KEY TAKEAWAYS
- The phase 2 study aimed to investigate the long-term impact of vaccination with 12MP compared to 4MP.
- Researchers noticed a favorable impact of the 12MP vaccine on OS for males and RFS for females.
Cancer vaccines utilizing Class I MHC-presented peptides have demonstrated potent CD8+ T cell responses. Shared antigens like melanocyte differentiation proteins (MDP) and cancer-testis antigens (CTA) express commonly in melanoma cells, yet immune evasion after vaccination with limited antigens poses challenges.
The Mel39 vaccine trial investigated the safety and immunological effects of a 12 Class I MHC-restricted melanoma peptides (12MP) from MDP and CTA, compared to a four-peptide vaccine (4MP) from MDP. Despite competition for MHC binding, 12MP induced a broader and more robust immune response than 4MP, correlating with clinical outcomes.
Emily K Ninmer and her team aimed to evaluate long-term clinical outcomes, hypothesizing improved overall survival (OS) and recurrence-free survival (RFS) with 12MP vaccination. The objective was to analyze the long-term clinical outcomes, expecting favorable results with the 12MP vaccine.
The study performed the Mel39 trial (NCT00938223) with 51 eligible participants having resected stage IIB-IV melanoma. These individuals were randomized to receive vaccination with either 12MP or 4MP along with a tetanus helper peptide. Long-term follow-up focused on assessing survival and disease recurrence. To evaluate clinical outcomes, differences in OS and RFS were analyzed using Kaplan-Meier survival estimates. Exploratory subgroup analyses based on patient sex were conducted, and hazard ratios (HR) were reported to provide insights into the observed differences.
In this analysis with a median follow-up of 11.1 years, OS at 12 years was approximately 60% for both vaccines, displaying a weak trend favoring the 12 Class I MHC-restricted melanoma peptide (12MP) vaccine (HR 0.63, 95% CI 0.29 to 1.39). RFS curves were similar between the two vaccine groups. Exploratory analysis by patient sex indicated trends favoring 12MP for OS in males (HR 0.51, 95% CI 0.18 to 1.46;) and for RFS in females (HR 0.43, 95% CI 0.15 to 1.22). Overall, females demonstrated significantly improved RFS compared to males, irrespective of the vaccine regimen (HR 0.44, 95% CI: 0.21 to 0.90), manifesting an approximate 30 % point difference in RFS at 5 and 10 years.
The study provided evidence that, following vaccination with multipeptide vaccines, a majority of patients exhibit long-term survival. Although the addition of more peptides did not yield a significant extension in OS or RFS, it is noted that the trial was not powered for clinical outcome assessment.
Noteworthy trends indicated a favorable impact of the 12MP vaccine on OS for males and RFS for females. Furthermore, females consistently demonstrated significantly improved RFS compared to males, irrespective of the vaccine received. These findings underscore the necessity for comprehensive analysis of the influence of patient sex on the clinical outcomes of cancer vaccines.
The study is sponsored by Craig L Slingluff
Source: https://jitc.bmj.com/content/11/Suppl_1/A714
Clinical Trial: https://clinicaltrials.gov/study/NCT00938223
Ninmer E K. and Slingluff C L. (2023).”Long-term outcomes of a randomized trial of two multipeptide melanoma vaccines (Mel39) suggests outcome differences based on participant sex”. Presented at SITC 2023 (Abstract 626).
