Twenty‐year survival outcomes after multipeptide vaccination for resected high‐risk melanoma: A post‐hoc analysis of a randomized clinical trial

• Published in: International journal of cancer Vol. 157; no. 9; pp. 1912 - 1923
• Main Authors: Ninmer, Emily K., Zhu, Hong, Chianese‐Bullock, Kimberly A., Slingluff, Craig L.
• Format: Journal Article
• Language: English
• Published: Hoboken, USA John Wiley & Sons, Inc 01.11.2025; Wiley Subscription Services, Inc
• Subjects: Adult; Aged; Cancer Vaccines - administration & dosage; Cancer Vaccines - immunology; Cancer Vaccines - therapeutic use; CD8 antigen; CD8-Positive T-Lymphocytes - immunology; Clinical outcomes; Clinical trials; Female; Follow-Up Studies; Humans; Immune response; Immunogenicity; Immunotherapy; Lymphocytes T; Major histocompatibility complex; Male; Melanoma; Melanoma - immunology; Melanoma - mortality; Melanoma - pathology; Melanoma - therapy; Middle Aged; peptide vaccine; Peptides; Response rates; shared antigens; Skin Neoplasms - immunology; Skin Neoplasms - mortality; Skin Neoplasms - pathology; Skin Neoplasms - therapy; Treatment Outcome; Vaccination; Vaccines; Vaccines, Subunit - administration & dosage; Vaccines, Subunit - immunology; melanoma; peptide vaccine; shared antigens; immunotherapy
• ISSN: 0020-7136; 1097-0215; 1097-0215
• DOI: 10.1002/ijc.70006

In this post‐hoc analysis, we report long‐term clinical outcomes of a randomized phase II clinical trial (Mel39, NCT00938223) that tested the immunogenicity of two multipeptide vaccines designed to stimulate CD8+ T cells in patients with high‐risk melanoma. Fifty‐one participants with resected stage IIB‐IV melanoma randomized to vaccination with 4 or 12 melanoma peptides were followed for clinical outcomes. Overall survival (OS) and recurrence‐free survival (RFS) by vaccine arm, immune response, age, sex, and stage were evaluated. Median follow‐up was 16.1 years for all participants and 21.2 years for living participants. OS rates (95% CI) for both vaccine arms were 65% (51–78%) and 49% (35–63%) at 10 and 20 years, respectively, favoring vaccination with 12 melanoma peptides (HR 0.64, 95% CI: 0.29–1.40; p = .26) with a promising difference given the study sample size. Females had significantly improved RFS compared to males after either vaccine regimen, independent of peripheral immune response to the vaccine (HR 0.42, 95% CI: 0.19–0.91; p = .03). Overall, clinical efficacy was not significantly improved with more class I major histocompatibility complex (MHC)‐restricted peptides to the vaccine despite more favorable peripheral immune response rates on treatment. Females had durable RFS after vaccination that was not explained by sex‐associated differences in peripheral CD8+ T cell response rates during treatment. Further work to identify clinically meaningful vaccine‐induced T cell responses and how to optimize vaccines to elicit these responses is needed, including investigation into the influence of host factors on the response to immunotherapy. What's new? While melanoma vaccines have shown therapeutic promise, predicting their clinical benefits is challenged by factors such as delayed response to immunotherapy and scarcity of biomarkers. Here, the authors examined the long‐term efficacy of vaccination with either 4 or 12 class I MHC‐restricted peptides in high‐risk melanoma. Long‐term survival following treatment with either vaccine regimen was favorable, with the addition of more MHC class I‐restricted peptides exhibiting no clear clinical benefit in melanoma patients. Durable RFS was observed among vaccine‐treated females, independent of peripheral CD8+ T cell responses, underscoring a need to better understand interactions between host factors and immunotherapy.