2020
Revisiting anti-CTLA-4 antibodies in combination with PD-1 blockade for cancer immunotherapy
Sznol M, Melero I. Revisiting anti-CTLA-4 antibodies in combination with PD-1 blockade for cancer immunotherapy. Annals Of Oncology 2020, 32: 295-297. PMID: 33307201, DOI: 10.1016/j.annonc.2020.11.018.Peer-Reviewed Original Research
2019
Immunotherapy of Melanoma: Facts and Hopes
Weiss SA, Wolchok JD, Sznol M. Immunotherapy of Melanoma: Facts and Hopes. Clinical Cancer Research 2019, 25: 5191-5201. PMID: 30923036, PMCID: PMC6726509, DOI: 10.1158/1078-0432.ccr-18-1550.Peer-Reviewed Original ResearchConceptsOverall survivalMetastatic diseaseImmune therapyPredictive biomarkersNivolumab/ipilimumab combinationRandomized phase III trialLong-term clinical benefitImmunobiology of tumorsDuration of therapyPhase III trialsLong-term survivorsEffective immune therapyAdjuvant settingIpilimumab combinationMetastatic settingIII trialsPatient subsetsClinical benefitImmune modulationMetastatic melanomaClinical trialsSingle agentTherapyTrue increaseCell therapyPatterns of failure after immunotherapy with checkpoint inhibitors predict durable progression-free survival after local therapy for metastatic melanoma
Klemen ND, Wang M, Feingold PL, Cooper K, Pavri SN, Han D, Detterbeck FC, Boffa DJ, Khan SA, Olino K, Clune J, Ariyan S, Salem RR, Weiss SA, Kluger HM, Sznol M, Cha C. Patterns of failure after immunotherapy with checkpoint inhibitors predict durable progression-free survival after local therapy for metastatic melanoma. Journal For ImmunoTherapy Of Cancer 2019, 7: 196. PMID: 31340861, PMCID: PMC6657062, DOI: 10.1186/s40425-019-0672-3.Peer-Reviewed Original ResearchConceptsThree-year progression-free survivalProgression-free survivalDisease-specific survivalFive-year disease-specific survivalPatterns of failureDurable progression-free survivalLocal therapyStereotactic body radiotherapyMetastatic melanomaNew metastasesPatient selectionIndependent radiological reviewOngoing complete responseResultsFour hundred twentyEvidence of diseaseCNS metastasisCPI treatmentImmunotherapy failureCheckpoint inhibitorsMost patientsProgressive diseaseRadiological reviewComplete responsePD-1PD-L1
2018
A Serum Protein Signature Associated with Outcome after Anti–PD-1 Therapy in Metastatic Melanoma
Weber JS, Sznol M, Sullivan RJ, Blackmon S, Boland G, Kluger HM, Halaban R, Bacchiocchi A, Ascierto PA, Capone M, Oliveira C, Meyer K, Grigorieva J, Asmellash SG, Roder J, Roder H. A Serum Protein Signature Associated with Outcome after Anti–PD-1 Therapy in Metastatic Melanoma. Cancer Immunology Research 2018, 6: 79-86. PMID: 29208646, DOI: 10.1158/2326-6066.cir-17-0412.Peer-Reviewed Original ResearchConceptsAcute phase reactantsCheckpoint inhibitorsOverall survivalPhase reactantsIpilimumab-treated patientsPD-1 blockadeTrials of nivolumabBetter overall survivalIndependent patient cohortsPretreatment serumPD-1Melanoma patientsValidation cohortMetastatic melanomaMultipeptide vaccinePatient cohortPooled analysisWorse outcomesClinical dataPatientsMultivariate analysisComplement cascadeMass spectrometry analysisNivolumabCohort
2017
Endocrine-related adverse events associated with immune checkpoint blockade and expert insights on their management
