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cc by-nc (c) Helgadottir et al., 2020
Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/173023

Efficacy of novel immunotherapy regimens in patients with metastatic melanoma with germline CDKN2A mutations

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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<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.

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HELGADOTTIR, Hildur, GHIORZO, Paola, VAN DOORN, Remco, PUIG I SARDÀ, Susana, LEVIN, Max, KEFFORD, Richard, LAUSS, Martin, QUEIROLO, Paola, PASTORINO, Lorenza, KAPITEIJN, Ellen, POTRONY MATEU, Míriam, CARRERA ÁLVAREZ, Cristina, OLSSON, Håkan, HÖIOM, Veronica, JÖNSSON, Göran. Efficacy of novel immunotherapy regimens in patients with metastatic melanoma with germline CDKN2A mutations. _Journal of Medical Genetics_. 2020. Vol. 57, núm. 5, pàgs. 316-321. [consulta: 20 de gener de 2026]. ISSN: 0022-2593. [Disponible a: https://hdl.handle.net/2445/173023]

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