Germline variants associated with toxicity to immune checkpoint blockade
Groha S, Alaiwi S, Xu W, Naranbhai V, Nassar A, Bakouny Z, El Zarif T, Saliby R, Wan G, Rajeh A, Adib E, Nuzzo P, Schmidt A, Labaki C, Ricciuti B, Alessi J, Braun D, Shukla S, Keenan T, Van Allen E, Awad M, Manos M, Rahma O, Zubiri L, Villani A, Fairfax B, Hammer C, Khan Z, Reynolds K, Semenov Y, Schrag D, Kehl K, Freedman M, Choueiri T, Gusev A. Germline variants associated with toxicity to immune checkpoint blockade. Nature Medicine 2022, 28: 2584-2591. PMID: 36526723, PMCID: PMC10958775, DOI: 10.1038/s41591-022-02094-6.Peer-Reviewed Original ResearchConceptsImmune-related adverse eventsImmune checkpoint inhibitorsGrade immune-related adverse eventsGermline variantsICI initiationCheckpoint inhibitorsAdverse eventsCheckpoint blockadeImproved survivalDiscovery cohortLymphocyte homeostasisSignificant associationCancer typesIL7Remarkable responsePatientsCritical regulatorGenome-wide significant associationAssociationWide association studyIndependent studiesAssociation studiesBlockadeCohortVariantsDual CDKN2A/MTAP loss compared to CDKN2A loss alone and response to immune-checkpoint inhibitors (ICI) in advanced solid tumors.
Adib E, Nassar A, El Zarif T, Kale N, Rakaee M, Mouhieddine T, Abou Alaiwi S, Freeman D, Labban M, Akl E, Haddad R, Hodi F, Sonpavde G, Giannakis M, Braun D, Gusev A, Choueiri T, Overstreet E, Stone E, Kwiatkowski D. Dual CDKN2A/MTAP loss compared to CDKN2A loss alone and response to immune-checkpoint inhibitors (ICI) in advanced solid tumors. Journal Of Clinical Oncology 2022, 40: 2622-2622. DOI: 10.1200/jco.2022.40.16_suppl.2622.Peer-Reviewed Original ResearchImmune checkpoint inhibitorsTumor-infiltrating lymphocytesLow TIL densityTreatment failureOverall survivalHazard ratioTIL densityGenomic alterationsCell carcinomaNon-small cell lung cancerDana-Farber Cancer InstituteCancer typesNeck squamous cell carcinomaAdvanced solid tumorsConcurrent systemic therapyCell lung cancerSquamous cell carcinomaTumor mutational burdenRenal cell carcinomaMelanoma tissue samplesMTAP lossHomozygous deletionECOG PSEsophagogastric carcinomaMetastatic setting