2024
GP100 expression is variable in intensity in melanoma
Mann J, Hasson N, Su D, Adeniran A, Smalley K, Djureinovic D, Jilaveanu L, Schoenfeld D, Kluger H. GP100 expression is variable in intensity in melanoma. Cancer Immunology, Immunotherapy 2024, 73: 191. PMID: 39105816, PMCID: PMC11303354, DOI: 10.1007/s00262-024-03776-5.Peer-Reviewed Original ResearchConceptsGp100 expressionCutaneous melanomaTreatment of cutaneous melanomaAdvanced cutaneous melanomaT-cell engagersImprove patient selectionMetastatic melanomaUveal melanomaMetastatic samplesPatient selectionClinical trialsMelanomaQuantitative immunofluorescence methodGp100Improve outcomesImmunofluorescence methodTherapeutic intentDrugCellular productsExpressionTebentafuspImmunohistochemistryMelanocortin-1 Receptor Expression as a Marker of Progression in Melanoma
Su D, Djureinovic D, Schoenfeld D, Marquez-Nostra B, Olino K, Jilaveanu L, Kluger H. Melanocortin-1 Receptor Expression as a Marker of Progression in Melanoma. JCO Precision Oncology 2024, 8: e2300702. PMID: 38662983, PMCID: PMC11513442, DOI: 10.1200/po.23.00702.Peer-Reviewed Original ResearchConceptsMC1R expressionMelanoma progressionAssociated with shorter survivalStages of melanoma progressionCases of benign neviChronic sun exposureMarkers of progressionHuman melanoma tissuesBreslow thicknessMelanocortin-1Metastatic melanomaOverall survivalPrimary melanomaMetastatic tumorsMelanoma cohortReceptor expressionPredictive biomarkersAggressive melanomaPrimary lesionTissue microarrayShorter survivalMale sexQuantitative immunofluorescenceBenign neviClinical trials
2023
Leptomeningeal disease in melanoma: An update on the developments in pathophysiology and clinical care
Smalley I, Boire A, Brastianos P, Kluger H, Hernando‐Monge E, Forsyth P, Ahmed K, Smalley K, Ferguson S, Davies M, Oliva I. Leptomeningeal disease in melanoma: An update on the developments in pathophysiology and clinical care. Pigment Cell & Melanoma Research 2023, 37: 51-67. PMID: 37622466, DOI: 10.1111/pcmr.13116.Peer-Reviewed Original Research
2022
Melanoma central nervous system metastases: An update to approaches, challenges, and opportunities
Karz A, Dimitrova M, Kleffman K, Alvarez‐Breckenridge C, Atkins MB, Boire A, Bosenberg M, Brastianos P, Cahill DP, Chen Q, Ferguson S, Forsyth P, Oliva I, Goldberg SB, Holmen SL, Knisely JPS, Merlino G, Nguyen DX, Pacold ME, Perez‐Guijarro E, Smalley KSM, Tawbi HA, Wen PY, Davies MA, Kluger HM, Mehnert JM, Hernando E. Melanoma central nervous system metastases: An update to approaches, challenges, and opportunities. Pigment Cell & Melanoma Research 2022, 35: 554-572. PMID: 35912544, PMCID: PMC10171356, DOI: 10.1111/pcmr.13059.Peer-Reviewed Original ResearchConceptsMelanoma brain metastasesMBM patientsBrain metastasesCheckpoint inhibitor trialsCommon brain malignancyMelanoma Research FoundationDedicated clinical trialsRole of astrocytesNovel treatment approachesImmunotherapy trialsInhibitor trialsBrain malignanciesClinical trialsPatient outcomesBrain microenvironmentTreatment approachesPatient advocatesPatientsTrialsTherapeutic purposesMetabolic adaptationMetastasisCurrent standardTherapyRecent reportsAssociation Between Food and Drug Administration Approval and Disparities in Immunotherapy Use Among Patients With Cancer in the US