Sznol M, Postow MA, Davies MJ, Pavlick AC, Plimack ER, Shaheen M, Veloski C, Robert C. Endocrine-related adverse events associated with immune checkpoint blockade and expert insights on their management. Cancer Treatment Reviews 2017, 58: 70-76. PMID: 28689073, DOI: 10.1016/j.ctrv.2017.06.002.Peer-Reviewed Original ResearchConceptsImmune-related adverse eventsImmune checkpoint inhibitorsCytotoxic T-lymphocyte antigen-4Checkpoint inhibitorsEndocrine eventsAdverse eventsTypes of irAEsEndocrine-related adverse eventsT-lymphocyte antigen-4Replacement of hormonesDeath receptor-1Target organ damageClose patient monitoringImmune checkpoint blockadeNon-specific symptomsAppropriate laboratory testingImmune checkpoint proteinsCheckpoint blockadeGrade 1/2Organ damageClinical benefitAdrenal glandAntigen-4Endocrine functionGastrointestinal tract
2015
Nivolumab versus chemotherapy in patients with advanced melanoma who progressed after anti-CTLA-4 treatment (CheckMate 037): a randomised, controlled, open-label, phase 3 trial
Weber JS, D'Angelo SP, Minor D, Hodi FS, Gutzmer R, Neyns B, Hoeller C, Khushalani NI, Miller WH, Lao CD, Linette GP, Thomas L, Lorigan P, Grossmann KF, Hassel JC, Maio M, Sznol M, Ascierto PA, Mohr P, Chmielowski B, Bryce A, Svane IM, Grob JJ, Krackhardt AM, Horak C, Lambert A, Yang AS, Larkin J. Nivolumab versus chemotherapy in patients with advanced melanoma who progressed after anti-CTLA-4 treatment (CheckMate 037): a randomised, controlled, open-label, phase 3 trial. The Lancet Oncology 2015, 16: 375-384. PMID: 25795410, DOI: 10.1016/s1470-2045(15)70076-8.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAntibodies, MonoclonalAntineoplastic Combined Chemotherapy ProtocolsCarboplatinCTLA-4 AntigenDisease-Free SurvivalDrug-Related Side Effects and Adverse ReactionsFemaleHumansIpilimumabMaleMelanomaMiddle AgedNeoplasm StagingNivolumabPaclitaxelProto-Oncogene Proteins B-rafConceptsPhase 3 trialObjective responseAdvanced melanomaBRAF inhibitorsPrimary endpointAdverse eventsGrade 3Human IgG4 PD-1 immune checkpoint inhibitor antibodyDrug-related serious adverse eventsICC groupImmune checkpoint inhibitor antibodyCheckpoint inhibitor antibodyDurable objective responsesLater-line treatmentNivolumab-treated patientsSafety of nivolumabTreatment-related deathsUnacceptable toxic effectsSerious adverse eventsProportion of patientsFirst interim analysisNew treatment optionsBest overall responseDose of treatmentHigh unmet needTherapeutic Combinations of Immune-Modulating Antibodies in Melanoma and Beyond
Cohen J, Sznol M. Therapeutic Combinations of Immune-Modulating Antibodies in Melanoma and Beyond. Seminars In Oncology 2015, 42: 488-494. PMID: 25965368, DOI: 10.1053/j.seminoncol.2015.02.014.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntibodies, MonoclonalAntineoplastic Combined Chemotherapy ProtocolsCTLA-4 AntigenHumansImmunologic FactorsMelanomaConceptsImmune modulating antibodiesCheckpoint inhibitorsMetastatic renal cell carcinomaPD-1/PD-L1 antagonistsSelection of patientsPD-L1 antagonistsRenal cell carcinomaNumber of malignanciesAutoimmune toxicityCell carcinomaCombination therapyMetastatic melanomaTherapeutic combinationsSingle agentCostimulatory agentsOptimal outcomesAntibodiesPatientsMalignancyPromising activityMelanomaFuture combinationInhibitorsCarcinomaAgonistsCombination 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
2013
Nivolumab plus Ipilimumab in Advanced Melanoma
