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Second-Generation Vaccine for Melanoma Under Study: Did Men and Women Benefit Equally?

By: Joshua D. Madera, MD
Posted: Tuesday, April 30, 2024

Efforts to improve management strategies for patients with high-risk melanoma have led to the development of a second-generation vaccine that stimulates an immune response via helper T cells and natural killer cells, according to a study published in Nature Communications. The observed clinical benefits were significantly pronounced in male patients compared with female patients, explained Craig L. Slingluff, Jr, MD, of the University of Virginia Cancer Center, Charlottesville, and colleagues.

“The differences in benefit based on age and biological sex highlight the need to understand reasons for those differences, so we can provide the same benefit for all patients,” commented Dr. Slingluff in a University of Virginia press release. “Combination of the second-generation vaccine with other immune therapies may further increase the benefit for patients.”

From 2005 to 2008, a total of 167 patients were recruited from the Mel44 clinical trial. Patients were randomly assigned to one of four treatment groups, depending on the vaccine they were administered—12 class I MHC-restricted peptides (12MP) with nonspecific help (tet) or melanoma-specific help (6MHP)—and the administration of a single dose of cyclophosphamide. If the patient was assigned to receive cyclophosphamide, it was administered 5 days before the first vaccination. A total of 11 vaccinations were delivered over 1 year. Patients also attended regular follow-up to monitor clinical outcomes.

The study authors reported a prolonged, durable overall survival in patients who received the 12MP plus 6MHP vaccine compared with the 12MP plus tet. These clinical benefits were disproportionately observed in men compared with women. In addition, no overall benefit of cyclophosphamide pretreatment was observed. However, patients pretreated with cyclophosphamide who received the 12MP plus 6MHP vaccination series demonstrated the best clinical outcomes, suggesting a favorable interaction between cyclophosphamide and 6MHP.

Disclosure: For full disclosures of the study authors, visit nature.com.


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