2024
Rechallenging with anti-PD-1 therapy in advanced renal cell carcinoma
Yochum Z, Braun D. Rechallenging with anti-PD-1 therapy in advanced renal cell carcinoma. The Lancet 2024 PMID: 39284326, DOI: 10.1016/s0140-6736(24)01866-x.Peer-Reviewed Original ResearchClinical Implications of Basic Research: Exploring the Transformative Potential of Spatial 'Omics in Uro-oncology
Figiel S, Bates A, Braun D, Eapen R, Eckstein M, Manley B, Milowsky M, Mitchell T, Bryant R, Sfakianos J, Lamb A. Clinical Implications of Basic Research: Exploring the Transformative Potential of Spatial 'Omics in Uro-oncology. European Urology 2024 PMID: 39227262, DOI: 10.1016/j.eururo.2024.08.025.Peer-Reviewed Original ResearchSystematic identification of minor histocompatibility antigens predicts outcomes of allogeneic hematopoietic cell transplantation
Cieri N, Hookeri N, Stromhaug K, Li L, Keating J, Díaz-Fernández P, Gómez-García de Soria V, Stevens J, Kfuri-Rubens R, Shao Y, Kooshesh K, Powell K, Ji H, Hernandez G, Abelin J, Klaeger S, Forman C, Clauser K, Sarkizova S, Braun D, Penter L, Kim H, Lane W, Oliveira G, Kean L, Li S, Livak K, Carr S, Keskin D, Muñoz-Calleja C, Ho V, Ritz J, Soiffer R, Neuberg D, Stewart C, Getz G, Wu C. Systematic identification of minor histocompatibility antigens predicts outcomes of allogeneic hematopoietic cell transplantation. Nature Biotechnology 2024, 1-12. PMID: 39169264, DOI: 10.1038/s41587-024-02348-3.Peer-Reviewed Original ResearchAllogeneic hematopoietic cell transplantationHematopoietic cell transplantationCell transplantationEffect of allogeneic hematopoietic cell transplantationIdentification of minor histocompatibility antigensOutcomes of allogeneic hematopoietic cell transplantationOccurrence of acute GVHDPost-transplant disease recurrenceGraft-versus-host diseaseWhole-exome sequencing of germline DNASequencing of germline DNAGraft-versus-leukemiaT-cell alloreactivityGraft-versus-hostMinor histocompatibility antigensWhole-exome sequencingAcute GVHDPulmonary GVHDAllo-HCTDisease recurrenceHistocompatibility antigensClinical outcomesValidation cohortGermline DNAGVHDFirst-line Systemic Therapy Following Adjuvant Immunotherapy in Renal Cell Carcinoma: An International Multicenter Study
El Zarif T, Semaan K, Xie W, Eid M, Zarba M, Issa W, Zhang T, Nguyen C, Alva A, Fahey C, Beckermann K, Karam J, Campbell M, Procopio G, Stellato M, Buti S, Zemankova A, Melichar B, Massari F, Mollica V, Venugopal B, Ebrahimi H, de Velasco G, Gurney H, De Giorgi U, Parikh O, Winquist E, Master V, Garcia A, Cutuli H, Ferguson T, Gross-Goupil M, Baca S, Pal S, Braun D, McKay R, Heng D, Choueiri T. First-line Systemic Therapy Following Adjuvant Immunotherapy in Renal Cell Carcinoma: An International Multicenter Study. European Urology 2024 PMID: 39147674, DOI: 10.1016/j.eururo.2024.07.016.Peer-Reviewed Original ResearchRenal cell carcinomaProgression-free survivalInternational Metastatic RCC Database ConsortiumRecurrent renal cell carcinomaTreatment-related adverse eventsSystemic therapyAdjuvant pembrolizumabOverall survivalCell carcinomaClinical outcomesIO therapyAdjuvant immunotherapyAdverse eventsVascular endothelial growth factor-targeted therapyDetect occult metastatic diseaseOutcomes of first-lineFirst-line systemic therapyFavorable-risk diseaseIO-based regimensOccult metastatic diseaseMedian follow-upKaplan-Meier methodShort follow-up periodFollow-up periodInternational multicenter studyTIGIT expression in renal cell carcinoma infiltrating T cells is variable and inversely correlated with PD-1 and LAG3
