Autoimmune genetic variants as germline biomarkers of response in melanoma immunotherapy treatment.

3079Background: Immune checkpoint inhibition (ICI) has improved clinical outcomes for metastatic melanoma patients. However, ~ 60% of patients do not respond to ICI and 65-80% experience immune-related adverse events (irAEs). Currently, the personalized biomarkers predicting ICI efficacy or toxicity are limited. Given the link between immunotherapy, irAEs and autoimmunity, we investigated if the baseline genetic susceptibility to multiple autoimmune diseases can modulate clinical efficacy of ICI. Methods: By performing a comprehensive search of autoimmune genome wide association studies, we identified 25 SNPs, each associated with at least 3 autoimmune diseases. Using the Agena MassArray, we genotyped 25 SNPs in 389 Caucasian metastatic melanoma patients receiving ICI treatment (N = 214 anti-CTLA4, N = 175 anti-PD1) at one of our collaborative centers. Multivariate logistic regression adjusting for age at treatment and gender was used to test for association of germline variants with ICI efficacy. Results...