Background: A novel immune checkpoint inhibitor, nivolumab, have contributed higher efficacy for patients with metastatic melanoma. Although clinical effects by this agent is usually evaluated by radiologic examinations, this cannot be performed frequently. Circulating tumor DNA (ctDNA) is expected as a realtime biomarker for evaluating tumor burden. Aim: We assessed whether ctDNA in melanoma patients treated with nivolumab could be a significant marker superior to serum LDH levels and radiologic images. Methods: 5 patients with metastatic melanoma were examined. The profiles of genome status were as follows, BRAFV600E; 3, BRAFV600K; one and NRASQ61K; one. Levels of BRAF and NRAS ctDNA were determined using droplet digital PCR. Results: In 4 of 5 patients, ctDNA levels were correlated with and preceded the radiologic changes. Moreover in all 5 patients, ctDNA levels changed within 2-4 weeks, which was prior to the first radiologic examination after nivolumab initiation. In 3 of 5 patients, LDH levels did not corresponded to the tumor dynamics. Conclusion: ctDNA could be a significant indicator expecting clinical response to nivolumab treatment in metastatic melanoma patients.

Circulating tumor DNA for monitoring treatment response to anti-PD-1 immunotherapy in melanoma patients