2021
Outcomes of Stereotactic Radiosurgery and Immunotherapy in Renal Cell Carcinoma Patients With Brain Metastases
Uezono H, Nam D, Kluger HM, Sznol M, Hurwitz M, Yu JB, Chiang VL. Outcomes of Stereotactic Radiosurgery and Immunotherapy in Renal Cell Carcinoma Patients With Brain Metastases. American Journal Of Clinical Oncology 2021, 44: 495-501. PMID: 34432667, DOI: 10.1097/coc.0000000000000849.Peer-Reviewed Original ResearchConceptsImmune checkpoint inhibitorsRCC brain metastasesBrain metastasesRenal cell carcinomaStereotactic radiosurgeryOverall survivalUse of ICIsCentral nervous system toxicityRenal cell carcinoma patientsImpact of immunotherapyLocal control outcomesMedian overall survivalCell carcinoma patientsKaplan-Meier curvesNervous system toxicityBetter median OSLog-rank testMann-Whitney U testMargin doseMedian OSNonimmunotherapy groupSRS doseCheckpoint inhibitorsImmunotherapy groupCarcinoma patientsMolecular correlates of response to nivolumab at baseline and on treatment in patients with RCC
Ross-Macdonald P, Walsh AM, Chasalow SD, Ammar R, Papillon-Cavanagh S, Szabo PM, Choueiri TK, Sznol M, Wind-Rotolo M. Molecular correlates of response to nivolumab at baseline and on treatment in patients with RCC. Journal For ImmunoTherapy Of Cancer 2021, 9: e001506. PMID: 33658305, PMCID: PMC7931766, DOI: 10.1136/jitc-2020-001506.Peer-Reviewed Original ResearchMeSH KeywordsB7-H1 AntigenBiomarkers, TumorCarcinoma, Renal CellCD4 AntigensCD8 AntigensCytokinesDrug Resistance, NeoplasmHumansImmune Checkpoint InhibitorsKidney NeoplasmsLymphocytes, Tumor-InfiltratingMutationNivolumabProgrammed Cell Death 1 ReceptorReceptors, Antigen, T-CellTime FactorsT-LymphocytesTreatment OutcomeConceptsClear cell renal cell carcinomaMetastatic clear cell renal cell carcinomaT cell infiltrationNivolumab responseExact testDeath ligand 1 (PD-L1) statusFirst-line treatment decisionsT-cell receptor clonalitySerum cytokine assaysImmune checkpoint inhibitorsNon-responding patientsDeath-1 receptorCell renal cell carcinomaSubset of patientsRenal cell carcinomaFisher's exact testWnt/β-cateninLogistic regression modelsRank sum testCD8 statusCheckpoint inhibitorsIndex lesionPatient selectionTCR clonalityCell carcinoma
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
A First-in-Human Study and Biomarker Analysis of NKTR-214, a Novel IL2Rβγ-Biased Cytokine, in Patients with Advanced or Metastatic Solid Tumors
Bentebibel SE, Hurwitz ME, Bernatchez C, Haymaker C, Hudgens CW, Kluger HM, Tetzlaff MT, Tagliaferri MA, Zalevsky J, Hoch U, Fanton C, Aung S, Hwu P, Curti BD, Tannir NM, Sznol M, Diab A. A First-in-Human Study and Biomarker Analysis of NKTR-214, a Novel IL2Rβγ-Biased Cytokine, in Patients with Advanced or Metastatic Solid Tumors. Cancer Discovery 2019, 9: 711-721. PMID: 30988166, DOI: 10.1158/2159-8290.cd-18-1495.Peer-Reviewed Original ResearchConceptsNKTR-214Tumor biopsiesDurable disease stabilizationImmuno-oncology agentsMulticenter phase IPathway-targeted agentsTreatment tumor biopsiesPhase II doseActivation of CD8Metastatic solid tumorsNatural killer cellsOutpatient regimenCheckpoint inhibitorsDisease stabilizationRegulatory cellsEffector phenotypeKiller cellsTreatment algorithmImmune activationTumor shrinkagePharmacodynamic markersImmune cellsClinical activityIL2 receptorHuman studies
