2023
ScRNA-seq defines dynamic T-cell subsets in longitudinal colon and peripheral blood samples in immune checkpoint inhibitor-induced colitis
Mann J, Lucca L, Austin M, Merkin R, Robert M, Al Bawardy B, Raddassi K, Aizenbud L, Joshi N, Hafler D, Abraham C, Herold K, Kluger H. ScRNA-seq defines dynamic T-cell subsets in longitudinal colon and peripheral blood samples in immune checkpoint inhibitor-induced colitis. Journal For ImmunoTherapy Of Cancer 2023, 11: e007358. PMID: 37586769, PMCID: PMC10432652, DOI: 10.1136/jitc-2023-007358.Peer-Reviewed Original ResearchConceptsImmune checkpoint inhibitorsT cell subsetsCheckpoint inhibitorsImmune environmentImmune checkpoint inhibitor-induced colitisCheckpoint inhibitor-induced colitisPeripheral immune environmentsStages of colitisTreatment of colitisMerkel cell carcinomaT cell populationsPeripheral blood samplesCourse of progressionT cell receptorMultiple tumor typesAlternative cancer therapyCommon toxicitiesICI colitisTreatment discontinuationAdverse eventsBiologic therapyImmune suppressionCell carcinomaColitisBlood samplesCase report: Metastatic Merkel cell carcinoma presenting seven years after loco-regional disease resection of primary tumor with interval in-transit and nodal metastases
Rusheen J, Clune J, Ariyan S, Baumann R, Kluger H, Olino K, Weiss S. Case report: Metastatic Merkel cell carcinoma presenting seven years after loco-regional disease resection of primary tumor with interval in-transit and nodal metastases. Frontiers In Oncology 2023, 13: 1217816. PMID: 37476373, PMCID: PMC10354444, DOI: 10.3389/fonc.2023.1217816.Peer-Reviewed Case Reports and Technical NotesMerkel cell carcinomaDuration of surveillanceLate recurrenceCell carcinomaMetastatic Merkel cell carcinomaPrimary Merkel cell carcinomaMetastases 15 monthsSuch late recurrencesPredictors of recurrenceNodal recurrenceDefinitive therapyFirst recurrenceDisease resectionNodal metastasisPhysical examinationRare tumorPrimary diagnosisPrimary tumorRisk factorsHigh riskNational guidelinesRecurrenceOptimal durationPatientsCarcinoma
2022
Society for Immunotherapy of Cancer (SITC) clinical practice guideline on immunotherapy for the treatment of nonmelanoma skin cancer
Silk AW, Barker CA, Bhatia S, Bollin KB, Chandra S, Eroglu Z, Gastman BR, Kendra KL, Kluger H, Lipson EJ, Madden K, Miller DM, Nghiem P, Pavlick AC, Puzanov I, Rabinowits G, Ruiz ES, Sondak VK, Tavss EA, Tetzlaff MT, Brownell I. Society for Immunotherapy of Cancer (SITC) clinical practice guideline on immunotherapy for the treatment of nonmelanoma skin cancer. Journal For ImmunoTherapy Of Cancer 2022, 10: e004434. PMID: 35902131, PMCID: PMC9341183, DOI: 10.1136/jitc-2021-004434.Peer-Reviewed Original ResearchConceptsNonmelanoma skin cancerClinical practice guidelinesImmune checkpoint inhibitorsCutaneous squamous cell carcinomaMerkel cell carcinomaBasal cell carcinomaCell carcinomaPractice guidelinesSkin cancerCancer clinical practice guidelinesCancer care professionalsManagement of toxicitiesSpecial patient populationsSquamous cell carcinomaImmunotherapy of cancerConsensus-based recommendationsOwn clinical experienceRoutine clinical useCheckpoint inhibitorsMetastatic diseasePatient selectionPatients' qualityImmunotherapeutic treatmentPatient populationAggressive subtypeImmune 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
2021
Three-year survival, correlates and salvage therapies in patients receiving first-line pembrolizumab for advanced Merkel cell carcinoma
