2023
A bedside to bench study of anti-PD-1, anti-CD40, and anti-CSF1R indicates that more is not necessarily better
Djureinovic D, Weiss S, Krykbaeva I, Qu R, Vathiotis I, Moutafi M, Zhang L, Perdigoto A, Wei W, Anderson G, Damsky W, Hurwitz M, Johnson B, Schoenfeld D, Mahajan A, Hsu F, Miller-Jensen K, Kluger Y, Sznol M, Kaech S, Bosenberg M, Jilaveanu L, Kluger H. A bedside to bench study of anti-PD-1, anti-CD40, and anti-CSF1R indicates that more is not necessarily better. Molecular Cancer 2023, 22: 182. PMID: 37964379, PMCID: PMC10644655, DOI: 10.1186/s12943-023-01884-x.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntibodies, MonoclonalHumansMelanomaMiceNivolumabReceptor Protein-Tyrosine KinasesConceptsStable diseasePartial responseMacrophage populationsThree-drug regimenUnconfirmed partial responsePhase I trialLimited treatment optionsMonocyte/macrophage populationNon-classical monocytesMurine melanoma modelTreatment-related changesResultsThirteen patientsWorse survivalI trialInflammatory tumorPatient populationTreatment optionsImmune cellsDisease progressionMurine studiesPreclinical modelsResistant melanomaAntigen presentationMurine modelCyTOF analysisA Phase II Trial of the CD40 Agonist Sotigalimab (APX005M) in Combination with Nivolumab in Subjects with Metastatic Melanoma with Disease Progression on Anti-PD-1
Weiss S, Sznol M, Shaheen M, Berciano-Guerrero M, Couselo E, Rodríguez-Abreu D, Boni V, Schuchter L, Gonzalez-Cao M, Arance A, Wei W, Ganti A, Hauke R, Berrocal A, Iannotti N, Hsu F, Kluger H. A Phase II Trial of the CD40 Agonist Sotigalimab (APX005M) in Combination with Nivolumab in Subjects with Metastatic Melanoma with Disease Progression on Anti-PD-1. Clinical Cancer Research 2023, 30: 74-81. PMID: 37535056, PMCID: PMC10767304, DOI: 10.1158/1078-0432.ccr-23-0475.Peer-Reviewed Original ResearchConceptsObjective response ratePhase II trialAdverse eventsPartial responseDisease progressionII trialGrade 3 adverse eventsAnti PD-1CD40 agonist antibodyElevated liver functionTreatment-related SAEsCommon adverse eventsActivation of CD40Subset of patientsFavorable safety profileAntigen presenting cellsStable diseaseMedian durationAdvanced melanomaAdditional patientsLiver functionSafety profileMetastatic melanomaPreclinical dataPresenting cellsSubsets 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 ResearchMeSH KeywordsB7-H1 AntigenHumansImmune Checkpoint InhibitorsIpilimumabMelanomaNivolumabTumor MicroenvironmentConceptsImmune 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 patterns
2022
FRACTION-RCC: nivolumab plus ipilimumab for advanced renal cell carcinoma after progression on immuno-oncology therapy
Choueiri T, Kluger H, George S, Tykodi S, Kuzel T, Perets R, Nair S, Procopio G, Carducci M, Castonguay V, Folefac E, Lee C, Hotte S, Miller W, Saggi S, Lee C, Desilva H, Bhagavatheeswaran P, Motzer R, Escudier B. FRACTION-RCC: nivolumab plus ipilimumab for advanced renal cell carcinoma after progression on immuno-oncology therapy. Journal For ImmunoTherapy Of Cancer 2022, 10: e005780. PMID: 36328377, PMCID: PMC9639138, DOI: 10.1136/jitc-2022-005780.Peer-Reviewed Original ResearchConceptsAdvanced renal cell carcinomaObjective response rateDuration of responseIO therapyImmuno-oncology therapiesRenal cell carcinomaOverall survivalCell carcinomaAnti-PD-1/PD-L1 therapyImmune-mediated adverse eventsMedian DORProgression-free survival ratesTreatment-related deathsManageable safety profileMedian overall survivalPD-L1 therapyDurable clinical benefitKarnofsky performance statusPrimary outcome measureHigh unmet needExploratory endpointsIpilimumab armPFS ratesStable diseaseAdverse eventsAutoimmune retinopathy with associated anti-retinal antibodies as a potential immune-related adverse event associated with immunotherapy in patients with advanced cutaneous melanoma: case series and systematic review
