The phase 2b KEYNOTE-942 RCT (n=157; 107 intismeran + pembrolizumab vs 50 pembrolizumab alone) demonstrated a sustained 49% reduction in recurrence or death risk at five years, with recurrence-free survival of 68.8% versus 49.1% and overall survival of 92.2% versus 71.3%. This randomized design provides higher-quality evidence than observational series, though the modest sample size and industry sponsorship (Merck/Moderna) warrant scrutiny for potential bias in endpoint selection. Unlike shorter-term reports, these data highlight durability against distant metastasis (59% risk reduction), addressing a gap in prior adjuvant melanoma trials where PD-1 inhibitors alone show waning benefit by year three. Connections to parallel mRNA efforts, such as the Moderna-MERCK mRNA-4157 phase 3 expansion (NCT05955261) and BioNTech's BNT111 melanoma program, suggest platform-level potential for neoantigen targeting in tumors with high mutational burden. Mainstream coverage often overlooks how T-cell priming via mRNA may overcome PD-1 resistance mechanisms that emerge in 40-60% of pembrolizumab monotherapy cases. Larger confirmatory phase 3 results will determine if this combination displaces current standards without added grade 3-4 toxicity.