2024
Decoy-resistant IL-18 reshapes the tumor microenvironment and enhances rejection by anti-CTLA-4 in renal cell carcinoma
Schoenfeld D, Djureinovic D, Su D, Zhang L, Lu B, Kamga L, Mann J, Huck J, Hurwitz M, Braun D, Jilaveanu L, Ring A, Kluger H. Decoy-resistant IL-18 reshapes the tumor microenvironment and enhances rejection by anti-CTLA-4 in renal cell carcinoma. JCI Insight 2024 PMID: 39561007, DOI: 10.1172/jci.insight.184545.Peer-Reviewed Original ResearchAnti-CTLA-4Renal cell carcinomaIL-18IL-18BPCell carcinomaTumor microenvironmentTumor typesPatients treated with immune checkpoint inhibitorsRegulatory T cell levelsAnti-PD-1 treatmentCD8+ T cellsAnti-PD-1Immune checkpoint inhibitorsCell renal cell carcinomaNon-responder patientsMyeloid cell populationsT cell levelsCytokine interleukin-18Anti-cancer efficacySecreted binding proteinCheckpoint inhibitorsResponding patientsPreclinical modelsT cellsMurine modelCost trends of metastatic renal cell carcinoma therapy: the impact of oral anticancer agents and immunotherapy
Forman R, Long J, Westvold S, Agnish K, McManus H, Leapman M, Hurwitz M, Spees L, Wheeler S, Gross C, Dinan M. Cost trends of metastatic renal cell carcinoma therapy: the impact of oral anticancer agents and immunotherapy. JNCI Cancer Spectrum 2024, 8: pkae067. PMID: 39133171, PMCID: PMC11376369, DOI: 10.1093/jncics/pkae067.Peer-Reviewed Original ResearchMetastatic renal cell carcinomaOral anticancer agentsOAA useAssociated with decreased adherenceRenal cell carcinomaAnticancer agentsDays of treatmentCombination therapyCell carcinomaStudy patientsInitial treatmentReal-world costsCombination groupImmunotherapyPatientsOOP costsTherapyTreatment typePercent daysPerspective of payersTreatmentClaims dataMedicare patientsAnalyzed differencesFee-for-service MedicareTIGIT 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 carcinomaSLAMF7+ CD8+ T cells exhibit decreased anti-tumor responses in renal cell carcinoma
Wirth L, Hugaboom M, Street K, Ruthen N, Jegede O, Schindler N, McDermott D, Plimack E, Sosman J, Haas N, Hurwitz M, Hammers H, Signoretti S, Atkins M, Wu C, Braun D. SLAMF7+ CD8+ T cells exhibit decreased anti-tumor responses in renal cell carcinoma. The Journal Of Immunology 2024, 212: 1491_5876-1491_5876. DOI: 10.4049/jimmunol.212.supp.1491.5876.Peer-Reviewed Original ResearchCD8+ T cellsImmune-checkpoint inhibitorsRenal cell carcinomaCD8+ T-cell effector functionT cell effector functionT cellsCell carcinomaResistance to immune-checkpoint inhibitorsEffector functionsPopulation of CD8+ T cellsCD3+ T cellsTreatment of renal cell carcinomaHealthy human PBMCTumor-infiltrating lymphocytesAnti-tumor responsesPatient T cellsReduction of pro-inflammatory cytokinesAnti-tumor functionPro-inflammatory cytokinesSingle-cell transcriptome analysisNivolumab monotherapySLAMF7 expressionClinical benefitGranzyme BIFN-gTreatment-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
Total and treatment-related costs of care associated with in patients with metastatic renal cell carcinoma receiving targeted or immune therapy.
