Comparative efficacy of serum lactate dehydrogenase levels versus circulating cell-free microRNAs in monitoring response to checkpoint inhibitor immunotherapy treatment in metastatic melanoma patients

This study compares the efficiency of cfmiR signatures versus sLDH levels in assessing and monitoring melanoma patients' responses during the course of their CII treatment. The cfmiRs were evaluated using a next generation HTG EdgeSeq microRNA (miR) Whole Transcriptome Assay (WTA) in 161 serial bleed samples obtained during the course of the CII treatment from 48 stage III and IV melanoma patients. Initially, cfmiRs were profiled in pre- and post-treatment plasma samples of stage IV non-responsive melanoma patients and compared to normal donors’ plasma samples. A 9 cfmiR signature was identified in pre- and post-treatment samples that was associated with having no response to CII. These cfmiRs were then compared in pre- and post-treatment plasma samples from stage IV responsive melanoma patients. MiR-4745-3p, miR-615-3p, and miR-6511-3p showed potential predictive abilities in assessing CII response. In stage III melanoma patients, miRs found in pre-treatment plasma samples were associated with response to CII therapy. Our results showed that compared to elevated baseline LDH levels, cfmiRs were consistently more efficient in detecting melanoma patients undergoing CII therapy who will develop progressive disease. By using this minimally invasive assay, we identified a cfmiR signature that could assess responses and allow for potential real-time monitoring of patients receiving CII treatment.