Heng JS, Kim JM, Jones DK, Stoessel KM, Weiss SA, Sznol M, Kluger HM, Walter SD, Silverstein NA, Pointdujour-Lim R. Autoimmune retinopathy with associated anti-retinal antibodies as a potential immune-related adverse event associated with immunotherapy in patients with advanced cutaneous melanoma: case series and systematic review. BMJ Open Ophthalmology 2022, 7: e000889. PMID: 35047671, PMCID: PMC8724805, DOI: 10.1136/bmjophth-2021-000889.Peer-Reviewed Original ResearchConceptsAdvanced cutaneous melanomaAnti-retinal antibodiesImmune-related adverse eventsAutoimmune retinopathyCutaneous melanomaNivolumab immunotherapySystematic reviewAdverse eventsMucosal melanomaAcute exudative polymorphous vitelliform maculopathyPotential immune-related adverse eventsBilateral visual field lossNew visual symptomsImmune checkpoint inhibitionRetrospective chart reviewCutaneous melanoma patientsVaried clinical manifestationsVisual field lossComplete ophthalmic examinationScreening of patientsMeta-Analyses (PRISMA) guidelinesPreferred Reporting ItemsVitelliform maculopathyChart reviewFunduscopic changes
2021
A Phase I Study of APX005M and Cabiralizumab with or without Nivolumab in Patients with Melanoma, Kidney Cancer, or Non–Small Cell Lung Cancer Resistant to Anti-PD-1/PD-L1
Weiss SA, Djureinovic D, Jessel S, Krykbaeva I, Zhang L, Jilaveanu L, Ralabate A, Johnson B, Levit NS, Anderson G, Zelterman D, Wei W, Mahajan A, Trifan O, Bosenberg M, Kaech SM, Perry CJ, Damsky W, Gettinger S, Sznol M, Hurwitz M, Kluger HM. A Phase I Study of APX005M and Cabiralizumab with or without Nivolumab in Patients with Melanoma, Kidney Cancer, or Non–Small Cell Lung Cancer Resistant to Anti-PD-1/PD-L1. Clinical Cancer Research 2021, 27: 4757-4767. PMID: 34140403, PMCID: PMC9236708, DOI: 10.1158/1078-0432.ccr-21-0903.Peer-Reviewed Original ResearchConceptsAnti-PD-1/PD-L1Non-small cell lung cancerCell lung cancerRenal cell carcinomaPD-L1Lung cancerDisease progressionCommon treatment-related adverse eventsPD-1/PD-L1 inhibitorsTreatment-related adverse eventsPhase 2 doseSubstantial clinical challengeUnconfirmed partial responseDose-limiting toxicityPD-L1 inhibitorsPhase I trialDose-escalation designPro-inflammatory cytokinesMultiple tumor typesAsymptomatic elevationStable diseaseIntolerable toxicityAdverse eventsMedian durationPartial response
2020
Bempegaldesleukin (NKTR-214) plus Nivolumab in Patients with Advanced Solid Tumors: Phase I Dose-Escalation Study of Safety, Efficacy, and Immune Activation (PIVOT-02)
Diab A, Tannir NM, Bentebibel SE, Hwu P, Papadimitrakopoulou V, Haymaker C, Kluger HM, Gettinger SN, Sznol M, Tykodi SS, Curti BD, Tagliaferri MA, Zalevsky J, Hannah AL, Hoch U, Aung S, Fanton C, Rizwan A, Iacucci E, Liao Y, Bernatchez C, Hurwitz ME, Cho DC. Bempegaldesleukin (NKTR-214) plus Nivolumab in Patients with Advanced Solid Tumors: Phase I Dose-Escalation Study of Safety, Efficacy, and Immune Activation (PIVOT-02). Cancer Discovery 2020, 10: 1158-1173. PMID: 32439653, DOI: 10.1158/2159-8290.cd-19-1510.