Perales O, Jilaveanu L, Adeniran A, Su D, Hurwitz M, Braun D, Kluger H, Schoenfeld D. TIGIT expression in renal cell carcinoma infiltrating T cells is variable and inversely correlated with PD-1 and LAG3. Cancer Immunology, Immunotherapy 2024, 73: 192. PMID: 39105820, PMCID: PMC11303630, DOI: 10.1007/s00262-024-03773-8.Peer-Reviewed Original ResearchConceptsRenal cell carcinomaRenal cell carcinoma tumorsT cellsTIGIT expressionCheckpoint inhibitorsPD-1Likelihood of response to therapyTumor-infiltrating T cellsCD3+ T cellsRenal cell carcinoma metastasisTreatment of renal cell carcinomaImmune checkpoint inhibitorsInfiltrating T cellsPurposeImmune checkpoint inhibitorsResponse to therapyT cell immunoglobulinCD3+ levelsMetastatic RCC specimensAdjacent normal renal tissuesNormal renal tissuesQuantitative immunofluorescence analysisCell carcinomaResistant diseasePotential therapeutic targetTissue microarray14 Natural killer cells have impaired cytotoxicity in advanced renal cell carcinoma
Moritz V, Xu W, Birch G, Meliki A, Bharadwaj M, Schindler N, Labaki C, Saliby R, Dinh K, Horst J, Sun M, Kashima S, Machaalani M, Lee G, Hurwitz M, McGregor B, Hirsch M, Shukla S, McDermott D, Signoretti S, Romee R, Choueiri T, Braun D. 14 Natural killer cells have impaired cytotoxicity in advanced renal cell carcinoma. The Oncologist 2024, 29: s7-s8. PMCID: PMC11301877, DOI: 10.1093/oncolo/oyae181.012.Peer-Reviewed Original ResearchNK cell phenotypeGene expression signaturesNK cell populationK562 target cellsNK cellsRenal cell carcinomaAdvanced ccRCCNK cell clustersLocalized ccRCCAnti-tumor activityNormal kidneyNatural killerCell carcinomaMarkers of tissue residencyAdvanced renal cell carcinomaProportion of NK cellsFunction of NK cellsExpression of cytotoxic genesTarget cellsNK cell dysfunctionTotal immune cellsNK cell subsetsCell phenotypeCell populationsCell renal cell carcinomaDevelopment of anex vivo patient-derived tumor model (PDTM) to assess the tumor microenvironment in renal cell carcinoma (RCC)
Kashima S, Gupta R, Moritz V, Sadak K, Adeniran A, Humphrey P, Dinulescu D, Palmer D, Hammond S, Bosenberg M, Hurwitz M, Kenney P, Braun D. Development of anex vivo patient-derived tumor model (PDTM) to assess the tumor microenvironment in renal cell carcinoma (RCC). The Oncologist 2024, 29: s5-s6. PMCID: PMC11301923, DOI: 10.1093/oncolo/oyae181.008.Peer-Reviewed Original ResearchRCC tumor microenvironmentPatient-derived tumor modelsRenal cell carcinomaImmune checkpoint inhibitorsT cell functionPeripheral blood mononuclear cellsEnzyme-linked immunosorbent assayTumor microenvironmentT cellsFlow cytometryTumor fragmentsIFN-gTumor modelTumor samplesCytokine productionHealthy donor peripheral blood mononuclear cellsImpact of immune checkpoint inhibitorsAnti-PD-1 monoclonal antibodyDonor peripheral blood mononuclear cellsCD4+CD25+ regulatory T cellsCD8+ T cell populationsResection of renal cell carcinomaSurgical resection of renal cell carcinomaAnti-PD-1 antibodyMetastatic renal cell carcinoma20 Evaluating intermediate endpoints for overall survival in metastatic renal cell carcinoma treated with immune checkpoint inhibitors: an IMDC study