Nghiem P, Bhatia S, Lipson EJ, Sharfman WH, Kudchadkar RR, Brohl AS, Friedlander PA, Daud A, Kluger HM, Reddy SA, Boulmay BC, Riker A, Burgess MA, Hanks BA, Olencki T, Kendra K, Church C, Akaike T, Ramchurren N, Shinohara MM, Salim B, Taube JM, Jensen E, Kalabis M, Fling SP, Moreno B, Sharon E, Cheever MA, Topalian SL. Three-year survival, correlates and salvage therapies in patients receiving first-line pembrolizumab for advanced Merkel cell carcinoma. Journal For ImmunoTherapy Of Cancer 2021, 9: e002478. PMID: 33879601, PMCID: PMC8061836, DOI: 10.1136/jitc-2021-002478.Peer-Reviewed Original ResearchConceptsProgression-free survivalMerkel cell carcinomaSalvage therapyStable diseaseCell carcinomaBaseline Eastern Cooperative Oncology Group performance statusEastern Cooperative Oncology Group performance statusAnti-programmed death-1 therapyCell death-1 pathway inhibitorsDeath-1 pathway inhibitorsDurable progression-free survivalFirst-line pembrolizumab therapyMedian progression-free survivalMulticenter phase II trialRefractory Merkel cell carcinomaTumor progressionAdvanced Merkel cell carcinomaMedian response durationFirst-line pembrolizumabPhase II trialProportion of patientsInitial disease progressionThree-year survivalDurable tumor regressionOverall response rateAssessment of Age, Period, and Birth Cohort Effects and Trends in Merkel Cell Carcinoma Incidence in the United States
Jacobs D, Huang H, Olino K, Weiss S, Kluger H, Judson BL, Zhang Y. Assessment of Age, Period, and Birth Cohort Effects and Trends in Merkel Cell Carcinoma Incidence in the United States. JAMA Dermatology 2021, 157: 59-65. PMID: 33146688, PMCID: PMC7643047, DOI: 10.1001/jamadermatol.2020.4102.Peer-Reviewed Original ResearchConceptsMerkel cell carcinomaBirth cohort effectsCell carcinomaIncidence rateCalendar periodBirth cohortPatient ageNew casesCohort effectsEnd Results Program databaseCross-sectional retrospective studyLongitudinal cohort studyHigh incidence rateAge-adjusted ratesRisk factor exposureRecent birth cohortsCohort studyCarcinoma incidenceRetrospective studyNeuroendocrine cancerAge effectsProgram databaseCohort analysisMAIN OUTCOMECarcinoma
2020
Primary Treatment Selection for Clinically Node-Negative Merkel Cell Carcinoma of the Head and Neck
Jacobs D, Olino K, Park HS, Clune J, Cheraghlou S, Girardi M, Burtness B, Kluger H, Judson BL. Primary Treatment Selection for Clinically Node-Negative Merkel Cell Carcinoma of the Head and Neck. Otolaryngology 2020, 164: 1214-1221. PMID: 33079010, DOI: 10.1177/0194599820967001.Peer-Reviewed Original ResearchConceptsNode-negative Merkel cell carcinomaLymph node evaluationImproved overall survivalPrimary tumor excisionMerkel cell carcinomaCase volumeOverall survivalSurgical managementCell carcinomaTumor excisionTreatment selectionNode evaluationCox proportional hazards regressionGuideline-recommended carePrimary treatment selectionNational Cancer DatabaseNode-negative diseasePercentage of patientsRetrospective cohort analysisInitial surgical managementKaplan-Meier analysisWide local excisionProportional hazards regressionRates of receiptInitial management
2019
Durable Tumor Regression and Overall Survival in Patients With Advanced Merkel Cell Carcinoma Receiving Pembrolizumab as First-Line Therapy