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAntineoplastic Agents, ImmunologicalAntineoplastic Combined Chemotherapy ProtocolsCarcinoma, Non-Small-Cell LungCarcinoma, Renal CellFemaleGene Expression Regulation, NeoplasticHumansImmune Checkpoint InhibitorsImmunotherapyInterleukin-2Kidney NeoplasmsLung NeoplasmsLymphocyte CountLymphocytes, Tumor-InfiltratingMaleMelanomaMiddle AgedNivolumabPolyethylene GlycolsProgrammed Cell Death 1 ReceptorTreatment OutcomeYoung AdultConceptsTreatment-related adverse eventsAdvanced solid tumorsPD-L1 statusSolid tumorsGrade 3/4 treatment-related adverse eventsPD-1/PD-L1 blockadeCommon treatment-related adverse eventsPhase I dose-escalation trialPoor prognostic risk factorsTotal objective response rateI dose-escalation studyI dose-escalation trialLongitudinal tumor biopsiesPD-L1 blockadeT-cell enhancementTreatment-related deathsObjective response ratePhase II doseDose-escalation studyDose-escalation trialDose-limiting toxicityFlu-like symptomsPrognostic risk factorsTumor-infiltrating lymphocytesCytotoxicity of CD8
2019
Treatment-Free Survival: A Novel Outcome Measure of the Effects of Immune Checkpoint Inhibition—A Pooled Analysis of Patients With Advanced Melanoma
Regan MM, Werner L, Rao S, Gupte-Singh K, Hodi FS, Kirkwood JM, Kluger HM, Larkin J, Postow MA, Ritchings C, Sznol M, Tarhini AA, Wolchok JD, Atkins MB, McDermott DF. Treatment-Free Survival: A Novel Outcome Measure of the Effects of Immune Checkpoint Inhibition—A Pooled Analysis of Patients With Advanced Melanoma. Journal Of Clinical Oncology 2019, 37: 3350-3358. PMID: 31498030, PMCID: PMC6901280, DOI: 10.1200/jco.19.00345.Peer-Reviewed Original ResearchConceptsTreatment-related adverse eventsTreatment-free survivalHigher treatment-related adverse eventsKaplan-Meier curvesTherapy initiationAdvanced melanomaICI therapyEnd pointGrade 3Outcome measuresLonger treatment-free survivalImmuno-oncology agentsSystemic therapy initiationThird end pointTreatment-free timeImmune checkpoint inhibitionSurvival end pointsEvent end pointsNovel outcome measuresCheckMate 067ICI cessationAdverse eventsTherapy cessationCheckpoint inhibitionPooled analysisB cell depletion or absence does not impede anti-tumor activity of PD-1 inhibitors
Damsky W, Jilaveanu L, Turner N, Perry C, Zito C, Tomayko M, Leventhal J, Herold K, Meffre E, Bosenberg M, Kluger HM. B cell depletion or absence does not impede anti-tumor activity of PD-1 inhibitors. Journal For ImmunoTherapy Of Cancer 2019, 7: 153. PMID: 31200747, PMCID: PMC6567557, DOI: 10.1186/s40425-019-0613-1.Peer-Reviewed Original ResearchConceptsPD-1 inhibitorsB cell contentB-cell depletionAnti-tumor activityB cellsMuMT miceCell depletionAnti-PD-1 inhibitorsAnti-PD-1 responseB-cell depleting drugsTumor-infiltrating B cellsImpaired B-cell functionT cell-dependent tumor rejectionPD-1 inhibitionMC38 colon cancerB cell functionAnti-tumor effectsB-cell malignanciesMurine cancer modelsCell contentOverall survivalTumor rejectionCD20 antibodyAutoimmune disordersTumor shrinkageOphthalmic Immune-Related Adverse Events of Immunotherapy: A Single-Site Case Series
Kim J, Materin MA, Sznol M, Kluger H, Weiss S, Chow J, Stoessel K, Kombo N, Del Priore L, Pointdujour-Lim R. Ophthalmic Immune-Related Adverse Events of Immunotherapy: A Single-Site Case Series. Ophthalmology 2019, 126: 1058-1062. PMID: 30735682, PMCID: PMC6933747, DOI: 10.1016/j.ophtha.2019.01.031.Peer-Reviewed Original Research
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
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 cohortSarcoidosis Following Anti-PD-1 and Anti-CTLA-4 Therapy for Metastatic Melanoma
