2024
22 Association of a germline single nucleotide polymorphism (SNP) in the interleukin-7 (IL7) gene with immune-related adverse events (irAEs)
Saad E, Mehrabad E, Labaki C, Saliby R, Semaan K, Eid M, Machaalani M, Chehade R, Nawfal R, Sun M, Sharon E, Shah P, Vemula S, Gupta S, Braun D, Van Allen E, Gusev A, Choueiri T. 22 Association of a germline single nucleotide polymorphism (SNP) in the interleukin-7 (IL7) gene with immune-related adverse events (irAEs). The Oncologist 2024, 29: s1-s2. PMCID: PMC11301885, DOI: 10.1093/oncolo/oyae181.003.Peer-Reviewed Original ResearchImmune-related adverse eventsMetastatic non-small cell lung cancerMetastatic renal cell carcinomaImmune checkpoint inhibitorsProgression-free survivalWhole-exome sequencingRecurrent grade 2Overall survivalGrade 2Interleukin-7Single nucleotide polymorphismsNivolumab armPembrolizumab armSomatic alterationsAdverse eventsTreatment armsPrediction of immune-related adverse eventsCumulative rates of adverse eventsTumor whole-exome sequencingRates of grade 2Non-small cell lung cancerGermline single nucleotide polymorphismsClinical trials of patientsAssociated with significantly higher ratesPD-1 inhibitorsAdvanced renal cell cancer combination immunotherapy clinical trial (ARCITECT; HCRN GU 22-587).
Serzan M, Jegede O, Alter R, Bilen M, Braun D, Einstein D, Haas N, Herchenhorn D, King J, Runcie K, Sosman J, Sternberg C, Yang Y, Signoretti S, CHOUEIRI T, Atkins M. Advanced renal cell cancer combination immunotherapy clinical trial (ARCITECT; HCRN GU 22-587). Journal Of Clinical Oncology 2024, 42: tps4614-tps4614. DOI: 10.1200/jco.2024.42.16_suppl.tps4614.Peer-Reviewed Original ResearchTyrosine kinase inhibitorsArm BArm APrimary endpointRate of immune-related adverse eventsMetastatic clear cell renal cell carcinomaImmune-related adverse eventsMolecular predictors of responseVEGF receptor tyrosine kinase inhibitorReceptor tyrosine kinase inhibitorsEnhance T cell primingOne-sided significance levelClear cell renal cell carcinomaAnti-PD1 inhibitorsIMDC risk groupsTreatment free intervalProgression-free survivalT cell primingTreatment-free survivalCell renal cell carcinomaSubpopulations of TregsFirst-line treatmentRenal cell carcinomaPredictors of responseAssociated with increased presenceAdvanced renal cell cancer combination immunotherapy clinical trial (ARCITECT; HCRN GU 22-587).
Serzan M, Jegede O, Bilen M, Braun D, Einstein D, Haas N, Hammers H, King J, Runcie K, Sosman J, Sternberg C, Yang Y, Choueiri T, Signoretti S, Atkins M. Advanced renal cell cancer combination immunotherapy clinical trial (ARCITECT; HCRN GU 22-587). Journal Of Clinical Oncology 2024, 42: tps492-tps492. DOI: 10.1200/jco.2024.42.4_suppl.tps492.Peer-Reviewed Original ResearchTyrosine kinase inhibitorsArm BArm APrimary endpointRate of immune-related adverse eventsMetastatic clear cell renal cell carcinomaImmune-related adverse eventsMolecular predictors of responseVEGF receptor tyrosine kinase inhibitorReceptor tyrosine kinase inhibitorsEnhance T cell primingOne-sided significance levelClear cell renal cell carcinomaAnti-PD1 inhibitorsIMDC risk groupsTreatment free intervalProgression-free survivalT cell primingTreatment-free survivalCell renal cell carcinomaSubpopulations of TregsFirst-line treatmentRenal cell carcinomaPredictors of responseAnti-tumor activity
2022
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 studiesBlockadeCohortVariants