2019
Perilesional edema in brain metastases: potential causes and implications for treatment with immune therapy
Tran TT, Mahajan A, Chiang VL, Goldberg SB, Nguyen DX, Jilaveanu LB, Kluger HM. Perilesional edema in brain metastases: potential causes and implications for treatment with immune therapy. Journal For ImmunoTherapy Of Cancer 2019, 7: 200. PMID: 31362777, PMCID: PMC6668163, DOI: 10.1186/s40425-019-0684-z.Peer-Reviewed Original ResearchMeSH KeywordsAdministration, IntravenousAntibodies, Monoclonal, HumanizedAntigens, CD34Antineoplastic Agents, ImmunologicalBlood-Brain BarrierBrain EdemaBrain NeoplasmsCarcinoma, Non-Small-Cell LungClinical Trials, Phase II as TopicDrug Administration ScheduleHumansLung NeoplasmsMelanomaRetrospective StudiesTight JunctionsTreatment OutcomeTumor Cells, CulturedConceptsMelanoma brain metastasesBrain metastasesPerilesional edemaVessel densityEdema volumeSensitive tumorsBlood-brain barrier model systemNon-small cell lungTight junction resistancePhase II clinical trialSignificant perilesional edemaUntreated brain metastasesBlood-brain barrierPre-clinical modelsDegree of edemaTumor mass effectPotential causesMelanoma brainShort-term cultureExtracranial metastasesImmune therapyMelanoma patientsSignificant morbidityCell lungLarge tumors
2017
Nivolumab Plus Ipilimumab in Patients With Advanced Melanoma: Updated Survival, Response, and Safety Data in a Phase I Dose-Escalation Study
Callahan MK, Kluger H, Postow MA, Segal NH, Lesokhin A, Atkins MB, Kirkwood JM, Krishnan S, Bhore R, Horak C, Wolchok JD, Sznol M. Nivolumab Plus Ipilimumab in Patients With Advanced Melanoma: Updated Survival, Response, and Safety Data in a Phase I Dose-Escalation Study. Journal Of Clinical Oncology 2017, 36: jco.2017.72.285. PMID: 29040030, PMCID: PMC5946731, DOI: 10.1200/jco.2017.72.2850.Peer-Reviewed Original ResearchConceptsPhase I dose-escalation studyTreatment-related adverse eventsI dose-escalation studyDose-escalation studyAdvanced melanomaOverall survivalAdverse eventsOS ratesClinical activityGrade 3Common grade 3Doses of nivolumabDurable clinical activityModified WHO criteriaNivolumab Plus IpilimumabTreatment-related deathsUntreated advanced melanomaImmune checkpoint inhibitorsMedian overall survivalObjective response rateLong-term followSubsequent clinical developmentConcurrent nivolumabCheckpoint inhibitorsExpansion cohort
2016
Phase I study of safety and tolerability of sunitinib in combination with sirolimus in patients with refractory solid malignancies and determination of VEGF (VEGF-A) and soluble VEGF-R2 (sVEGFR2) in plasma
Li J, Kluger H, Devine L, Lee JJ, Kelly WK, Rink L, Saif MW. Phase I study of safety and tolerability of sunitinib in combination with sirolimus in patients with refractory solid malignancies and determination of VEGF (VEGF-A) and soluble VEGF-R2 (sVEGFR2) in plasma. Cancer Chemotherapy And Pharmacology 2016, 77: 1193-1200. PMID: 27103123, DOI: 10.1007/s00280-016-3033-7.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAntineoplastic Combined Chemotherapy ProtocolsDose-Response Relationship, DrugDrug Administration ScheduleFemaleHumansIndolesMaleMaximum Tolerated DoseMiddle AgedNeoplasmsPyrrolesSirolimusSunitinibTOR Serine-Threonine KinasesVascular Endothelial Growth Factor AVascular Endothelial Growth Factor Receptor-2Young AdultConceptsRenal cell carcinomaComplete responseFourth cohortVEGF productionOral small-molecule inhibitorApparent pharmacokinetic interactionMedian age 57Prior systemic therapyRefractory solid malignanciesResidual renal massTolerability of sunitinibHand-foot syndromeHalf of patientsLymph node dissectionCombination of sunitinibPhase 1 studyDose of sunitinibOral mTOR inhibitorDose/scheduleUnknown compensatory mechanismsCycle 1Multiple receptor tyrosine kinasesAnti-tumor activityEpithelial growth factor receptor (EGFR) signalingTumor cell proliferationPD-1 Blockade with Pembrolizumab in Advanced Merkel-Cell Carcinoma
