Helgadottir, HildurGhiorzo, Paolavan Doorn, RemcoPuig i Sardà, SusanaLevin, MaxKefford, RichardLauss, MartinQueirolo, PaolaPastorino, LorenzaKapiteijn, EllenPotrony Mateu, MíriamCarrera Álvarez, CristinaOlsson, HåkanHöiom, VeronicaJönsson, Göran2021-01-082021-01-0820200022-2593https://hdl.handle.net/2445/173023Background: Inherited CDKN2A mutation is a strong risk factor for cutaneous melanoma. Moreover, carriers have been found to have poor melanoma-specific survival. In this study, responses to novel immunotherapy agents in CDKN2A mutation carriers with metastatic melanoma were evaluated. Methods: CDKN2A mutation carriers that have developed metastatic melanoma and undergone immunotherapy treatments were identified among carriers enrolled in follow-up studies for familial melanoma. The carriers' responses were compared with responses reported in phase III clinical trials for CTLA-4 and PD-1 inhibitors. From publicly available data sets, melanomas with somatic CDKN2A mutation were analysed for association with tumour mutational load. Results: Eleven of 19 carriers (58%) responded to the therapy, a significantly higher frequency than observed in clinical trials (p=0.03, binomial test against an expected rate of 37%). Further, 6 of the 19 carriers (32%) had complete response, a significantly higher frequency than observed in clinical trials (p=0.01, binomial test against an expected rate of 7%). In 118 melanomas with somatic CDKN2A mutations, significantly higher total numbers of mutations were observed compared with 761 melanomas without CDKN2A mutation (Wilcoxon test, p<0.001). Conclusion: Patients with CDKN2A mutated melanoma may have improved immunotherapy responses due to increased tumour mutational load, resulting in more neoantigens and stronger antitumorous immune responses.6 p.application/pdfengcc by-nc (c) Helgadottir et al., 2020http://creativecommons.org/licenses/by-nc/3.0/esMelanomaMetàstasiImmunoteràpiaMelanomaMetastasisImmunotheraphyinfo:eu-repo/semantics/article6884632021-01-08info:eu-repo/semantics/openAccess30291219