Saliby R, Xie W, Wells C, Saad E, Eid M, Semaan K, Labaki C, Ferrier E, Zarba M, Ebrahimi H, Ravi P, Suarez C, Morales J, McKay R, Powles T, Wood L, Lalani A, Pal S, de Velasco G, Takemura K, Agarwal N, Braun D, Heng D, Choueiri T. 20 Evaluating intermediate endpoints for overall survival in metastatic renal cell carcinoma treated with immune checkpoint inhibitors: an IMDC study. The Oncologist 2024, 29: s8-s9. PMCID: PMC11301915, DOI: 10.1093/oncolo/oyae181.013.Peer-Reviewed Original ResearchTime to next therapyInternational mRCC Database ConsortiumTime to treatment failureInternational mRCC Database Consortium risk groupOverall survivalObjective responseFollow-upIndividual patient dataLandmark analysisTreatment failureInternational Metastatic Renal-Cell Carcinoma Database ConsortiumMetastatic renal cell carcinoma treated with immune checkpoint inhibitorsRisk groupsEndpoint of overall survivalMonths of follow-upIntermediate endpointsICI-based regimensImmune checkpoint inhibitorsImmune-checkpoint inhibitorsMedian follow-upAnalysis of OSAssociated with OSAssociation of OSPost-therapy initiationFollow-up time46 Radiological tumor burden is an independent risk factor for survival in patients with metastatic clear cell renal cell carcinoma (mccRCC) treated with first line immunotherapy (IO)-based regimens
Nawfal R, Eid M, Semaan K, Paul M, Saliby R, Chehade R, Machaalani M, Phillips N, Canniff J, Saad E, Vasseur D, Zarif T, Yekeduz E, Sun M, Baca S, Braun D, Xie W, Krajewski K, Choueiri T. 46 Radiological tumor burden is an independent risk factor for survival in patients with metastatic clear cell renal cell carcinoma (mccRCC) treated with first line immunotherapy (IO)-based regimens. The Oncologist 2024, 29: s25-s26. PMCID: PMC11301862, DOI: 10.1093/oncolo/oyae181.041.Peer-Reviewed Original ResearchIO-based regimensTumor burdenOverall survivalTreatment failureMultivariate analysisPrognostic factorsCT scanMetastatic clear cell renal cell carcinomaAssociated with treatment failureMultivariate Cox regression modelClear cell renal cell carcinomaHistory of nephrectomyIMDC risk groupsImmunotherapy-based regimensAssociated with OSMedian follow-upCell renal cell carcinomaDana-Farber Cancer InstituteLog-rank testIndependent risk factorRenal cell carcinomaKaplan-Meier curvesCT scan reportsManagement of patientsCox regression models22 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 inhibitors24 Applying genomic analysis to refine unclassified renal cell carcinoma
Yekeduz E, Braun D, Chehade R, Eid M, Labaki C, Machaalani M, Nassar A, Nawfal R, Saad E, Saliby R, Semaan K, Sun M, Hirsch M, Ürün Y, Zarif T, Choueiri T. 24 Applying genomic analysis to refine unclassified renal cell carcinoma. The Oncologist 2024, 29: s20-s20. PMCID: PMC11301928, DOI: 10.1093/oncolo/oyae181.032.Peer-Reviewed Original ResearchRenal cell carcinomaClear cell RCCRenal cell carcinoma subtypesAmerican Association for Cancer ResearchPapillary RCCGenomic alterationsOverall survivalNF2 alterationsCell carcinomaGenomic profilingPapillary renal cell carcinomaSubtype of renal cell carcinomaChromophobe renal cell carcinomaProportion of female patientsClear cell renal cell carcinomaMedian overall survivalCell renal cell carcinomaFrequent genomic alterationsCo-mutated genesCompare categorical variablesBenjamini-Hochberg correctionOncogenic signaling pathwaysMetastatic sitesFrequent subtype of renal cell carcinomaPrimary tumor44 Liquid biopsy epigenomic profiling for the detection of sarcomatoid renal cell carcinoma
