FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W4200619962> ?p ?o ?g. }

• W4200619962 endingPage "S1378" @default.
• W4200619962 startingPage "S1378" @default.
• W4200619962 abstract "BackgroundImmune checkpoint inhibitors have revolutionised the management of NSCLC. However, the development of irAEs is associated with morbidity that can be lifelong and even fatal. While it has been suggested that human leukocyte antigen (HLA-I) homozygosity is associated with worse overall survival among NSCLC treated with single agent immunotherapy, its association with toxicity has not been examined.MethodsWe collected blood from 193 NSCLC patients treated with anti-PD1/L1 in the first- or second-line setting. Blood cells DNA was extracted and high-quality HLA typing performed. Toxicity data was collected and graded as per common terminology criteria for adverse event (CTCAE) V5.0. Univariate analysis using GraphPad Prism was used to correlate between HLA-I/II heterozygosity with toxicity. We investigated the relationship between toxicity, overall response rate (ORR), progression free survival (PFS) and overall survival (OS). In addition, we investigated the association between irAEs and different HLA-I/II supertypes and genotypes.ResultsWe recorded 103 irAE among 179 patients suitable for analysis. Homozygosity at one or more HLA-I loci, but not HLA-II, was associated with reduced risk of irAE (RR=0.57, P=0.025). None of the patients with homozygosity at one or more HLA-I loci developed pneumonitis of any grade (RR=0.00, P=0.037) or grade 3 toxicity (RR=0.00, P=0.023). In addition, the HLA-A03 supertype or the HLA-DRB1*0401 allele were associated with increased risk of developing irAE, (RR=1.40, P=0.039) and (RR=1.51, P=0.023), respectively. None of the patients with HLA-DQB1*0301 experienced gastrointestinal toxicity (RR=0.00, P=0.048). The occurrence of any irAE was associated with improved ORR (RR=1.94, P<0.0001), PFS (HR=0.37, P<0.0001) and OS (HR=0.26, P<0.0001), respectively. The use of steroids to treat irAE did not diminish this association.ConclusionsMaximal HLA-I loci heterozygosity may be a useful biomarker to predict irAEs, especially pneumonitis among NSCLC patients treated with anti-PD1/PD-L1 in the first- or second-line setting. However, the occurrence of any irAE is correlated with favourable clinical outcome.Legal entity responsible for the studyThe authors.FundingHas not received any funding.DisclosureAll authors have declared no conflicts of interest. BackgroundImmune checkpoint inhibitors have revolutionised the management of NSCLC. However, the development of irAEs is associated with morbidity that can be lifelong and even fatal. While it has been suggested that human leukocyte antigen (HLA-I) homozygosity is associated with worse overall survival among NSCLC treated with single agent immunotherapy, its association with toxicity has not been examined. Immune checkpoint inhibitors have revolutionised the management of NSCLC. However, the development of irAEs is associated with morbidity that can be lifelong and even fatal. While it has been suggested that human leukocyte antigen (HLA-I) homozygosity is associated with worse overall survival among NSCLC treated with single agent immunotherapy, its association with toxicity has not been examined. MethodsWe collected blood from 193 NSCLC patients treated with anti-PD1/L1 in the first- or second-line setting. Blood cells DNA was extracted and high-quality HLA typing performed. Toxicity data was collected and graded as per common terminology criteria for adverse event (CTCAE) V5.0. Univariate analysis using GraphPad Prism was used to correlate between HLA-I/II heterozygosity with toxicity. We investigated the relationship between toxicity, overall response rate (ORR), progression free survival (PFS) and overall survival (OS). In addition, we investigated the association between irAEs and different HLA-I/II supertypes and genotypes. We collected blood from 193 NSCLC patients treated with anti-PD1/L1 in the first- or second-line setting. Blood cells DNA was extracted and high-quality HLA typing performed. Toxicity data was collected and graded as per common terminology criteria for adverse event (CTCAE) V5.0. Univariate analysis using GraphPad Prism was used to correlate between HLA-I/II heterozygosity with toxicity. We investigated the relationship between toxicity, overall response rate (ORR), progression free survival (PFS) and overall survival (OS). In addition, we investigated the association between irAEs and different HLA-I/II supertypes and genotypes. ResultsWe recorded 103 irAE among 179 patients suitable for analysis. Homozygosity at one or more HLA-I loci, but not HLA-II, was associated with reduced risk of irAE (RR=0.57, P=0.025). None of the patients with homozygosity at one or more HLA-I loci developed pneumonitis of any grade (RR=0.00, P=0.037) or grade 3 toxicity (RR=0.00, P=0.023). In addition, the HLA-A03 supertype or the HLA-DRB1*0401 allele were associated with increased risk of developing irAE, (RR=1.40, P=0.039) and (RR=1.51, P=0.023), respectively. None of the patients with HLA-DQB1*0301 experienced gastrointestinal toxicity (RR=0.00, P=0.048). The occurrence of any irAE was associated with improved ORR (RR=1.94, P<0.0001), PFS (HR=0.37, P<0.0001) and OS (HR=0.26, P<0.0001), respectively. The use of steroids to treat irAE did not diminish this association. We recorded 103 irAE among 179 patients suitable for analysis. Homozygosity at one or more HLA-I loci, but not HLA-II, was associated with reduced risk of irAE (RR=0.57, P=0.025). None of the patients with homozygosity at one or more HLA-I loci developed pneumonitis of any grade (RR=0.00, P=0.037) or grade 3 toxicity (RR=0.00, P=0.023). In addition, the HLA-A03 supertype or the HLA-DRB1*0401 allele were associated with increased risk of developing irAE, (RR=1.40, P=0.039) and (RR=1.51, P=0.023), respectively. None of the patients with HLA-DQB1*0301 experienced gastrointestinal toxicity (RR=0.00, P=0.048). The occurrence of any irAE was associated with improved ORR (RR=1.94, P<0.0001), PFS (HR=0.37, P<0.0001) and OS (HR=0.26, P<0.0001), respectively. The use of steroids to treat irAE did not diminish this association. ConclusionsMaximal HLA-I loci heterozygosity may be a useful biomarker to predict irAEs, especially pneumonitis among NSCLC patients treated with anti-PD1/PD-L1 in the first- or second-line setting. However, the occurrence of any irAE is correlated with favourable clinical outcome. Maximal HLA-I loci heterozygosity may be a useful biomarker to predict irAEs, especially pneumonitis among NSCLC patients treated with anti-PD1/PD-L1 in the first- or second-line setting. However, the occurrence of any irAE is correlated with favourable clinical outcome." @default.