Wolchok JD, Kluger H, Callahan MK, Postow MA, Rizvi NA, Lesokhin AM, Segal NH, Ariyan CE, Gordon RA, Reed K, Burke MM, Caldwell A, Kronenberg SA, Agunwamba BU, Zhang X, Lowy I, Inzunza HD, Feely W, Horak CE, Hong Q, Korman AJ, Wigginton JM, Gupta A, Sznol M. Nivolumab plus Ipilimumab in Advanced Melanoma. New England Journal Of Medicine 2013, 369: 122-133. PMID: 23724867, PMCID: PMC5698004, DOI: 10.1056/nejmoa1302369.Peer-Reviewed Original ResearchConceptsObjective response ratePhase 1 trialAdverse eventsConcurrent therapyAdvanced melanomaTumor regressionClinical activityGrade 3Distinct immunologic mechanismsManageable safety profileProlongs overall survivalDurable tumor regressionSupportive preclinical dataRegimen groupImmunologic mechanismsObjective responseOverall survivalIntravenous dosesSafety profileTumor reductionPreclinical dataIpilimumabNivolumabPatientsMaximum doses
2012
Advances in the Treatment of Metastatic Melanoma: New Immunomodulatory Agents
Sznol M. Advances in the Treatment of Metastatic Melanoma: New Immunomodulatory Agents. Seminars In Oncology 2012, 39: 192-203. PMID: 22484191, DOI: 10.1053/j.seminoncol.2012.01.007.Peer-Reviewed Original ResearchConceptsNew immunomodulatory agentsImmunomodulatory agentsMetastatic melanomaT cell activationT cellsAdverse eventsDendritic cellsClinical activityOngoing phase III trialsRandomized phase III studyCo-inhibitory receptor PD-1Co-stimulatory antibodiesMajor adverse eventsPhase III studyPhase III trialsReceptor PD-1Durable clinical responsesImmune cell subsetsSubsequent clinical trialsParticular T cellsActivated T cellsMechanism of actionAdvanced diseaseClinical responseIII study
2011
Integrated NY-ESO-1 antibody and CD8+ T-cell responses correlate with clinical benefit in advanced melanoma patients treated with ipilimumab
Yuan J, Adamow M, Ginsberg BA, Rasalan TS, Ritter E, Gallardo HF, Xu Y, Pogoriler E, Terzulli SL, Kuk D, Panageas KS, Ritter G, Sznol M, Halaban R, Jungbluth AA, Allison JP, Old LJ, Wolchok JD, Gnjatic S. Integrated NY-ESO-1 antibody and CD8+ T-cell responses correlate with clinical benefit in advanced melanoma patients treated with ipilimumab. Proceedings Of The National Academy Of Sciences Of The United States Of America 2011, 108: 16723-16728. PMID: 21933959, PMCID: PMC3189057, DOI: 10.1073/pnas.1110814108.Peer-Reviewed Original ResearchConceptsNY-ESO-1-seropositive patientsNY-ESO-1 antibodyT cell responsesClinical benefitImmune responseIpilimumab treatmentNY-ESO-1 immune responsesNY-ESO-1 serum antibodyTumor antigen-specific immune responsesCytotoxic T-lymphocyte antigen-4NY-ESO-1 immunityT-lymphocyte antigen-4Antigen-specific immune responsesIpilimumab-treated patientsAdvanced melanoma patientsAdvanced metastatic melanomaCancer/testis antigensSubset of patientsNY-ESO-1Significant survival advantageCD8 responsesAdoptive transferClinical outcomesMelanoma patientsProspective study
2009
Betting on immunotherapy for melanoma
Sznol M. Betting on immunotherapy for melanoma. Current Oncology Reports 2009, 11: 397-404. PMID: 19679015, DOI: 10.1007/s11912-009-0053-z.Peer-Reviewed Original ResearchMeSH KeywordsAntibodies, MonoclonalAntigens, CDCTLA-4 AntigenHumansImmunotherapyIpilimumabMelanomaTreatment OutcomeConceptsAdvanced melanomaAntigen-specific T cell expansionEffective antitumor immune responseAntitumor immune responseEffective treatment optionT cell expansionAntigen-specific lymphocytesTumor defense mechanismsDurable remissionsPreparative regimensConditioning regimensAdoptive immunotherapyImmune therapyCancer vaccinesImmune activationTreatment optionsPredictive biomarkersPrimary tumorTumor immunobiologyClinical trialsAntigen presentationImmune responseHigh riskNew cytokinePatients
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 ResearchConceptsIL-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