Semaan K, Zarif T, Eid M, Canniff J, Phillips N, Fortunato B, Savignano H, Davidson M, Chehade R, Garinet S, Saad E, Saliby R, Sun M, Seo J, Berchuck J, Braun D, Freedman M, Choueiri T, Baca S. 44 Liquid biopsy epigenomic profiling for the detection of sarcomatoid renal cell carcinoma. The Oncologist 2024, 29: s4-s5. PMCID: PMC11301903, DOI: 10.1093/oncolo/oyae181.006.Peer-Reviewed Original ResearchRenal cell carcinomaCell-free DNASarcomatoid differentiationRegulatory elementsArea under the receiver operating characteristicCell carcinomaChIP-seqResponse to immune checkpoint blockadeSarcomatoid renal cell carcinomaHistological subtypes of cancerAssociated with poor survivalImmune checkpoint blockadeDana-Farber Cancer InstituteChIP-seq signalsHistone modification signalsActive regulatory elementsArea under the receiver operating characteristic curveWilcoxon rank sum testTissue samplesCell-free chromatinRank sum testReceiver operating characteristicCheckpoint blockadeFrozen tissue samplesEpithelioid subtypePAK4-targeted PROTACs in clear cell renal cell carcinoma: a two-for-one targeted and immune therapy?
Bakouny Z, Braun D, Reznik E, Hakimi A. PAK4-targeted PROTACs in clear cell renal cell carcinoma: a two-for-one targeted and immune therapy? EBioMedicine 2024, 105: 105218. PMID: 38924842, PMCID: PMC11259692, DOI: 10.1016/j.ebiom.2024.105218.Peer-Reviewed Original ResearchEpigenomic signatures of sarcomatoid differentiation to guide the treatment of renal cell carcinoma
El Zarif T, Semaan K, Eid M, Seo J, Garinet S, Davidsohn M, Sahgal P, Fortunato B, Canniff J, Nassar A, Abou Alaiwi S, Bakouny Z, Lakshminarayanan G, Savignano H, Lyons K, Matar S, Ali A, Saad E, Saliby R, Cordeiro P, Zhang Z, El Ahmar N, Laimon Y, Labaki C, Shah V, Freeman D, O'Toole J, Lee G, Hwang J, Pomerantz M, Signoretti S, Van Allen E, Xie W, Berchuck J, Viswanathan S, Braun D, Choueiri T, Freedman M, Baca S. Epigenomic signatures of sarcomatoid differentiation to guide the treatment of renal cell carcinoma. Cell Reports 2024, 43: 114350. PMID: 38870013, DOI: 10.1016/j.celrep.2024.114350.Peer-Reviewed Original ResearchImmune checkpoint inhibitorsRenal cell carcinomaSarcomatoid differentiationCell carcinomaResponse to immune checkpoint inhibitorsGene regulatory programsAssociated with poor survivalTreatment of renal cell carcinomaLow diagnostic yieldRandomized clinical trialsCheckpoint inhibitorsTumor histologyEpigenomic signaturesTranscription factor FOSL1Healthy volunteersPatient plasmaPoor survivalLiquid biopsyFOSL1 expressionClinical trialsProfiling histone modificationsDiagnostic approachImprove outcomesRegulatory programsPlasma samplesEmerging Novel Functional Imaging and Immunotherapy in Renal Cell Carcinoma and Current Treatment Sequencing Strategies After Immunotherapy.
