1. 18-month recurrence-free survival was significantly greater in the combination therapy group compared to pembrolizumab alone.

2. There were no treatment-related grade 4-5 adverse events or fatalities reported.

Evidence Rating Level: 1 (Excellent)

Study Rundown: Checkpoint inhibitors are now commonly used as adjuvant therapy for resected melanoma, yet recurrence remains a concern among many patients. mRNA-4157 (V940) is a novel individualized mRNA-based neoantigen therapy which may improve survival in high-risk melanoma patients, although further research is needed. This randomized controlled trial aimed to evaluate the impact of adjuvant mRNA-4157 plus pembrolizumab on recurrence-free survival. The primary outcome of this study was recurrence-free survival, while key secondary outcome was distant metastasis-free survival. According to study results, the combination therapy significantly increased recurrence-free survival compared to pembrolizumab monotherapy. Although this study was well done, it was limited by a relatively small sample size and the open-label design, which may introduce biases.

Click to read the study in The Lancet

Relevant Reading: Perioperative Pembrolizumab for Early-Stage Non–Small-Cell Lung Cancer

In-depth [randomized-controlled trial]: Between July 18, 2019, and Sept 30, 2021, 224 patients were assessed for eligibility across the USA and Australia. Included were patients ≥ 18 years of age with resectable high-risk cutaneous melanoma (stage IIIB–IV). Altogether, 157 patients (107 in mRNA-4157 plus pembrolizumab and 50 in pembrolizumab alone) were included in the final analysis. The primary outcome of recurrence-free survival was increased in the combination therapy group compared to monotherapy (hazard ratio [HR] for recurrence or death 0.561, 95% confidence interval [CI] 0.309-1.017, p=0.053). Similarly, the 18-month recurrence-free survival was 79% (95% CI 69.0-85.6) for combination therapy versus 62% (95% CI 46.9-74.3) for pembrolizumab alone. Findings from this study suggest that adjuvant mRNA-4157 plus pembrolizumab may improve recurrence-free survival in patients with resected high-risk melanoma.

Image: PD

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