Efficacy of novel immunotherapy regimens in patients with metastatic melanoma with germline CDKN2A mutations.
J Med Genet
; 57(5): 316-321, 2020 05.
Article
en En
| MEDLINE
| ID: mdl-30291219
ABSTRACT
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.Palabras clave
Texto completo:
1
Base de datos:
MEDLINE
Asunto principal:
Inhibidor p16 de la Quinasa Dependiente de Ciclina
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Antígeno CTLA-4
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Receptor de Muerte Celular Programada 1
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Melanoma
Tipo de estudio:
Observational_studies
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Prognostic_studies
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Risk_factors_studies
Idioma:
En
Revista:
J Med Genet
Año:
2020
Tipo del documento:
Article