Ali M, Eid M, Saliby R, Choi S, McKay R, Siva S, Braun D, Chen Y. Emerging Novel Functional Imaging and Immunotherapy in Renal Cell Carcinoma and Current Treatment Sequencing Strategies After Immunotherapy. American Society Of Clinical Oncology Educational Book 2024, 44: e438658. PMID: 38875505, DOI: 10.1200/edbk_438658.Peer-Reviewed Original ResearchConceptsRenal cell carcinomaTreatment sequencing strategiesCell carcinomaImmune checkpoint inhibitors targeting PD-1Chimeric antigen receptor T-cell therapyCheckpoint inhibitors targeting PD-1Management of renal cell carcinomaAdvanced renal cell carcinomaProstate-specific membrane antigenLandscape of renal cell carcinomaRCC-associated antigensImmune checkpoint inhibitionT-cell therapyPrimary kidney tumorsAssess treatment responseChanging treatment landscapeCarbonic anhydrase IXFunctional imagingFunctional imaging modalitiesCheckpoint inhibitionPD-1Immunotherapy strategiesLAG-3Membrane antigenT cellsInvestigation of T cell phenotypes associated with response or resistance to immune checkpoint inhibitors (ICI) through single-cell analysis of renal cell carcinoma (RCC).
Kashima S, Ye Z, Meliki A, Hugaboom M, Schindler N, Graham J, Moritz V, El Ahmar N, Nabil Laimon Y, Canniff J, Saliby R, Lee G, Machaalani M, Sun M, Xu W, Signoretti S, McGregor B, McKay R, CHOUEIRI T, Braun D. Investigation of T cell phenotypes associated with response or resistance to immune checkpoint inhibitors (ICI) through single-cell analysis of renal cell carcinoma (RCC). Journal Of Clinical Oncology 2024, 42: 4515-4515. DOI: 10.1200/jco.2024.42.16_suppl.4515.Peer-Reviewed Original ResearchImmune checkpoint inhibitorsRenal cell carcinomaCD8+ T cell infiltrationT cell infiltrationNon-respondersTumor microenvironmentT cellsRCC tumor microenvironmentResistance to immune checkpoint inhibitorsICI responseImmune checkpoint inhibitor treatmentImmune checkpoint inhibitor efficacyCD8+ T cellsExpressed PD-1ICI-treated patientsGene programGene signature scoresTumor mutation loadCellular compositionGene expression signaturesSingle-cell transcriptome analysisCheckpoint inhibitorsPD-1Partial responseSystemic therapyCharacterizing genomic alterations in patients with metastatic urothelial carcinoma (mUC) treated with enfortumab-vedotin (EV) with a focus on 1q23.3.
Saliby R, Semaan K, Epstein I, Liria S, Dall C, Saad E, Eid M, Canniff J, Kwak L, Berg S, Mantia C, McGregor B, Braun D, CHOUEIRI T, Bellmunt J. Characterizing genomic alterations in patients with metastatic urothelial carcinoma (mUC) treated with enfortumab-vedotin (EV) with a focus on 1q23.3. Journal Of Clinical Oncology 2024, 42: e16570-e16570. DOI: 10.1200/jco.2024.42.16_suppl.e16570.Peer-Reviewed Original ResearchMetastatic urothelial carcinomaToxicity-free survivalProgression-free survivalEnfortumab vedotinOverall survivalProgressive diseaseTwo-copy deletionGenomic alterationsClinical outcomesAssociation of genomic alterationsNumerically longer OSDana-Farber Cancer InstituteLog-rank testFisher's exact testUnivariate Cox regressionAdvanced UCLonger OSUrothelial carcinomaSomatic alterationsDana-FarberExact testCox regressionEV efficacyPatientsImprove outcomesApplying genomic analysis to refine unclassified renal cell carcinoma.