Nghiem P, Bhatia S, Lipson EJ, Sharfman WH, Kudchadkar RR, Brohl AS, Friedlander PA, Daud A, Kluger HM, Reddy SA, Boulmay BC, Riker AI, Burgess MA, Hanks BA, Olencki T, Margolin K, Lundgren LM, Soni A, Ramchurren N, Church C, Park SY, Shinohara MM, Salim B, Taube JM, Bird SR, Ibrahim N, Fling SP, Moreno B, Sharon E, Cheever MA, Topalian SL. Durable Tumor Regression and Overall Survival in Patients With Advanced Merkel Cell Carcinoma Receiving Pembrolizumab as First-Line Therapy. Journal Of Clinical Oncology 2019, 37: jco.18.01896. PMID: 30726175, PMCID: PMC6424137, DOI: 10.1200/jco.18.01896.Peer-Reviewed Original ResearchMeSH KeywordsAgedAged, 80 and overAntibodies, Monoclonal, HumanizedAntineoplastic Agents, ImmunologicalB7-H1 AntigenCarcinoma, Merkel CellFemaleFollow-Up StudiesHumansHypothyroidismMaleMiddle AgedPneumoniaProgression-Free SurvivalRemission InductionResponse Evaluation Criteria in Solid TumorsSkin NeoplasmsConceptsObjective response rateProgression-free survivalMerkel cell carcinomaAdvanced MCCAnti-programmed cell death-1 therapyCell death-1 pathway inhibitorsGreater treatment-related adverse eventsDeath-1 pathway inhibitorsMulticenter phase II trialTreatment-related adverse eventsAdvanced Merkel cell carcinomaDurable tumor controlManageable safety profileMedian OS timeMedian response durationSolid Tumors v1.1Treatment-related deathsTumor viral statusDate of patientsFirst-line chemotherapyFirst-line therapyMedian PFS timePhase II trialResponse Evaluation CriteriaOverall survival data
2018
Merkel cell polyomavirus-specific immune responses in patients with Merkel cell carcinoma receiving anti-PD-1 therapy
Miller NJ, Church CD, Fling SP, Kulikauskas R, Ramchurren N, Shinohara MM, Kluger HM, Bhatia S, Lundgren L, Cheever MA, Topalian SL, Nghiem P. Merkel cell polyomavirus-specific immune responses in patients with Merkel cell carcinoma receiving anti-PD-1 therapy. Journal For ImmunoTherapy Of Cancer 2018, 6: 131. PMID: 30482247, PMCID: PMC6258401, DOI: 10.1186/s40425-018-0450-7.Peer-Reviewed Original ResearchMeSH KeywordsAntineoplastic Agents, ImmunologicalBiomarkers, TumorB-LymphocytesCarcinoma, Merkel CellHumansImmunomodulationLymphocyte ActivationMerkel cell polyomavirusMolecular Targeted TherapyPolyomavirus InfectionsProgrammed Cell Death 1 ReceptorReceptors, Antigen, T-CellT-Cell Antigen Receptor SpecificityT-LymphocytesTreatment OutcomeTumor Virus InfectionsConceptsAnti-PD-1 therapyPeripheral blood mononuclear cellsB cell responsesCell responsesCell carcinomaT cellsDiverse T-cell responsePD-1 blockade therapyPre-treatment tumor biopsiesVirus-specific T cellsT-cell receptor clonalityVP-MCCCancer-specific immunityIntratumoral TCR repertoirePD-1 blockadeTumor-specific immunityT cell responsesBlood mononuclear cellsMerkel cell carcinomaAggressive skin cancerBackgroundMerkel cell carcinomaVirus-negative tumorsMerkel cell polyomavirusPresence of antigenMethodsImmune responsesDurable tumor regression and overall survival (OS) in patients with advanced Merkel cell carcinoma (aMCC) receiving pembrolizumab as first-line therapy.
Nghiem P, Bhatia S, Lipson E, Sharfman W, Kudchadkar R, Friedlander P, Brohl A, Daud A, Kluger H, Reddy S, Burgess M, Hanks B, Olencki T, Boulmay B, Lundgren L, Ramchurren N, Homet Moreno B, Sharon E, Cheever M, Topalian S. Durable tumor regression and overall survival (OS) in patients with advanced Merkel cell carcinoma (aMCC) receiving pembrolizumab as first-line therapy. Journal Of Clinical Oncology 2018, 36: 9506-9506. DOI: 10.1200/jco.2018.36.15_suppl.9506.Peer-Reviewed Original Research
2016
PD-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