Reddy SB, Possick JD, Kluger HM, Galan A, Han D. Sarcoidosis Following Anti-PD-1 and Anti-CTLA-4 Therapy for Metastatic Melanoma. Journal Of Immunotherapy 2017, 40: 307-311. PMID: 28737620, DOI: 10.1097/cji.0000000000000181.Peer-Reviewed Case Reports and Technical NotesMeSH KeywordsAdrenal Cortex HormonesAntibodies, MonoclonalAntineoplastic Combined Chemotherapy ProtocolsAutoimmunityCTLA-4 AntigenDrug-Related Side Effects and Adverse ReactionsFemaleHumansImmunotherapyIpilimumabLungMelanomaMiddle AgedNivolumabProgrammed Cell Death 1 ReceptorSarcoidosisSkinSkin NeoplasmsTreatment OutcomeConceptsAnti-PD-1 therapyImmune checkpoint inhibitorsStage IV melanomaCheckpoint inhibitorsOncologic responseSevere immune-related adverse effectsImmune checkpoint inhibitor therapyImmune-related adverse effectsAnti PD-1Severe pulmonary manifestationsCheckpoint inhibitor therapyPD-1 inhibitorsDevelopment of sarcoidosisAutoimmune tendencyCorticosteroid treatmentLast dosePulmonary manifestationsCutaneous sarcoidosisRare complicationInhibitor therapyRadiologic findingsPatient's symptomsMetastatic melanomaPotential complicationsSarcoidosisPD-L1 Studies Across Tumor Types, Its Differential Expression and Predictive Value in Patients Treated with Immune Checkpoint Inhibitors
Kluger HM, Zito CR, Turcu G, Baine M, Zhang H, Adeniran A, Sznol M, Rimm DL, Kluger Y, Chen L, Cohen JV, Jilaveanu LB. PD-L1 Studies Across Tumor Types, Its Differential Expression and Predictive Value in Patients Treated with Immune Checkpoint Inhibitors. Clinical Cancer Research 2017, 23: 4270-4279. PMID: 28223273, PMCID: PMC5540774, DOI: 10.1158/1078-0432.ccr-16-3146.Peer-Reviewed Original ResearchConceptsNon-small cell lung cancerPD-L1 expressionRenal cell carcinomaPD-1 inhibitorsCell carcinomaImmune-infiltrating cellsMelanoma patientsPD-L1Tumor cellsTumor typesTumor-associated inflammatory cellsCTLA-4 inhibitorsCell lung cancerRenal cell carcinoma cellsHigh response rateClin Cancer ResCell linesMelanoma tumor cellsPD-1Multivariable analysisNSCLC specimensInflammatory cellsLung cancerTissue microarrayResponse rateNuclear 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
2016
Immunomodulatory Activity of Nivolumab in Metastatic Renal Cell Carcinoma
Choueiri TK, Fishman MN, Escudier B, McDermott DF, Drake CG, Kluger H, Stadler WM, Perez-Gracia JL, McNeel DG, Curti B, Harrison MR, Plimack ER, Appleman L, Fong L, Albiges L, Cohen L, Young TC, Chasalow SD, Ross-Macdonald P, Srivastava S, Jure-Kunkel M, Kurland JF, Simon JS, Sznol M. Immunomodulatory Activity of Nivolumab in Metastatic Renal Cell Carcinoma. Clinical Cancer Research 2016, 22: 5461-5471. PMID: 27169994, PMCID: PMC5106340, DOI: 10.1158/1078-0432.ccr-15-2839.Peer-Reviewed Original ResearchConceptsMetastatic renal cell carcinomaTreatment-naïve patientsPD-L1 expressionTumor-associated lymphocytesTreatment biopsiesOverall survivalAnti-PD-1 immune checkpoint inhibitorImmune checkpoint inhibitorsMedian overall survivalNew safety signalsPD-1 inhibitionPhase 3 trialMedian percent changeRenal cell carcinomaUpregulation of IFNγTumor gene expressionNivolumab dosesSerum chemokinesCheckpoint inhibitorsChemokine levelsBaseline biopsiesCell carcinomaImmunomodulatory effectsPeripheral bloodClinical activity
2015
Survival, Durable Response, and Long-Term Safety in Patients With Previously Treated Advanced Renal Cell Carcinoma Receiving Nivolumab