Ermer T, Canavan ME, Maduka RC, Li AX, Salazar MC, Kaminski MF, Pichert MD, Zhan PL, Mase V, Kluger H, Boffa DJ. Association Between Food and Drug Administration Approval and Disparities in Immunotherapy Use Among Patients With Cancer in the US. JAMA Network Open 2022, 5: e2219535. PMID: 35771575, PMCID: PMC9247736, DOI: 10.1001/jamanetworkopen.2022.19535.Peer-Reviewed Original ResearchConceptsNon-small cell lung cancerRenal cell carcinomaUse of immunotherapyFDA approvalImmunotherapy useCohort studyClinical trialsNovel therapiesStage IV non-small cell lung cancerMultivariable logistic regression modelingFirst checkpoint inhibitorCheckpoint inhibitor therapyNational Cancer DatabasePatients 20 yearsCell lung cancerSocioeconomic strataTreatment of patientsDrug Administration approvalLife-saving treatmentReceipt of immunotherapyLogistic regression modelingSocioeconomic characteristicsImmunotherapy administrationCheckpoint inhibitorsPatient characteristics
2021
Agonistic CD40 Antibodies in Cancer Treatment
Djureinovic D, Wang M, Kluger HM. Agonistic CD40 Antibodies in Cancer Treatment. Cancers 2021, 13: 1302. PMID: 33804039, PMCID: PMC8000216, DOI: 10.3390/cancers13061302.Peer-Reviewed Original ResearchAgonistic CD40 antibodyCD40 antibodyDendritic cellsAntigen presentationClinical developmentEarly phase clinical trialsAgonist CD40 antibodyActivation of CD8Pro-inflammatory effectsAntigen-presenting cellsT cell functionRenal cell carcinomaAnti-tumor effectsPhase clinical trialsAnti-tumor activityT cell activationCancer Genome AtlasSystemic therapyCell carcinomaCostimulatory moleculesCD40 expressionClinical trialsPancreatic adenocarcinomaPreclinical modelsT cellsAutomated digital TIL analysis (ADTA) adds prognostic value to standard assessment of depth and ulceration in primary melanoma
Moore MR, Friesner ID, Rizk EM, Fullerton BT, Mondal M, Trager MH, Mendelson K, Chikeka I, Kurc T, Gupta R, Rohr BR, Robinson EJ, Acs B, Chang R, Kluger H, Taback B, Geskin LJ, Horst B, Gardner K, Niedt G, Celebi JT, Gartrell-Corrado RD, Messina J, Ferringer T, Rimm DL, Saltz J, Wang J, Vanguri R, Saenger YM. Automated digital TIL analysis (ADTA) adds prognostic value to standard assessment of depth and ulceration in primary melanoma. Scientific Reports 2021, 11: 2809. PMID: 33531581, PMCID: PMC7854647, DOI: 10.1038/s41598-021-82305-1.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overBiopsyChemotherapy, AdjuvantClinical Decision-MakingDeep LearningFemaleFollow-Up StudiesHumansImage Processing, Computer-AssistedKaplan-Meier EstimateLymphocytes, Tumor-InfiltratingMaleMelanomaMiddle AgedNeoplasm StagingPatient SelectionPrognosisRetrospective StudiesRisk AssessmentROC CurveSkinSkin NeoplasmsYoung AdultConceptsTumor-infiltrating lymphocytesDisease-specific survivalEarly-stage melanomaOpen-source deep learningCutoff valueMultivariable Cox proportional hazards analysisCox proportional hazards analysisDeep learningLow-risk patientsProportional hazards analysisKaplan-Meier analysisAccurate prognostic biomarkersEosin imagesAccuracy of predictionAdjuvant therapyRisk patientsSpecific survivalPrognostic valueValidation cohortReceiver operating curvesTraining cohortTIL analysisClinical trialsPrimary melanomaPrognostic biomarker
2020
Melanoma brain metastases have lower T-cell content and microvessel density compared to matched extracranial metastases
