2024
TIGIT 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 microarrayTreatment-free survival outcomes from the phase II study of nivolumab and salvage nivolumab/ipilimumab in advanced clear cell renal cell carcinoma (HCRN GU16-260-Cohort A)
Atkins M, Jegede O, Haas N, Mcdermott D, Bilen M, Stein M, Sosman J, Alter R, Plimack E, Ornstein M, Hurwitz M, Peace D, Einstein D, Catalano P, Hammers H, Regan M. Treatment-free survival outcomes from the phase II study of nivolumab and salvage nivolumab/ipilimumab in advanced clear cell renal cell carcinoma (HCRN GU16-260-Cohort A). Journal For ImmunoTherapy Of Cancer 2024, 12: e008293. PMID: 38604810, PMCID: PMC11015345, DOI: 10.1136/jitc-2023-008293.Peer-Reviewed Original ResearchConceptsTreatment-free survivalInternational Metastatic RCC Database ConsortiumFavorable-risk patientsNivolumab monotherapyPhase II study of nivolumabCessation of immunotherapyFavorable-risk diseaseProtocol therapy cessationStudy of nivolumabSystemic therapy initiationTreatment naive patientsPhase II studyRenal cell carcinomaKaplan-Meier curvesActive treatment approachPartitioned survival analysisCheckMate 067Stable diseaseProtocol therapyAdvanced melanomaTherapy initiationTreatment-freeCell carcinomaClear-cellProtocol treatmentArea Vulnerability and Disparities in Therapy for Patients With Metastatic Renal Cell Carcinoma
Rahman S, Long J, Westvold S, Leapman M, Spees L, Hurwitz M, McManus H, Gross C, Wheeler S, Dinan M. Area Vulnerability and Disparities in Therapy for Patients With Metastatic Renal Cell Carcinoma. JAMA Network Open 2024, 7: e248747. PMID: 38687479, PMCID: PMC11061765, DOI: 10.1001/jamanetworkopen.2024.8747.Peer-Reviewed Original ResearchConceptsMetastatic renal cell carcinomaArea-level measuresRenal cell carcinomaPatient-level factorsSystemic therapyEthnic disparitiesRelative risk ratiosSocially vulnerable areasCell carcinomaMeasures of social vulnerabilityMedicare beneficiariesCohort studyFee-for-service Medicare Parts AOdds ratioReceipt of systemic therapyLogistic regressionArea-level characteristicsAssociated with lack of treatmentNon-Hispanic blacksRetrospective cohort studyIndividual-level demographicsNon-Hispanic whitesAssociated with disparitiesUS Medicare beneficiariesMeasures of disadvantage
2023
Immune dysfunction revealed by digital spatial profiling of immuno-oncology markers in progressive stages of renal cell carcinoma and in brain metastases
Schoenfeld D, Moutafi M, Martinez S, Djureinovic D, Merkin R, Adeniran A, Braun D, Signoretti S, Choueiri T, Parisi F, Hurwitz M, Rimm D, Wei W, Jilaveanu L, Kluger H. Immune dysfunction revealed by digital spatial profiling of immuno-oncology markers in progressive stages of renal cell carcinoma and in brain metastases. Journal For ImmunoTherapy Of Cancer 2023, 11: e007240. PMID: 37586773, PMCID: PMC10432651, DOI: 10.1136/jitc-2023-007240.Peer-Reviewed Original ResearchMeSH KeywordsBrain NeoplasmsCarcinoma, Renal CellHepatitis A Virus Cellular Receptor 2HumansImmune System DiseasesKidney NeoplasmsMedical OncologyTumor MicroenvironmentConceptsRenal cell carcinomaBrain metastasesPrimary tumorTumor microenvironmentDigital spatial profilingCell carcinomaActivation protein expressionInflammatory macrophage markersRCC brain metastasesInnate immune activatorsNormal kidney samplesProgressive stagesExtracranial metastasesTim-3Immune checkpointsImmune dysfunctionImmune activationRCC metastasisLonger survivalImmune activatorsMacrophage markersTreatment responseSeparate cohortTissue microarrayMetastatic samplesDisparities in immune and targeted therapy utilization for older US patients with metastatic renal cell carcinoma
