Abstract 7626: Assessment of precision melanoma diagnostics: Circulating microrna expression to monitor late-stage treatment
Authors: Harris Teresa , Zaenker Pauline , McEvoy Ashleigh C. , Soyer H. Peter , Khattak Muhammad A. , Ziman Melanie , Millward Michael , Gray Elin S. , Stark Mitchell S. 
Published: March 2024

Abstract
Metastatic melanoma patients are commonly treated with targeted (e.g., BRAF/MEK inhibitors) and/or immune checkpoint therapies and treatment efficacy is then assessed with radiological scans. These scans are highly effective for the staging of the disease but in terms of follow-up, there are several limitations including the inability to detect minimal residual disease (MRD). Circulating biomarkers are a viable solution to overcome these limitations, and this study sought to investigate a panel of melanoma-specific microRNA (miRNA) biomarkers in stage IV patients undergoing therapy. This panel had previously been assessed in treatment naïve stage IV patients, with members of the MELmiR-7 panel able to detect an increase in tumor burden in 100% of cases, as well as the ability to define overall survival (OS) superior to serum lactate dehydrogenase (LDH) and S100B levels (delta log-likelihood = 11, p&lt; 0.001). In this multi-center longitudinal study, bloods were drawn from study participants from 2013-2015, with clinical follow-up until October 2018. The expression levels of the MELmiR-7 panel were assessed in serially collected serum (≥3 timepoints; ≥2-month intervals) collected from a total of 23 melanoma patients, treated with BRAF/MEK inhibitors and/or anti-CTLA4 and/or anti-PD-1. The goal was to determine if the panel could predict treatment success/failure, as well as patient OS, if treated with the same therapy. All miRNA panel members were measured using a sensitive real-time PCR assay at each time point, but only miR-4731 gave stable expression over the course of the therapy, with other panel members fluctuating post treatment. The stability of miR-4731 expression over time indicated that this marker was not affected by treatment type, rather changes in its expression were reflective of disease progression/regression (as determined by radiological images), thus making it an ideal biomarker. Importantly, across the cohort of 23 patients, miR-4731 expression had the ability to predict treatment outcome (Complete Response/Stable Disease (n=12) vs Melanoma Death (n=11)) for patients at ≥2 months post therapy vs baseline, with a high degree of precision (Mann Whitney, 2-tailed; p=0.0004). Area under the curve analysis also found miR-4731 expression to be highly sensitive and specific (AUC=0.91; p=0.0009) at predicting overall survival (OS). Furthermore, in Kaplan-Meier survival analysis, participants with high serum expression (≥2 months post therapy vs baseline) of miR-4731, had poor OS (p=0.0045; 14-month median survival) as compared with low serum miRNA expression which was predictive of a positive prognosis. In sum, assessment of this miRNA marker during therapy would permit early on-treatment prediction of patient outcomes, independent of imaging, to either continue to treat with current regimen, or to switch treatment modalities.
Citation Format: Teresa Harris, Pauline Zaenker, Ashleigh C. McEvoy, H. Peter Soyer, Muhammad A. Khattak, Melanie Ziman, Michael Millward, Elin S. Gray, Mitchell S. Stark. Assessment of precision melanoma diagnostics: Circulating microrna expression to monitor late-stage treatment [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 7626.