McDermott DF, Drake CG, Sznol M, Choueiri TK, Powderly JD, Smith DC, Brahmer JR, Carvajal RD, Hammers HJ, Puzanov I, Hodi FS, Kluger HM, Topalian SL, Pardoll DM, Wigginton JM, Kollia GD, Gupta A, McDonald D, Sankar V, Sosman JA, Atkins MB. Survival, Durable Response, and Long-Term Safety in Patients With Previously Treated Advanced Renal Cell Carcinoma Receiving Nivolumab. Journal Of Clinical Oncology 2015, 33: 2013-2020. PMID: 25800770, PMCID: PMC4517051, DOI: 10.1200/jco.2014.58.1041.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAntibodies, MonoclonalAntineoplastic AgentsCarcinoma, Renal CellCohort StudiesDisease-Free SurvivalDose-Response Relationship, DrugFemaleHumansKidney NeoplasmsMaleMaximum Tolerated DoseMiddle AgedNivolumabPatient SafetyProgrammed Cell Death 1 ReceptorTime FactorsTreatment OutcomeConceptsAdvanced renal cell carcinomaRenal cell carcinomaLong-term safetyOverall survivalDurable responsesTreatment-refractory solid tumorsTreatment-related adverse eventsOngoing randomized clinical trialsImpact of nivolumabMedian overall survivalMedian response durationPortion of patientsDuration of responseRandomized clinical trialsDrug discontinuationIntravenous nivolumabStable diseaseExpansion cohortTreatment discontinuationAdverse eventsObjective responseAdditional patientsAntibody nivolumabCell surface moleculesCell carcinomaPrecipitation of Autoimmune Diabetes With Anti-PD-1 Immunotherapy
Hughes J, Vudattu N, Sznol M, Gettinger S, Kluger H, Lupsa B, Herold KC. Precipitation of Autoimmune Diabetes With Anti-PD-1 Immunotherapy. Diabetes Care 2015, 38: e55-e57. PMID: 25805871, PMCID: PMC4370325, DOI: 10.2337/dc14-2349.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsCombination Therapy with Anti–CTLA-4 and Anti–PD-1 Leads to Distinct Immunologic Changes In Vivo
Das R, Verma R, Sznol M, Boddupalli CS, Gettinger SN, Kluger H, Callahan M, Wolchok JD, Halaban R, Dhodapkar MV, Dhodapkar KM. Combination Therapy with Anti–CTLA-4 and Anti–PD-1 Leads to Distinct Immunologic Changes In Vivo. The Journal Of Immunology 2015, 194: 950-959. PMID: 25539810, PMCID: PMC4380504, DOI: 10.4049/jimmunol.1401686.Peer-Reviewed Original ResearchMeSH KeywordsAntibodies, MonoclonalAntigens, SurfaceAntineoplastic Combined Chemotherapy ProtocolsCTLA-4 AntigenCytokinesGene Expression ProfilingGene Expression Regulation, NeoplasticHumansImmunophenotypingIpilimumabLymphocytes, Tumor-InfiltratingNeoplasmsNivolumabProgrammed Cell Death 1 ReceptorSignal TransductionT-Lymphocyte SubsetsConceptsPD-1T cellsCTLA-4Checkpoint blockadeCombination therapyReceptor occupancyCombination immune checkpoint blockadeCTLA-4 immune checkpointsPD-1 receptor occupancyTransitional memory T cellsAnti-PD-1 therapyAnti CTLA-4Immune-based combinationsPD-1 blockadeSoluble IL-2RImmune checkpoint blockadeNK cell functionMemory T cellsTherapy-induced changesT cell activationTumor T cellsHuman T cellsRemarkable antitumor effectImmunologic changesImmunologic effects
2014
Survival, Durable Tumor Remission, and Long-Term Safety in Patients With Advanced Melanoma Receiving Nivolumab
Topalian SL, Sznol M, McDermott DF, Kluger HM, Carvajal RD, Sharfman WH, Brahmer JR, Lawrence DP, Atkins MB, Powderly JD, Leming PD, Lipson EJ, Puzanov I, Smith DC, Taube JM, Wigginton JM, Kollia GD, Gupta A, Pardoll DM, Sosman JA, Hodi FS. Survival, Durable Tumor Remission, and Long-Term Safety in Patients With Advanced Melanoma Receiving Nivolumab. Journal Of Clinical Oncology 2014, 32: 1020-1030. PMID: 24590637, PMCID: PMC4811023, DOI: 10.1200/jco.2013.53.0105.Peer-Reviewed Original ResearchConceptsLong-term safetyOverall survivalToxicity ratesTumor regressionResponse durationOngoing randomized clinical trialsDurable tumor remissionNivolumab-treated patientsMedian overall survivalMedian response durationPD-1 blockadeObjective tumor regressionMaintenance of responseCell death 1Randomized clinical trialsSimilar patient populationsActivated T cellsDrug discontinuationIntravenous nivolumabNivolumab therapyNivolumab treatmentTreatment discontinuationObjective responseAdvanced melanomaDeath-1