Chow R, Long J, Hassan S, Wheeler S, Spees L, Leapman M, Hurwitz M, McManus H, Gross C, Dinan M. Disparities in immune and targeted therapy utilization for older US patients with metastatic renal cell carcinoma. JNCI Cancer Spectrum 2023, 7: pkad036. PMID: 37202354, PMCID: PMC10276895, DOI: 10.1093/jncics/pkad036.Peer-Reviewed Original ResearchMeSH KeywordsAgedCarcinoma, Renal CellEthnicityFemaleHumansKidney NeoplasmsMaleMedicareUnited StatesWhiteConceptsOral anticancer agentsTherapy utilizationMedicare beneficiariesNon-Hispanic white raceMetastatic renal cell carcinomaNon-Hispanic black raceOlder US patientsUS Medicare beneficiariesRenal cell carcinomaLogistic regression modelsTherapy receiptMultivariable adjustmentSystemic therapyMale sexUS patientsCell carcinomaStudy criteriaBlack raceFemale sexPatient raceWhite raceImmunotherapyOutcomes persistSexPatientsPhase II study of nivolumab and salvage nivolumab/ipilimumab in treatment-naïve patients with advanced non-clear cell renal cell carcinoma (HCRN GU16-260-Cohort B)
Atkins M, Jegede O, Haas N, McDermott D, Bilen M, Stein M, Sosman J, Alter R, Plimack E, Ornstein M, Hurwitz M, Peace D, Signoretti S, Denize T, Cimadamore A, Wu C, Braun D, Einstein D, Catalano P, Hammers H. Phase II study of nivolumab and salvage nivolumab/ipilimumab in treatment-naïve patients with advanced non-clear cell renal cell carcinoma (HCRN GU16-260-Cohort B). Journal For ImmunoTherapy Of Cancer 2023, 11: e004780. PMID: 36948504, PMCID: PMC10040058, DOI: 10.1136/jitc-2022-004780.Peer-Reviewed Original ResearchMeSH KeywordsCarcinoma, Renal CellHumansIpilimumabNivolumabSalvage TherapySarcomaSoft Tissue NeoplasmsConceptsNivolumab/ipilimumabObjective response rateNon-clear cell renal cell carcinomaTreatment-naïve patientsCell renal cell carcinomaProgressive diseaseRenal cell carcinomaNivolumab monotherapyStable diseaseCell carcinomaAdvanced non-clear cell renal cell carcinomaMedian progression-free survivalTreatment-related adverse eventsDeath ligand 1 (PD-L1) expressionLigand 1 expressionPhase II studyProgression-free survivalWeeks of treatmentSymptomatic disease progressionEligible patientsSalvage therapyB patientsII studySalvage treatmentSarcomatoid featuresOutcomes With Combination Pembrolizumab and Axitinib in Second and Further Line Treatment of Metastatic Renal Cell Carcinoma
Dizman N, Austin M, Considine B, Jessel S, Schoenfeld D, Merl M, Hurwitz M, Sznol M, Kluger H. Outcomes With Combination Pembrolizumab and Axitinib in Second and Further Line Treatment of Metastatic Renal Cell Carcinoma. Clinical Genitourinary Cancer 2023, 21: 221-229. PMID: 36681606, DOI: 10.1016/j.clgc.2023.01.002.Peer-Reviewed Original ResearchMeSH KeywordsAxitinibCarcinoma, Renal CellHumansKidney NeoplasmsProspective StudiesRetrospective StudiesVascular Endothelial Growth Factor AConceptsMetastatic renal cell carcinomaPembrolizumab/axitinibObjective response rateProgression-free survivalImmune checkpoint inhibitorsMedian progression-free survivalAdverse eventsRenal cell carcinomaCell carcinomaClear cell metastatic renal cell carcinomaVascular endothelial growth factor receptor tyrosine kinase inhibitorsGrowth factor receptor tyrosine kinase inhibitorsCombination immune checkpoint inhibitorsGrade 5 adverse eventsPrior immune checkpoint inhibitorsSuperior progression-free survivalReceptor tyrosine kinase inhibitorsYale-New Haven HospitalFurther-line treatmentNivolumab/ipilimumabRECIST 1.1 criteriaResponse-evaluable patientsDisease control rateSecond-line therapyFirst-line treatment