Rahman S, Long J, Westvold S, Wheeler S, Spees L, Leapman M, Hurwitz M, McManus H, Gross C, Dinan M. Total and treatment-related costs of care associated with in patients with metastatic renal cell carcinoma receiving targeted or immune therapy. JCO Oncology Practice 2023, 19: 28-28. DOI: 10.1200/op.2023.19.11_suppl.28.Peer-Reviewed Original ResearchMetastatic renal cell carcinomaOral anticancer agentsInitial treatmentRetrospective cohort studyUse of immunotherapyYear of diagnosisRenal cell carcinomaDirect treatment costsMean Medicare paymentsMedicare paymentsMedicare Part DInitial therapyCohort studyMetastatic diagnosisCell carcinomaCombination therapyImmunotherapyMedicare beneficiariesPatientsAge 65Disease controlOlder ageStudy periodTherapyDiagnosisImmune 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 ResearchConceptsRenal 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 ResearchConceptsOral 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 ResearchConceptsNivolumab/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 featuresEvolution of systemic therapy from 2015 to 2019 for older patients in the United States 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. Evolution of systemic therapy from 2015 to 2019 for older patients in the United States with metastatic renal cell carcinoma. Journal Of Clinical Oncology 2023, 41: 610-610. DOI: 10.1200/jco.2023.41.6_suppl.610.Peer-Reviewed Original ResearchMetastatic renal cell carcinomaImmune checkpoint inhibitorsOral anti-cancer agentsNon-Hispanic white patientsSystemic therapyRenal cell carcinomaNHW patientsWhite patientsCell carcinomaMedicare beneficiariesService Medicare Parts ARetrospective cohort studyOverall treatment rateMedicare Part AIO therapyMRCC therapyAnti-cancer agentsCheckpoint inhibitorsCohort studyOlder patientsRandomized trialsSurvival improvementFirst therapyStudy criteriaTreatment receiptTreatment-free survival (TFS) outcomes from the phase II study of nivolumab and salvage nivolumab + ipilimumab in advanced clear cell renal cell carcinoma (aRCC) (HCRN GU16-260-Cohort A).
Atkins M, Jegede O, McDermott D, Haas N, Bilen M, Stein M, Sosman J, Plimack E, Alter R, Ornstein M, Hurwitz M, Peace D, Einstein D, Catalano P, Hammers H, Regan M. Treatment-free survival (TFS) outcomes from the phase II study of nivolumab and salvage nivolumab + ipilimumab in advanced clear cell renal cell carcinoma (aRCC) (HCRN GU16-260-Cohort A). Journal Of Clinical Oncology 2023, 41: 604-604. DOI: 10.1200/jco.2023.41.6_suppl.604.Peer-Reviewed Original ResearchAdvanced clear cell renal cell carcinomaTreatment-related adverse eventsGrade 3Clear cell renal cell carcinomaActive treatment approachCheckMate 067 trialCheckMate 214 trialFurther anticancer therapyNivolumab/ipilimumabProlonged disease controlPhase II studyCell renal cell carcinomaKaplan-Meier curvesRenal cell carcinomaNivolumab monotherapyStable diseaseEligible patientsProtocol therapyTherapy initiationII studyTherapy cessationAdverse eventsSurvival outcomesCell carcinomaMetastatic melanomaOutcomes 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 ResearchConceptsMetastatic 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
2020
Phase II study of nivolumab and salvage nivolumab + ipilimumab in treatment-naïve patients (pts) with advanced renal cell carcinoma (RCC) (HCRN GU16-260).
Atkins M, Jegede O, Haas N, McDermott D, Bilen M, Drake C, Sosman J, Alter R, Plimack E, Rini B, Hurwitz M, Peace D, Signoretti S, Wu C, Catalano P, Hammers H. Phase II study of nivolumab and salvage nivolumab + ipilimumab in treatment-naïve patients (pts) with advanced renal cell carcinoma (RCC) (HCRN GU16-260). Journal Of Clinical Oncology 2020, 38: 5006-5006. DOI: 10.1200/jco.2020.38.15_suppl.5006.Peer-Reviewed Original ResearchRenal cell carcinomaProgressive diseaseStable diseaseGrade 3Sarcomatoid histologyPoor-risk renal-cell carcinomaAdvanced renal cell carcinomaMedian age 65Symptomatic progressive diseaseTreatment-related AEsTreatment-naïve patientsPhase II studyWk of treatmentEligible ptsImDC groupIpilimumab combinationMedian DoRMedian PFSSalvage therapyRespiratory failureSalvage treatmentII studyClinical outcomesMetastatic lesionsCell carcinomaAssociation of cytoreductive nephrectomy and survival in the immune checkpoint inhibitor era.
Miccio J, Ma S, Oladeru O, Yang D, Peters G, Jethwa K, Park H, Hurwitz M, Leapman M, Sprenkle P, Nguyen P, Yu J, Johung K. Association of cytoreductive nephrectomy and survival in the immune checkpoint inhibitor era. Journal Of Clinical Oncology 2020, 38: 748-748. DOI: 10.1200/jco.2020.38.6_suppl.748.Peer-Reviewed Original ResearchMetastatic renal cell carcinomaCytoreductive nephrectomyICI eraImproved overall survivalNational Cancer DatabaseOverall survivalIFN eraFuhrman gradeBenefit of CNEfficacy of ICIsClinical T stageCox regression analysisTreatment facility typeRenal cell carcinomaCARMENA trialInterferon eraMultivariable associateN0 diseaseOS benefitProspective reevaluationMedian ageT stageCell carcinomaCancer DatabasePartial nephrectomy