimulating killer T cells against melanoma. This induces immune responses against human melanoma cells. This method, according to the authors, improved both patient survival and prevents reoccurrences of the cancer.¹

“These findings support the promise of this second-generation melanoma vaccine for prolonging survival of patients after surgery for high-risk melanoma,” said Craig L Slingluff, MD, surgical oncologist and translational immunologist at UVA Health and the University of Virginia School of Medicine, in a press release. “We hope that we can make this available to patients in addition to other effective immune therapies so that they may have even greater benefit than either treatment alone.”¹

According to the authors, the vaccine targets a form of skin cancer that kills thousands of Americans every year. When developing a more effective version of the vaccine, 2 different approaches were made to stimulate both CD4+ helper T cells and CD8+ killer T cells in patients with high-risk melanoma. In this multicenter phase 2 trial, patients were randomly assigned to receive 1 of 2 vaccine preparation that consisted of either 12 melanoma peptides or 6 melanoma helper peptides that would stimulate their helper T cells.^1,2

The findings demonstrated that 15 years after the final participant was enrolled in the trial, overall survival (OS) rates were positive for both vaccines; however, OS was better for those who received the second-generation vaccine. Particularly, younger men with earlier-stage melanoma appeared to benefit the most from this vaccine. In the study, sex was not shown to be a significant covariate for OS in the analysis for the 2.5-year follow-up landmark, but the hazard ratio for OS by vaccine regimen was more favorable for male patients (0.49; 95% CI 0.23–1.04) than for female patients (0.62; 95% CI 0.20–1.94). Further, OS estimates at 10 years were 0.84 ± 0.05 (SE) and 0.72 ± 0.11 for males and females, respectively. The authors noted that this finding suggests the importance that age and sex may play when determining immune therapy outcomes and treatments for patients with melanoma.^1,2

“We were very excited by these findings and for the promise to improve survival with these vaccines. Combination of the second-generation vaccine with other immune therapies may further increase the benefit for patients,” said Slingluff in the press release. “The differences in benefit based on age and biologic sex highlight the need to understand reasons for those differences so that we can provide the same benefit for all patients. We are excited to build on these exciting findings.”¹

References

1. University of Virginia Health System. Enhanced melanoma vaccine offers improved survival for men. News releases. March 29, 2024. Accessed April 1, 2024. https://www.eurekalert.org/news-releases/1039351

2. Ninmer, EK, Zhu, H, Chianese-Bullock, KA, et al. Multipeptide vaccines for melanoma in the adjuvant setting: long-term survival outcomes and post-hoc analysis of a randomized phase II trial. Nat Commun 15, 2570 (2024). doi:10.1038/s41467-024-46877-6