2024
Causes of death and patterns of metastatic disease at the end of life for patients with advanced melanoma in the immunotherapy era.
Lee D, Yang A, McNamara M, Kluger H, Tran T, Olino K, Clune J, Sznol M, Ishizuka J. Causes of death and patterns of metastatic disease at the end of life for patients with advanced melanoma in the immunotherapy era. Journal Of Clinical Oncology 2024, 42: e21522-e21522. DOI: 10.1200/jco.2024.42.16_suppl.e21522.Peer-Reviewed Original ResearchImmune checkpoint inhibitorsYale Cancer CenterAdvanced melanomaMetastatic diseaseMetastatic melanomaRespiratory failureSite of metastatic diseasePattern of metastatic diseaseDied of respiratory failureAnti-CTLA4 treatmentRetrospective observational cohort studyAnti-PD1 therapyDistant lymph nodesPatients aged >Site of diseaseSurvival of patientsObservational cohort studyMulti-system involvementDiagnosis to deathImmunotherapy eraAnti-PD1Checkpoint inhibitorsInstitutional review boardMetastatic sitesMetastatic diagnosis
2023
Peripheral blood immune cell and cytokine profiling of patients receiving corticosteroids for immune checkpoint inhibitor-related adverse events: Steroid dose and duration.
Merkin R, Schoenfeld D, Djureinovic D, Austin M, Wang M, Qu R, Zhang L, Mann J, Wei W, Sun L, Aizenbud L, Destina J, Kluger H. Peripheral blood immune cell and cytokine profiling of patients receiving corticosteroids for immune checkpoint inhibitor-related adverse events: Steroid dose and duration. Journal Of Clinical Oncology 2023, 41: e14694-e14694. DOI: 10.1200/jco.2023.41.16_suppl.e14694.Peer-Reviewed Original ResearchImmune-related adverse eventsImmune checkpoint inhibitorsSevere immune-related adverse eventsPeripheral blood immune cellsBlood immune cellsSteroid therapyDose levelsSteroid taperAdverse eventsIL-6Immune cellsImmune checkpoint inhibitor-related adverse eventsSeverity of irAEsMultiple immune-related adverse eventsAnti-PD-1 therapyT effector memory cellsPeripheral blood mononuclear cellsYale Cancer CenterSerum cytokine concentrationsEffector memory cellsPathogenic T cellsBlood mononuclear cellsConcentrations of TNFαBiomarkers of responseT cell subtypes
2022
Immune Checkpoint Inhibitor-Induced Hypophysitis and Patterns of Loss of Pituitary Function
Jessel S, Weiss SA, Austin M, Mahajan A, Etts K, Zhang L, Aizenbud L, Perdigoto AL, Hurwitz M, Sznol M, Herold KC, Kluger HM. Immune Checkpoint Inhibitor-Induced Hypophysitis and Patterns of Loss of Pituitary Function. Frontiers In Oncology 2022, 12: 836859. PMID: 35350573, PMCID: PMC8958012, DOI: 10.3389/fonc.2022.836859.Peer-Reviewed Original ResearchImmune checkpoint inhibitorsRenal cell carcinomaCombination immune checkpoint inhibitorsCell carcinomaClinical experienceSelect casesIncidence of hypophysitisInstitution's clinical experienceYale Cancer CenterObjective response rateAdrenal axis hormonesFree testosterone levelsMerkel cell carcinomaHigh rateMultiple tumor typesCheckpoint inhibitorsPituitary axesReal-world practiceFree testosteroneMedian timeMelanoma patientsOverall incidencePituitary functionTreatment delayAxis hormones
2020
Pembrolizumab for management of patients with NSCLC and brain metastases: long-term results and biomarker analysis from a non-randomised, open-label, phase 2 trial
Goldberg SB, Schalper KA, Gettinger SN, Mahajan A, Herbst RS, Chiang AC, Lilenbaum R, Wilson FH, Omay SB, Yu JB, Jilaveanu L, Tran T, Pavlik K, Rowen E, Gerrish H, Komlo A, Gupta R, Wyatt H, Ribeiro M, Kluger Y, Zhou G, Wei W, Chiang VL, Kluger HM. Pembrolizumab for management of patients with NSCLC and brain metastases: long-term results and biomarker analysis from a non-randomised, open-label, phase 2 trial. The Lancet Oncology 2020, 21: 655-663. PMID: 32251621, PMCID: PMC7380514, DOI: 10.1016/s1470-2045(20)30111-x.Peer-Reviewed Original ResearchConceptsBrain metastasis responseYale Cancer CenterPD-L1 expressionPhase 2 trialUntreated brain metastasesBrain metastasesAdrenal insufficiencyAdverse eventsMetastasis responseCNS diseaseCancer CenterCohort 2Cohort 1Eastern Cooperative Oncology Group performance statusTreatment-related serious adverse eventsModified Response Evaluation CriteriaStage IV NSCLCTreatment-related deathsAcute kidney injuryPD-1 blockadeSerious adverse eventsSolid Tumors criteriaPhase 2 studyProportion of patientsResponse Evaluation Criteria
2019
Functional profile and clinical significance of major tumor infiltrating lymphocyte subsets in lung cancer-associated brain metastases.
Lu B, Gupta R, Stewart T, Kluger H, Jilaveanu L, Schalper K, Goldberg S. Functional profile and clinical significance of major tumor infiltrating lymphocyte subsets in lung cancer-associated brain metastases. Journal Of Clinical Oncology 2019, 37: 2066-2066. DOI: 10.1200/jco.2019.37.15_suppl.2066.Peer-Reviewed Original ResearchPrimary lung tumorsMajor T cell subsetsMultiplexed quantitative immunofluorescenceT cell subsetsExtracranial metastasesT cellsLung tumorsBrain metastasesQuantitative immunofluorescenceAdaptive anti-tumor responsesLow T cell infiltrationMajor clinicopathologic variablesYale Cancer CenterAdaptive immune cellsRegulatory T cellsT cell infiltrationAnti-tumor responseLonger overall survivalOptimal treatment strategyLung cancer patientsKi-67 levelsLung cancer histologyLymphocyte subsetsOverall survivalPrimary malignancy
2016
Pembrolizumab for patients with melanoma or non-small-cell lung cancer and untreated brain metastases: early analysis of a non-randomised, open-label, phase 2 trial
Goldberg SB, Gettinger SN, Mahajan A, Chiang AC, Herbst RS, Sznol M, Tsiouris AJ, Cohen J, Vortmeyer A, Jilaveanu L, Yu J, Hegde U, Speaker S, Madura M, Ralabate A, Rivera A, Rowen E, Gerrish H, Yao X, Chiang V, Kluger HM. Pembrolizumab for patients with melanoma or non-small-cell lung cancer and untreated brain metastases: early analysis of a non-randomised, open-label, phase 2 trial. The Lancet Oncology 2016, 17: 976-983. PMID: 27267608, PMCID: PMC5526047, DOI: 10.1016/s1470-2045(16)30053-5.Peer-Reviewed Original ResearchConceptsProgressive brain metastasesUntreated brain metastasesBrain metastasis responseYale Cancer CenterBrain metastasesPhase 2 trialCell lung cancerAdverse eventsMetastasis responseCancer CenterLung cancerMelanoma cohortGrade 3 colitisGrade 3 fatigueGrade 3 pneumonitisPD-1 axisAcute kidney injuryNeurological adverse eventsPD-1 inhibitorsAcceptable safety profilePD-L1 expressionSystemic immunotherapyKidney injuryPrimary endpointNSCLC cohort
2014
MEK 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