Germline variants associated with toxicity to immune checkpoint blockade.
Groha S., Alaiwi SA., Xu W., Naranbhai V., Nassar AH., Bakouny Z., El Zarif T., Saliby RM., Wan G., Rajeh A., Adib E., Nuzzo PV., Schmidt AL., Labaki C., Ricciuti B., Alessi JV., Braun DA., Shukla SA., Keenan TE., Van Allen E., Awad MM., Manos M., Rahma O., Zubiri L., Villani A-C., Fairfax B., Hammer C., Khan Z., Reynolds K., Semenov Y., Schrag D., Kehl KL., Freedman ML., Choueiri TK., Gusev A.
Immune checkpoint inhibitors (ICIs) have yielded remarkable responses but often lead to immune-related adverse events (irAEs). Although germline causes for irAEs have been hypothesized, no individual variant associated with developing irAEs has been identified. We carried out a genome-wide association study of 1,751 patients on ICIs across 12 cancer types. We investigated two irAE phenotypes: (1) high-grade (3-5) and (2) all-grade events. We identified 3 genome-wide significant associations (P