• W4200619962 created "2021-12-31" @default.
• W4200619962 creator A5000056042 @default.
• W4200619962 creator A5007725356 @default.
• W4200619962 creator A5054900690 @default.
• W4200619962 creator A5070240933 @default.
• W4200619962 creator A5079333634 @default.
• W4200619962 creator A5079833339 @default.
• W4200619962 date "2021-12-01" @default.
• W4200619962 modified "2023-09-26" @default.
• W4200619962 title "9P HLA-I homozygosity as a predictive biomarker for developing immune related adverse events (irAE) among non-small cell lung cancer (NSCLC) patients treated with single agent immunotherapy" @default.
• W4200619962 doi "https://doi.org/10.1016/j.annonc.2021.10.025" @default.
• W4200619962 hasPublicationYear "2021" @default.
• W4200619962 type Work @default.
• W4200619962 citedByCount "0" @default.
• W4200619962 crossrefType "journal-article" @default.
• W4200619962 hasAuthorship W4200619962A5000056042 @default.
• W4200619962 hasAuthorship W4200619962A5007725356 @default.
• W4200619962 hasAuthorship W4200619962A5054900690 @default.
• W4200619962 hasAuthorship W4200619962A5070240933 @default.
• W4200619962 hasAuthorship W4200619962A5079333634 @default.
• W4200619962 hasAuthorship W4200619962A5079833339 @default.
• W4200619962 hasBestOaLocation W42006199621 @default.
• W4200619962 hasConcept C104317684 @default.
• W4200619962 hasConcept C126322002 @default.
• W4200619962 hasConcept C143589142 @default.
• W4200619962 hasConcept C143998085 @default.
• W4200619962 hasConcept C147483822 @default.
• W4200619962 hasConcept C180754005 @default.
• W4200619962 hasConcept C188280979 @default.
• W4200619962 hasConcept C197934379 @default.
• W4200619962 hasConcept C203014093 @default.
• W4200619962 hasConcept C2776256026 @default.
• W4200619962 hasConcept C2777714996 @default.
• W4200619962 hasConcept C2777793932 @default.
• W4200619962 hasConcept C2779524853 @default.
• W4200619962 hasConcept C29730261 @default.
• W4200619962 hasConcept C44249647 @default.
• W4200619962 hasConcept C55493867 @default.
• W4200619962 hasConcept C71924100 @default.
• W4200619962 hasConcept C82789193 @default.
• W4200619962 hasConcept C86803240 @default.
• W4200619962 hasConceptScore W4200619962C104317684 @default.
• W4200619962 hasConceptScore W4200619962C126322002 @default.
• W4200619962 hasConceptScore W4200619962C143589142 @default.
• W4200619962 hasConceptScore W4200619962C143998085 @default.
• W4200619962 hasConceptScore W4200619962C147483822 @default.
• W4200619962 hasConceptScore W4200619962C180754005 @default.
• W4200619962 hasConceptScore W4200619962C188280979 @default.
• W4200619962 hasConceptScore W4200619962C197934379 @default.
• W4200619962 hasConceptScore W4200619962C203014093 @default.
• W4200619962 hasConceptScore W4200619962C2776256026 @default.
• W4200619962 hasConceptScore W4200619962C2777714996 @default.
• W4200619962 hasConceptScore W4200619962C2777793932 @default.
• W4200619962 hasConceptScore W4200619962C2779524853 @default.
• W4200619962 hasConceptScore W4200619962C29730261 @default.
• W4200619962 hasConceptScore W4200619962C44249647 @default.
• W4200619962 hasConceptScore W4200619962C55493867 @default.
• W4200619962 hasConceptScore W4200619962C71924100 @default.
• W4200619962 hasConceptScore W4200619962C82789193 @default.
• W4200619962 hasConceptScore W4200619962C86803240 @default.
• W4200619962 hasLocation W42006199621 @default.
• W4200619962 hasOpenAccess W4200619962 @default.
• W4200619962 hasPrimaryLocation W42006199621 @default.
• W4200619962 hasRelatedWork W2145683400 @default.
• W4200619962 hasRelatedWork W2161047589 @default.
• W4200619962 hasRelatedWork W2279056333 @default.
• W4200619962 hasRelatedWork W2415042866 @default.
• W4200619962 hasRelatedWork W2795949031 @default.
• W4200619962 hasRelatedWork W2898220903 @default.
• W4200619962 hasRelatedWork W3091031604 @default.
• W4200619962 hasRelatedWork W4282979609 @default.
• W4200619962 hasRelatedWork W4283456184 @default.
• W4200619962 hasRelatedWork W4322742425 @default.
• W4200619962 hasVolume "32" @default.
• W4200619962 isParatext "false" @default.
• W4200619962 isRetracted "false" @default.
• W4200619962 workType "article" @default.