TY - JOUR T1 - Efficacy of novel immunotherapy regimens in patients with metastatic melanoma with germline <em>CDKN2A</em> mutations JF - Journal of Medical Genetics JO - J Med Genet SP - 316 LP - 321 DO - 10.1136/jmedgenet-2018-105610 VL - 57 IS - 5 AU - Hildur Helgadottir AU - Paola Ghiorzo AU - Remco van Doorn AU - Susana Puig AU - Max Levin AU - Richard Kefford AU - Martin Lauss AU - Paola Queirolo AU - Lorenza Pastorino AU - Ellen Kapiteijn AU - Miriam Potrony AU - Cristina Carrera AU - Håkan Olsson AU - Veronica Höiom AU - Göran Jönsson Y1 - 2020/05/01 UR - http://jmg.bmj.com/content/57/5/316.abstract N2 - Background 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&lt;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. ER -