Weiss SA, Zito C, Tran T, Heishima K, Neumeister V, McGuire J, Adeniran A, Kluger H, Jilaveanu LB. Melanoma brain metastases have lower T-cell content and microvessel density compared to matched extracranial metastases. Journal Of Neuro-Oncology 2020, 152: 15-25. PMID: 32974852, PMCID: PMC7910371, DOI: 10.1007/s11060-020-03619-0.Peer-Reviewed Original ResearchConceptsT-cell contentMelanoma brain metastasesPD-L1 expressionLower microvessel densityMicrovessel densityBrain metastasesExtracranial metastasesMacrophage contentB cellsProspective therapeutic clinical trialsTumor-infiltrating T cellsImmune-modulating drugsImmune cell subsetsTherapeutic clinical trialsExtracerebral metastasesHigh CD68Low CD3Low CD8Systemic therapyIntracerebral metastasesMetastatic sitesCell subsetsMetastatic melanomaImmune cellsClinical trialsSystemic Therapy for Brain Metastases: Melanoma
Weiss S, Kluger H. Systemic Therapy for Brain Metastases: Melanoma. 2020, 235-244. DOI: 10.1007/978-3-030-42958-4_16.Peer-Reviewed Original ResearchMelanoma brain metastasesIntracranial response ratesBrain metastasesClinical trialsResponse rateAnti-PD-1 monotherapyCentral nervous system metastasesExtracranial metastatic sitesNervous system metastasesSystemic therapy approachesMultiple clinical trialsSystemic therapySystemic treatmentAdvanced melanomaImmune checkpointsMetastatic sitesTherapeutic challengePatient survivalMetastatic melanomaExtracranial sitesStereotactic radiosurgeryMetastasisMutant BRAFSignificant causeMEK inhibitionDefining tumor resistance to PD-1 pathway blockade: recommendations from the first meeting of the SITC Immunotherapy Resistance Taskforce
Kluger HM, Tawbi HA, Ascierto ML, Bowden M, Callahan MK, Cha E, Chen HX, Drake CG, Feltquate DM, Ferris RL, Gulley JL, Gupta S, Humphrey RW, LaVallee TM, Le DT, Hubbard-Lucey VM, Papadimitrakopoulou VA, Postow MA, Rubin EH, Sharon E, Taube JM, Topalian SL, Zappasodi R, Sznol M, Sullivan RJ. Defining tumor resistance to PD-1 pathway blockade: recommendations from the first meeting of the SITC Immunotherapy Resistance Taskforce. Journal For ImmunoTherapy Of Cancer 2020, 8: e000398. PMID: 32238470, PMCID: PMC7174063, DOI: 10.1136/jitc-2019-000398.Peer-Reviewed Original ResearchConceptsCancer immunotherapyClinical definitionNew agentsPD-1/PD-L1 blockadePD-1 pathway blockadeConsensus clinical definitionPD-L1 blockadeDeath receptor-1Immunotherapy of cancerStandard of careClinical trial designTreatment discontinuationMechanisms of resistancePathway blockadeClinical trialsConfirmatory scanPrimary resistancePatient benefitSecondary resistanceTrial designTreatment approachesUnmet needReceptor 1Tumor resistancePattern of response
2019
Complications associated with immunotherapy for brain metastases.
Tran TT, Jilaveanu LB, Omuro A, Chiang VL, Huttner A, Kluger HM. Complications associated with immunotherapy for brain metastases. Current Opinion In Neurology 2019, 32: 907-916. PMID: 31577604, PMCID: PMC7398556, DOI: 10.1097/wco.0000000000000756.Peer-Reviewed Original ResearchConceptsBrain metastasesNeurologic toxicityImmune therapyPhase 2 clinical trialCheckpoint inhibitor therapyImmune checkpoint inhibitorsMultiple phase 2 clinical trialsTreatment-related morbidityBrain metastatic diseaseSymptomatic edemaCheckpoint inhibitorsAdverse eventsDurable responsesMedian survivalMetastatic diseaseInhibitor therapyMore patientsIntracranial activityPatient groupRadiation necrosisClinical trialsTherapy trialsMultidisciplinary teamMetastasisPatientsFrequent Use of Local Therapy Underscores Need for Multidisciplinary Care in the Management of Patients With Melanoma Brain Metastases Treated With PD-1 Inhibitors