2018
Bullous disorders associated with anti–PD-1 and anti–PD-L1 therapy: A retrospective analysis evaluating the clinical and histopathologic features, frequency, and impact on cancer therapy
Siegel J, Totonchy M, Damsky W, Berk-Krauss J, Castiglione F, Sznol M, Petrylak DP, Fischbach N, Goldberg SB, Decker RH, Stamatouli AM, Hafez N, Glusac EJ, Tomayko MM, Leventhal JS. Bullous disorders associated with anti–PD-1 and anti–PD-L1 therapy: A retrospective analysis evaluating the clinical and histopathologic features, frequency, and impact on cancer therapy. Journal Of The American Academy Of Dermatology 2018, 79: 1081-1088. PMID: 30025829, DOI: 10.1016/j.jaad.2018.07.008.Peer-Reviewed Original ResearchMeSH KeywordsAdrenal Cortex HormonesAgedAntibodies, MonoclonalAntibodies, Monoclonal, HumanizedAntineoplastic Agents, ImmunologicalB7-H1 AntigenDrug EruptionsFemaleHumansLichenoid EruptionsMaleMiddle AgedNeoplasm ProteinsNeoplasmsNivolumabPemphigoid, BullousProgrammed Cell Death 1 ReceptorRetrospective StudiesSkin Diseases, VesiculobullousTertiary Care CentersTreatment OutcomeConceptsPD-L1 therapyAnti-PD-1/PD-L1 therapyBullous disordersBullous eruptionPD-1/PD-L1 therapyCell death ligand-1 therapyAnti-programmed cell death 1Cancer therapyDeath ligand 1 therapySingle tertiary care centerLinear IgA bullous dermatosisYale-New Haven HospitalDistinct therapeutic challengesInterruption of immunotherapyPositive tumor responseSteroid-sparing agentTertiary care centerIgA bullous dermatosisCell death 1New Haven HospitalStable diseaseSystemic corticosteroidsSystemic steroidsMaintenance therapyL1 therapyClinical activity and molecular correlates of response to atezolizumab alone or in combination with bevacizumab versus sunitinib in renal cell carcinoma
McDermott DF, Huseni MA, Atkins MB, Motzer RJ, Rini BI, Escudier B, Fong L, Joseph RW, Pal SK, Reeves JA, Sznol M, Hainsworth J, Rathmell WK, Stadler WM, Hutson T, Gore ME, Ravaud A, Bracarda S, Suárez C, Danielli R, Gruenwald V, Choueiri TK, Nickles D, Jhunjhunwala S, Piault-Louis E, Thobhani A, Qiu J, Chen DS, Hegde PS, Schiff C, Fine GD, Powles T. Clinical activity and molecular correlates of response to atezolizumab alone or in combination with bevacizumab versus sunitinib in renal cell carcinoma. Nature Medicine 2018, 24: 749-757. PMID: 29867230, PMCID: PMC6721896, DOI: 10.1038/s41591-018-0053-3.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAntibodies, MonoclonalAntibodies, Monoclonal, HumanizedAntineoplastic Combined Chemotherapy ProtocolsBevacizumabCarcinoma, Renal CellFemaleGene Expression ProfilingGene Expression Regulation, NeoplasticHumansKaplan-Meier EstimateKidney NeoplasmsMaleMiddle AgedMutationSunitinibTreatment OutcomeConceptsProgression-free survivalPFS hazard ratioRenal cell carcinomaHazard ratioPD-L1Cell carcinomaTreatment-naive metastatic renal-cell carcinomaRandomized phase 2 studyMetastatic renal cell carcinomaInflammatory gene expression signatureExploratory biomarker analysisPhase 2 studyImmune checkpoint blockadeCo-primary endpointsPrediction of outcomeAtezolizumab monotherapyCheckpoint blockadeGene expression signaturesNeoantigen burdenT effectorsClinical activityAtezolizumabBevacizumabTumor mutationsSunitinibFirst-in-Class ERK1/2 Inhibitor Ulixertinib (BVD-523) in Patients with MAPK Mutant Advanced Solid Tumors: Results of a Phase I Dose-Escalation and Expansion Study
