2017 S46 Lebanese Medical Journal • Mars 2019 • Vol 67 (Abstracts) QuANtItAtIVE MONItORING OF CIRCuLAtING tuMOR DNA PREDICtS RESPONSE OF CutANEOuS MEtAStAtIC MELANOMA tO ANtI-PD1 IMMuNOthERAPY http://www.lebanesemedicaljournal.org/articles/67-A/doc24.pdf 1,2 Herbreteau G, 1,2 Vallée A, 2 Knol A, 1,2 Théoleyre S, 2,3,4 Quéreux G, 2,4 Varey E 2,3,4 Khammari A, 2,3,4 Dréno B, 1,2 Denis M Introduction • Anti-PD1 immunotherapies are drastically changing the current standard of care of metastatic cutaneous melanoma. however, about 60% of the treated patients do not respond to anti-PD1, and atypical radiological responses delays the detection of primary resistances. the objective of this study was to determine whether the quantitative monitor- ing of circulating tumor DNA (ctDNA) could early predict the tumor response to anti-PD1. Material and Methods • Fifty-two patients treated with anti-PD1 at Nantes University hospital for metastatic cutaneous melanoma were selected on their BRAF and NRAS muta- tional status. Plasmas were collected at the initiation of the treatment, at 2 and 4 weeks of treatment, and then every 4 weeks until the progression. Circulating DNA was extracted from 2 ml of plasma. to evaluate specifically the concentration of tumor circulating DNA (ctDNA) fraction, the somatic alterations detected in tissue were quantified by digital PCR (dPCR). Results • ctDNA was detectable at initiation of treatment for 22/52 patients (42%). Absence of detectable ctDNA prior to the treatment was associated with a favorable prognosis in overall survival. During the follow-up, we defined a biological response (bR) as a signifi- cant decrease in the amount of ctDNA relative to the baseline level (considering the preci- sion of dPCR measurement) and biological progression (bP) as a significant increase in the amount of ctDNA relative to its nadir. the absence of biological response after 2 weeks of treatment was associated with a lack of clinical benefit of anti-PD1, with a response rate of 0% and PFS all inferior to 120 days (n = 10). In contrast the detection of a bR at week 2 was associated with a response rate of 50% (n = 12). For these patients, detection of bP at 4, 8 or 16 weeks of treatment was 100% predictive of a subsequent progressive disease (n = 6), on average 75 days prior its radiological detection. All patients with a persistent bR beyond the 16th week (n = 6) did not experience any progressive disease and continued sustained responses, with PFS of at least 306 to 755 days (ongoing). Conclusion • the quantitative monitoring of ctDNA, taking into account the measurement precision of dPCR, allows a specific, sensitive and early detection of non-responsive patients to anti-PD1. we propose a simple and non-invasive test to improve the management and follow-up of patients treated with anti-PD1, for whom predictive markers are still limited. Keywords: metastatic melanoma; immunotherapy; tumor DNA 1 Laboratoire de Biochimie et Plateforme de génétique moléculaire des cancers CHU de Nantes Nantes. France 2 Centre de Recherche en Cancérologie et Immunologie INSERM U1232 Nantes. France 3 Service de Dermatologie CHU de Nantes Nantes. France 4 Centre d’Investigation Clinique INSERM CIC1413 CHU de Nantes Nantes. France