Qian JM, Yu JB, Mahajan A, Goldberg SB, Kluger HM, Chiang VLS. Frequent Use of Local Therapy Underscores Need for Multidisciplinary Care in the Management of Patients With Melanoma Brain Metastases Treated With PD-1 Inhibitors. International Journal Of Radiation Oncology • Biology • Physics 2019, 105: 1113-1118. PMID: 31479702, DOI: 10.1016/j.ijrobp.2019.08.053.Peer-Reviewed Original ResearchConceptsBrain metastasesLocal therapyNeurologic safetyMelanoma patientsProspective phase 2 trialProgressive brain metastasesSerial brain imagingMelanoma brain metastasesPD-1 inhibitorsPhase 2 trialRapid disease progressionManagement of patientsNeurologic symptomsMultidisciplinary careTrial enrollmentCystic changesClinical trialsDisease progressionPatientsLesion sizeMetastasisMultidisciplinary teamTumor growthTherapyClinical decisionBrain Metastasis From Renal-Cell Carcinoma: An Institutional Study
Suarez-Sarmiento A, Nguyen KA, Syed JS, Nolte A, Ghabili K, Cheng M, Liu S, Chiang V, Kluger H, Hurwitz M, Shuch B. Brain Metastasis From Renal-Cell Carcinoma: An Institutional Study. Clinical Genitourinary Cancer 2019, 17: e1163-e1170. PMID: 31519468, DOI: 10.1016/j.clgc.2019.08.006.Peer-Reviewed Original ResearchConceptsRCC brain metastasesRecurrence-free survivalRenal cell carcinomaBrain metastasesOverall survivalClinical trialsAdvanced renal cell carcinomaCentral nervous system treatmentClear cell renal cell carcinomaMedian overall survivalSingle institution experienceGood local controlKaplan-Meier methodAggressive therapyCNS recurrenceTreatment eraCumulative incidenceExtracranial metastasesMetastatic diseaseSystemic therapyInitial presentationLocal therapyClinical symptomsRCC patientsCell carcinoma
2017
Comparing available criteria for measuring brain metastasis response to immunotherapy
Qian JM, Mahajan A, Yu JB, Tsiouris AJ, Goldberg SB, Kluger HM, Chiang VL. Comparing available criteria for measuring brain metastasis response to immunotherapy. Journal Of Neuro-Oncology 2017, 132: 479-485. PMID: 28275886, DOI: 10.1007/s11060-017-2398-8.Peer-Reviewed Original ResearchConceptsRECIST 1.1Brain lesionsBrain metastasesDurable responsesAdditional patientsNeuro-Oncology Working GroupBrain metastasis responseBrain metastasis patientsUntreated brain metastasesStandardized response criteriaBrain lesion sizeHigh-grade gliomasSimilar clinical trialsHigh-resolution MRIMetastasis patientsMetastasis responseOngoing trialsClinical trialsNovel therapiesResponse assessmentDiscordant casesLesion sizePatientsResponse rateLongest diameter
2016
The Treatment of Melanoma Brain Metastases
Kibbi N, Kluger H. The Treatment of Melanoma Brain Metastases. Current Oncology Reports 2016, 18: 73. PMID: 27822695, DOI: 10.1007/s11912-016-0555-4.Peer-Reviewed Original ResearchConceptsMelanoma brain metastasesBrain metastasesSystemic therapyClinical trialsAsymptomatic brain metastasesPrognosis of patientsUntreated brain metastasesPopulation of patientsOngoing clinical trialsCentral nervous systemMBM patientsCerebral edemaTreatment landscapeImproved survivalIntracranial metastasesMetastatic melanomaStereotactic radiosurgeryNew therapiesLocal modalitiesNervous systemPatientsDrug AdministrationRegistration trialsMetastasisEarly intervention
2014
Immunomodulatory activity of nivolumab in previously treated and untreated metastatic renal cell carcinoma (mRCC): Biomarker-based results from a randomized clinical trial.