Nghiem PT, Bhatia S, Lipson EJ, Kudchadkar RR, Miller NJ, Annamalai L, Berry S, Chartash EK, Daud A, Fling SP, Friedlander PA, Kluger HM, Kohrt HE, Lundgren L, Margolin K, Mitchell A, Olencki T, Pardoll DM, Reddy SA, Shantha EM, Sharfman WH, Sharon E, Shemanski LR, Shinohara MM, Sunshine JC, Taube JM, Thompson JA, Townson SM, Yearley JH, Topalian SL, Cheever MA. PD-1 Blockade with Pembrolizumab in Advanced Merkel-Cell Carcinoma. New England Journal Of Medicine 2016, 374: 2542-2552. PMID: 27093365, PMCID: PMC4927341, DOI: 10.1056/nejmoa1603702.Peer-Reviewed Original ResearchConceptsAdvanced Merkel cell carcinomaMerkel cell carcinomaObjective response rateVirus-positive tumorsVirus-negative tumorsResponse rateDrug-related grade 3MCPyV-specific T cellsDose of pembrolizumabImmune inhibitory pathwaysPrevious systemic therapyTumor viral statusPD-1 blockadePrimary end pointFirst-line therapyProgression-free survivalResponse Evaluation CriteriaAggressive skin cancerMCPyV-positive tumorsMerkel cell polyomavirusAdverse eventsPartial responseSystemic therapyComplete responsePD-1
2014
Phase I/II Study of the Antibody-Drug Conjugate Glembatumumab Vedotin in Patients With Advanced Melanoma
Ott PA, Hamid O, Pavlick AC, Kluger H, Kim KB, Boasberg PD, Simantov R, Crowley E, Green JA, Hawthorne T, Davis TA, Sznol M, Hwu P. Phase I/II Study of the Antibody-Drug Conjugate Glembatumumab Vedotin in Patients With Advanced Melanoma. Journal Of Clinical Oncology 2014, 32: 3659-3666. PMID: 25267741, PMCID: PMC4879709, DOI: 10.1200/jco.2013.54.8115.Peer-Reviewed Original ResearchConceptsMaximum-tolerated doseObjective response rateGreater objective response rateGlembatumumab vedotinAdvanced melanomaGrade 3/4 treatment-related toxicitiesHuman immunoglobulin G2 monoclonal antibodyPhase I/II studyPhase II expansion cohortPromising objective response ratesEnd pointTreatment-related deathsPrimary end pointSecondary end pointsTreatment-related toxicityProgression-free survivalPhase II expansionMonomethyl auristatin E.Stable diseaseExpansion cohortII studyPartial responseDose escalationMore patientsFrequent dosing
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 ResearchMeSH KeywordsAntibodies, MonoclonalAntigens, CDClinical Trials as TopicColitisCTLA-4 AntigenDiarrheaDrug Administration ScheduleHumansImmunotherapyIpilimumabMelanomaConceptsMetastatic 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
2008
Toxicity and Activity of a Twice Daily High-dose Bolus Interleukin 2 Regimen in Patients With Metastatic Melanoma and Metastatic Renal Cell Cancer
Acquavella N, Kluger H, Rhee J, Farber L, Tara H, Ariyan S, Narayan D, Kelly W, Sznol M. Toxicity and Activity of a Twice Daily High-dose Bolus Interleukin 2 Regimen in Patients With Metastatic Melanoma and Metastatic Renal Cell Cancer. Journal Of Immunotherapy 2008, 31: 569-576. PMID: 18528297, DOI: 10.1097/cji.0b013e318177a4ba.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAntigens, CDCarcinoma, Renal CellCTLA-4 AntigenDrug Administration ScheduleFemaleHumansInterleukin-2Kidney NeoplasmsMaleMelanomaMiddle AgedConceptsIL-2 regimenMetastatic melanomaNormal saline fluid bolusesMetastatic renal cell cancerNew immune modulatorsTreatment-related deathsObjective response ratePercent of patientsRetrospective chart reviewSubset of patientsIL-2 dosesIntensive care unitRenal cell cancerRenal cancer patientsSubstantial acute toxicityDevelopment of combinationsChart reviewCare unitCell cancerMelanoma patientsOncology wardFluid bolusCancer patientsImmune modulatorsMedian number