2023
Subsets of IFN Signaling Predict Response to Immune Checkpoint Blockade in Patients with Melanoma.
Horowitch B, Lee D, Ding M, Martinez-Morilla S, Aung T, Ouerghi F, Wang X, Wei W, Damsky W, Sznol M, Kluger H, Rimm D, Ishizuka J. Subsets of IFN Signaling Predict Response to Immune Checkpoint Blockade in Patients with Melanoma. Clinical Cancer Research 2023, 29: 2908-2918. PMID: 37233452, PMCID: PMC10524955, DOI: 10.1158/1078-0432.ccr-23-0215.Peer-Reviewed Original ResearchConceptsImmune checkpoint inhibitorsHuman melanoma cell linesMelanoma cell linesPD-L1Validation cohortYale-New Haven HospitalCombination of ipilimumabPD-L1 markersImmune checkpoint blockadePD-L1 biomarkerNew Haven HospitalSTAT1 levelsCell linesWestern blot analysisCheckpoint inhibitorsCheckpoint blockadeClinical responseOverall survivalImproved survivalResistance of cancersMetastatic melanomaMelanoma responsePredict responseTreatment responseDistinct patternsValidation of the Prognostic Usefulness of the Gene Expression Profiling Test in Patients with Uveal Melanoma
Miguez S, Lee R, Chan A, Demkowicz P, Jones B, Long C, Abramson D, Bosenberg M, Sznol M, Kluger H, Goldbaum M, Francis J, Pointdujour-Lim R, Bakhoum M. Validation of the Prognostic Usefulness of the Gene Expression Profiling Test in Patients with Uveal Melanoma. Ophthalmology 2023, 130: 598-607. PMID: 36739981, PMCID: PMC10619207, DOI: 10.1016/j.ophtha.2023.01.020.Peer-Reviewed Original ResearchConceptsMetastasis-free survivalRisk of metastasisClass 2 tumorsAdditional prognostic valueRate of metastasisPrognostic usefulnessTumor sizeTumor characteristicsPrognostic valueUveal melanomaGene expression profile testingMemorial Sloan-Kettering Cancer CenterGEP classificationCox hazard regression analysisYale-New Haven HospitalHazards regression analysisGene expression profiling testsNew Haven HospitalClass 1 tumorsGEP class 2Class 1AMean followTumor thicknessCancer CenterSurveillance protocolOutcomes 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
2018
Inflammatory eruptions associated with immune checkpoint inhibitor therapy: A single-institution retrospective analysis with stratification of reactions by toxicity and implications for management
Coleman E, Ko C, Dai F, Tomayko MM, Kluger H, Leventhal JS. Inflammatory eruptions associated with immune checkpoint inhibitor therapy: A single-institution retrospective analysis with stratification of reactions by toxicity and implications for management. Journal Of The American Academy Of Dermatology 2018, 80: 990-997. PMID: 30399387, PMCID: PMC6420863, DOI: 10.1016/j.jaad.2018.10.062.Peer-Reviewed Original ResearchMeSH KeywordsAgedAntibodies, MonoclonalAntibodies, Monoclonal, HumanizedAntineoplastic Agents, ImmunologicalAntineoplastic Combined Chemotherapy ProtocolsDrug EruptionsExanthemaFemaleHumansIpilimumabLichenoid EruptionsMaleMiddle AgedNivolumabRetrospective StudiesSkin NeoplasmsStevens-Johnson SyndromeWithholding TreatmentConceptsInflammatory eruptionsCheckpoint inhibitorsTherapeutic responseImmune checkpoint inhibitor therapySingle tertiary care centerSingle-institution retrospective analysisYale-New Haven HospitalCheckpoint inhibitor therapyTertiary care centerMinority of patientsInpatient dermatology serviceDegree of severityMost rashesInhibitor therapyRetrospective studyTopical treatmentEarly recognitionMedical recordsCare centerInflammatory reactionRetrospective analysisDermatology servicesImmunotherapyMean latencyGrade 2
2017
Stereotactic radiosurgery of early melanoma brain metastases after initiation of anti-CTLA-4 treatment is associated with improved intracranial control
An Y, Jiang W, Kim BYS, Qian JM, Tang C, Fang P, Logan J, D'Souza NM, Haydu LE, Wang XA, Hess KR, Kluger H, Glitza IC, Mahajan A, Welsh JW, Lin SH, Yu JB, Davies MA, Hwu P, Sulman EP, Brown PD, Chiang VLS, Li J. Stereotactic radiosurgery of early melanoma brain metastases after initiation of anti-CTLA-4 treatment is associated with improved intracranial control. Radiotherapy And Oncology 2017, 125: 80-88. PMID: 28916225, DOI: 10.1016/j.radonc.2017.08.009.Peer-Reviewed Original ResearchConceptsIntracranial disease controlNew brain metastasesIntracranial controlStereotactic radiosurgeryBrain metastasesOverall survivalDisease controlLymphocyte countMulti-institutional retrospective analysisYale-New Haven HospitalMD Anderson cohortMelanoma brain metastasesAbsolute lymphocyte countAntitumor immune responseImmune checkpoint blockadeMetastatic melanoma patientsComplete blood countTumor-specific antigensIndependent validation cohortMulti-institutional studyIpilimumab therapyMedian followLast doseCheckpoint blockadeIntracranial recurrenceNuclear IRF-1 expression as a mechanism to assess “Capability” to express PD-L1 and response to PD-1 therapy in metastatic melanoma
Smithy JW, Moore LM, Pelekanou V, Rehman J, Gaule P, Wong PF, Neumeister VM, Sznol M, Kluger HM, Rimm DL. Nuclear IRF-1 expression as a mechanism to assess “Capability” to express PD-L1 and response to PD-1 therapy in metastatic melanoma. Journal For ImmunoTherapy Of Cancer 2017, 5: 25. PMID: 28331615, PMCID: PMC5359951, DOI: 10.1186/s40425-017-0229-2.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAntibodies, MonoclonalAntibodies, Monoclonal, HumanizedB7-H1 AntigenBiomarkers, PharmacologicalDisease-Free SurvivalFemaleGene Expression Regulation, NeoplasticHumansImmunotherapyInterferon Regulatory Factor-1IpilimumabMaleMelanomaMiddle AgedNeoplasm MetastasisNeoplasms, Second PrimaryNivolumabProgrammed Cell Death 1 ReceptorConceptsProgression-free survivalObjective radiographic responsePD-L1 expressionPD-L1IRF-1 expressionMetastatic melanomaAnti-PD-1 therapyCombination ipilimumab/nivolumabHigh PD-L1 expressionAnti-PD-1 immunotherapyYale-New Haven HospitalIpilimumab/nivolumabPD-1 therapyPR/CRPre-treatment formalinRECIST v1.1 criteriaDeath ligand 1Valuable predictive biomarkerMajor unmet needNew Haven HospitalInterferon regulatory factor 1Combination ipilimumabProgressive diseaseRadiographic responseComplete response