Yekeduz E, Braun D, El Hajj Chehade R, Eid M, Labaki C, Machaalani M, Nassar A, Nawfal R, Saad E, Saliby R, Semaan K, Sun M, Hirsch M, Ürün Y, El Zarif T, CHOUEIRI T. Applying genomic analysis to refine unclassified renal cell carcinoma. Journal Of Clinical Oncology 2024, 42: 4551-4551. DOI: 10.1200/jco.2024.42.16_suppl.4551.Peer-Reviewed Original ResearchRenal cell carcinomaClear cell RCCRenal cell carcinoma subtypesAmerican Association for Cancer ResearchPapillary RCCGenomic alterationsOverall survivalCell carcinomaGenomic profilingPapillary renal cell carcinomaSubtype of renal cell carcinomaChromophobe renal cell carcinomaProportion of female patientsClear cell renal cell carcinomaMedian overall survivalCell renal cell carcinomaCo-mutated genesCompare categorical variablesBenjamini-Hochberg correctionOncogenic signaling pathwaysMetastatic sitesFrequent subtype of renal cell carcinomaPrimary tumorChi-square testNF2 alterationsMolecular analysis of the HCRN GU16-260-Cohort A phase II study of first-line (1L) nivolumab (nivo) and salvage nivo + ipilimumab (ipi) in patients (pts) with advanced clear cell renal cell carcinoma (accRCC).
Zaemes J, Hugaboom M, Shah V, Haas N, McDermott D, Jegede O, Bilen M, Stein M, Sosman J, Alter R, Plimack E, Hurwitz M, Wu C, Einstein D, Hammers H, Signoretti S, West D, Denize T, Atkins M, Braun D. Molecular analysis of the HCRN GU16-260-Cohort A phase II study of first-line (1L) nivolumab (nivo) and salvage nivo + ipilimumab (ipi) in patients (pts) with advanced clear cell renal cell carcinoma (accRCC). Journal Of Clinical Oncology 2024, 42: 4546-4546. DOI: 10.1200/jco.2024.42.16_suppl.4546.Peer-Reviewed Original ResearchObjective response rateImmune checkpoint blockadeProgression-free survivalProgressive diseaseAnti-VEGFOverall survivalAssociated with higher progression-free survivalTumor samplesAdvanced clear cell renal cell carcinomaCombined immune checkpoint blockadeHigher progression-free survivalIncreased PFSImmune checkpoint blockade therapyShorter progression-free survivalClear cell renal cell carcinomaAnti-VEGF therapyCell renal cell carcinomaWeeks of therapyRenal cell carcinomaBiomarkers of efficacyFFPE tumor samplesNIVO monotherapyCheckpoint blockadeDecreased OSProspective trialsExpression of the receptor tyrosine kinase AXL and clinical outcomes to cabozantinib and everolimus in patients with metastatic renal cell carcinoma enrolled in the METEOR trial.
Nabil Laimon Y, Paul M, Ghandour F, El Ahmar N, Matar S, Denize T, Bagheri Sheshdeh A, Savla V, Mohanna R, Sun M, Saliby R, Saad E, Machaalani M, Braun D, Aftab D, Xie W, CHOUEIRI T, Signoretti S. Expression of the receptor tyrosine kinase AXL and clinical outcomes to cabozantinib and everolimus in patients with metastatic renal cell carcinoma enrolled in the METEOR trial. Journal Of Clinical Oncology 2024, 42: 4543-4543. DOI: 10.1200/jco.2024.42.16_suppl.4543.Peer-Reviewed Original ResearchProgression-free survivalAssociated with progression-free survivalReceptor tyrosine kinase AXLTyrosine kinase inhibitorsRenal cell carcinomaImmune cellsMETEOR trialTyrosine kinase AXLAxl expressionTumor cellsCell carcinomaAssociated with shorter progression-free survivalMetastatic clear cell renal cell carcinomaAnti-PD-1 therapyLevels of AXL expressionMetastatic renal cell carcinomaMultitargeted tyrosine kinase inhibitorPresence of bone metastasesShorter progression-free survivalClear cell renal cell carcinomaIMDC risk groupsPretreatment tumor tissueVEGFR-TKI treatmentCell renal cell carcinomaDouble immunohistochemistry staining