Identification of patients at high risk for relapse using the Merlin Assay (CP-GEP) in an independent cohort of 451 patients (pts) with stage I/II melanoma who did not undergo sentinel lymph node biopsy.

9574 Background: Sentinel lymph node biopsy (SLNB) is the gold standard for nodal assessment in staging cutaneous melanoma (CM) according to AJCC v8 guideline. 80-85% of pts are negative for nodal metastasis, but most pts who relapse or die from melanoma are initially diagnosed as ‘low risk’ early-stage. Previously we showed that the clinicopathological-gene expression profiling (CP-GEP) model is able to stratify SLNB negative pts for their risk of recurrence (1). Later we showed in a small cohort (n=80) that CP-GEP also has the potential to stratify pts who did not undergo SLNB in low and high-risk of recurrence (2). Here we investigate CP-GEP ability to stratify pts who did not undergo SLNB for their risk of recurrence in an expanded cohort. Methods: We analysedformalin-fixed paraffin-embedded primary tumor samples of 451 pts with stage I/II CM diagnosed between 2000-2017, included in the Central Malignant Melanoma Registry, who did not receive SLNB. Study hypothesis and protocol were prospectively formulated. Tumors were analyzed blinded to clinical outcome. The CP-GEP model used combines the expression of 8 genes ( SERPINE2, GDF15, ITGB3, CXCL8, LOXL4, TGFBR1, PLAT and MLANA) by quantitative reverse transcription polymerase chain reaction with age and Breslow thickness to obtain a binary output: CP-GEP Low- or High-Risk. Relapse-free survival (RFS), distant metastasis free survival (DMFS) and Melanoma Specific Survival (MSS) were evaluated using Kaplan-Meier curves. Results: We included 451 pts (stage IA-IIC). 40% were females, median age was 63-year-old, median Breslow thickness was 0.5 mm, and the majority were not ulcerated (96%). An interim analysis was performed on samples from 159 pts and showed the following survival: 5-year RFS 85.8%; DMFS 94.1; MSS 95.7%. The median follow-up time of 57 months (RFS). CP-GEP identified 149 pts as Low-Risk and 10 pts as High-Risk. The 5-year RFS rate was 90.5% and 0% (HR 23.85; p < 0.001), 5-year DMFS was 97.2% and 27% (HR 43.14; p < 0.001), respectively for CP-GEP Low-Risk and High-Risk pts. The 5-year MSS was 99.1% for Low-Risk pts and 25.7% for High-Risk patients (HR 112.96; p < 0.001), capturing 4 out of 5 melanoma specific deaths in the CP-GEP High-Risk group. The final survival analysis of the whole cohort will be presented at the congress. Conclusions: This study shows that CP-GEP has the potential to stratify pts with early-stage melanoma who did not undergo SLNB based on their risk of recurrence. Pts with CP-GEP Low-Risk have a good long-term survival. Contrary, pts with CP-GEP High-Risk have a high risk of recurrence. CP-GEP may have the potential to stratify pts beyond SLNB. 1. Amaral et al, ASCO 2022. 2. Amaral et al, EJC 2023.