Choueiri T, Fishman M, Escudier B, Kim J, Kluger H, Stadler W, Perez-Gracia J, McNeel D, Curti B, Harrison M, Plimack E, Appleman L, Fong L, Drake C, Cohen L, Srivastava S, Jure-Kunkel M, Hong Q, Kurland J, Sznol M. Immunomodulatory activity of nivolumab in previously treated and untreated metastatic renal cell carcinoma (mRCC): Biomarker-based results from a randomized clinical trial. Journal Of Clinical Oncology 2014, 32: 5012-5012. DOI: 10.1200/jco.2014.32.15_suppl.5012.Peer-Reviewed Original ResearchMEK targeting in N-RAS mutated metastatic melanoma
Thumar J, Shahbazian D, Aziz SA, Jilaveanu LB, Kluger HM. MEK targeting in N-RAS mutated metastatic melanoma. Molecular Cancer 2014, 13: 45. PMID: 24588908, PMCID: PMC3945937, DOI: 10.1186/1476-4598-13-45.Peer-Reviewed Original ResearchConceptsN-RASShort-term cultureMelanoma patientsMelanoma culturesYale Cancer CenterMetastatic melanoma patientsTime of presentationOngoing clinical trialsProtein kinase pathway activationN-RAS mutationsB-RafPan-RAF inhibitorTerm cultureKinase pathway activationConclusionsThe prognosisBrain metastasesClinical characteristicsMetastatic diseasePathologic dataWorse prognosisCancer CenterMetastatic melanomaClinical trialsMutant melanomaMelanoma cell cultures
2012
CD70 expression patterns in renal cell carcinoma
Jilaveanu LB, Sznol J, Aziz SA, Duchen D, Kluger HM, Camp RL. CD70 expression patterns in renal cell carcinoma. Human Pathology 2012, 43: 1394-1399. PMID: 22401771, PMCID: PMC3374042, DOI: 10.1016/j.humpath.2011.10.014.Peer-Reviewed Original ResearchConceptsRenal cell carcinomaCell carcinomaCD70 expressionPapillary tumorsHigh CD70 expressionExpression of CD70Clear cell tumorsNovel therapeutic agentsRenal cell carcinoma specimensPathologic variablesHistologic subtypePrognostic valueCell subsetsCell tumorsUnivariate analysisClinical trialsImmune escapeSitu protein expressionT lymphocytesClear cellsTissue microarrayCarcinoma specimensCD70Immunohistochemistry-based methodMultivariate analysis
2011
Characterization and targeting of phosphatidylinositol-3 kinase (PI3K) and mammalian target of rapamycin (mTOR) in renal cell cancer
Elfiky AA, Aziz SA, Conrad PJ, Siddiqui S, Hackl W, Maira M, Robert CL, Kluger HM. Characterization and targeting of phosphatidylinositol-3 kinase (PI3K) and mammalian target of rapamycin (mTOR) in renal cell cancer. Journal Of Translational Medicine 2011, 9: 133. PMID: 21834980, PMCID: PMC3173341, DOI: 10.1186/1479-5876-9-133.Peer-Reviewed Original ResearchMeSH KeywordsApoptosisAutomationBiomarkers, TumorCarcinoma, Renal CellCell Line, TumorChromonesDrug SynergismHumansImidazolesInhibitory Concentration 50Kidney NeoplasmsMolecular Targeted TherapyMorpholinesMultivariate AnalysisPhosphatidylinositol 3-KinasePhosphoinositide-3 Kinase InhibitorsProtein Kinase InhibitorsQuinolinesSirolimusTOR Serine-Threonine KinasesConceptsRenal cell carcinomaRCC cell linesNVP-BEZ235PI3KMTOR expressionMetastatic renal cell carcinomaPI3K subunitsHigh mTOR expressionAutomated Quantitative AnalysisRCC cell growthRenal cell cancerExpression of p85PI3K inhibitor LY294002Cell linesWarrants further investigationK inhibitor LY294002PI3K inhibitorsMulti-variable analysisCell cancerCell carcinomaClinical trialsSitu protein expressionNephrectomy casesTissue microarrayMTOR inhibitors
2010
Ipilimumab: a promising immunotherapy for melanoma.
Thumar JR, Kluger HM. Ipilimumab: a promising immunotherapy for melanoma. Oncology 2010, 24: 1280-8. PMID: 21294471.Peer-Reviewed Original ResearchConceptsMetastatic melanomaClinical trialsCytotoxic T-lymphocyte antigen-4Recent phase III trialsT-lymphocyte antigen-4Overall survival benefitPhase III trialsDrug-related toxicityAntibody-based targetingIII trialsSurvival benefitPromising immunotherapyAntigen-4Immune modulationTreatment responseTherapeutic benefitMelanomaIpilimumabTrialsImmunotherapyUnique challengesCancerClinicians