Sullivan RJ, Infante JR, Janku F, Wong DJL, Sosman JA, Keedy V, Patel MR, Shapiro GI, Mier JW, Tolcher AW, Wang-Gillam A, Sznol M, Flaherty K, Buchbinder E, Carvajal RD, Varghese AM, Lacouture ME, Ribas A, Patel SP, DeCrescenzo GA, Emery CM, Groover AL, Saha S, Varterasian M, Welsch DJ, Hyman DM, Li BT. First-in-Class ERK1/2 Inhibitor Ulixertinib (BVD-523) in Patients with MAPK Mutant Advanced Solid Tumors: Results of a Phase I Dose-Escalation and Expansion Study. Cancer Discovery 2018, 8: 184-195. PMID: 29247021, DOI: 10.1158/2159-8290.cd-17-1119.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAminopyridinesFemaleHumansMagnetic Resonance ImagingMaleMiddle AgedMitogen-Activated Protein Kinase 1Mitogen-Activated Protein Kinase 3Mitogen-Activated Protein KinasesMutationNeoplasm StagingNeoplasmsProtein Kinase InhibitorsPyrrolesTomography, X-Ray ComputedTreatment OutcomeYoung AdultConceptsCommon treatment-related adverse eventsSolid tumorsHuman dose-escalation studyMulticenter phase I trialTreatment-related adverse eventsDose-escalation cohortsDose-expansion cohortsMutant solid tumorsPhase II doseAcceptable safety profileAdvanced solid tumorsDose-escalation studyPhase I trialPotent preclinical activityTreatment of patientsSolid tumor malignanciesERK1/2 kinase inhibitorEvaluable patientsDose expansionExpansion cohortAdverse eventsPartial responseDose escalationI trialSafety profileA 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
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 cohortPhase Ib Study of Utomilumab (PF-05082566), a 4-1BB/CD137 Agonist, in Combination with Pembrolizumab (MK-3475) in Patients with Advanced Solid Tumors
Tolcher AW, Sznol M, Hu-Lieskovan S, Papadopoulos KP, Patnaik A, Rasco DW, Di Gravio D, Huang B, Gambhire D, Chen Y, Thall AD, Pathan N, Schmidt EV, Chow LQM. Phase Ib Study of Utomilumab (PF-05082566), a 4-1BB/CD137 Agonist, in Combination with Pembrolizumab (MK-3475) in Patients with Advanced Solid Tumors. Clinical Cancer Research 2017, 23: 5349-5357. PMID: 28634283, DOI: 10.1158/1078-0432.ccr-17-1243.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAntibodies, MonoclonalAntibodies, Monoclonal, HumanizedAntineoplastic Combined Chemotherapy ProtocolsCombined Modality TherapyDiagnostic ImagingDrug MonitoringFemaleHumansImmunoglobulin GMaleMaximum Tolerated DoseMiddle AgedMolecular Targeted TherapyNeoplasm StagingNeoplasmsRetreatmentT-Lymphocyte SubsetsTreatment OutcomeTumor Necrosis Factor Receptor Superfamily, Member 9ConceptsAdvanced solid tumorsSolid tumorsTreatment-emergent adverse eventsPeripheral blood CD8Phase Ib studyTreatment-related discontinuationsDose-limiting toxicityCostimulatory receptor 4Event continual reassessment methodT cell costimulatory receptor 4Clin Cancer ResSupport further investigationBlood CD8Partial responseAdverse eventsDose escalationReceptor 4Clinical activityT cellsIb studyCombination treatmentContinual reassessment methodPatientsGrade 1Cancer Res
2016
Atezolizumab in combination with bevacizumab enhances antigen-specific T-cell migration in metastatic renal cell carcinoma
Wallin JJ, Bendell JC, Funke R, Sznol M, Korski K, Jones S, Hernandez G, Mier J, He X, Hodi FS, Denker M, Leveque V, Cañamero M, Babitski G, Koeppen H, Ziai J, Sharma N, Gaire F, Chen DS, Waterkamp D, Hegde PS, McDermott DF. Atezolizumab in combination with bevacizumab enhances antigen-specific T-cell migration in metastatic renal cell carcinoma. Nature Communications 2016, 7: 12624. PMID: 27571927, PMCID: PMC5013615, DOI: 10.1038/ncomms12624.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAntibodies, MonoclonalAntibodies, Monoclonal, HumanizedAntigens, NeoplasmAntineoplastic Combined Chemotherapy ProtocolsB7-H1 AntigenBevacizumabCarcinoma, Renal CellCD8-Positive T-LymphocytesCell MovementDrug SynergismFemaleHumansKidneyKidney NeoplasmsMaleMaximum Tolerated DoseMiddle AgedTreatment OutcomeVascular Endothelial Growth Factor AConceptsAntigen-specific T-cell migrationT cell migrationT cellsCombination treatmentAnti-tumor immune activationPD-L1 checkpoint inhibitionMetastatic renal cell carcinomaAddition of atezolizumabIntra-tumoral CD8Subset of patientsT cell infiltrationImmune cell activityRenal cell carcinomaEndothelial cell activationVariety of cancersLymphocytes increasesPeripheral CD8Checkpoint inhibitorsDurable responsesCheckpoint inhibitionImmune activationCell carcinomaVascular normalizationReceptor increasesCell activationCyclosporine for Dry Eye Associated With Nivolumab
Nguyen AT, Elia M, Materin MA, Sznol M, Chow J. Cyclosporine for Dry Eye Associated With Nivolumab. Cornea 2016, 35: 399-401. PMID: 26771550, DOI: 10.1097/ico.0000000000000724.Peer-Reviewed Original ResearchConceptsDry eye diseaseMetastatic melanomaTopical cyclosporineCorneal perforationDry eyeEye diseaseSevere dry eye symptomsBilateral dry eyesDry Eye AssociatedOcular surface inflammationSevere dry eyeDry eye symptomsImprovement of symptomsNivolumab therapyIntensive regimenSurface inflammationEye symptomsMetastatic diseaseClinical outcomesAggressive lubricationRight eyeCase reportNivolumabOcular surfaceAntitumor effects
2015
Overall Survival and Long-Term Safety of Nivolumab (Anti–Programmed Death 1 Antibody, BMS-936558, ONO-4538) in Patients With Previously Treated Advanced Non–Small-Cell Lung Cancer
Gettinger SN, Horn L, Gandhi L, Spigel DR, Antonia SJ, Rizvi NA, Powderly JD, Heist RS, Carvajal RD, Jackman DM, Sequist LV, Smith DC, Leming P, Carbone DP, Pinder-Schenck MC, Topalian SL, Hodi FS, Sosman JA, Sznol M, McDermott DF, Pardoll DM, Sankar V, Ahlers CM, Salvati M, Wigginton JM, Hellmann MD, Kollia GD, Gupta AK, Brahmer JR. Overall Survival and Long-Term Safety of Nivolumab (Anti–Programmed Death 1 Antibody, BMS-936558, ONO-4538) in Patients With Previously Treated Advanced Non–Small-Cell Lung Cancer. Journal Of Clinical Oncology 2015, 33: 2004-2012. PMID: 25897158, PMCID: PMC4672027, DOI: 10.1200/jco.2014.58.3708.Peer-Reviewed Original ResearchConceptsOverall survivalLong-term safetyAdvanced NSCLCLung cancerDeath-1 immune checkpoint inhibitor antibodyAdvanced non-small cell lung cancerNon-small cell lung cancerImmune checkpoint inhibitor antibodyTreatment-related adverse eventsCheckpoint inhibitor antibodyTreatment-related deathsMedian overall survivalMedian response durationAdvanced solid tumorsPhase I trialCell lung cancerRandomized clinical trialsFurther clinical developmentHuman immunoglobulin G4Nivolumab 1Nivolumab monotherapyExpansion cohortLast doseNonsquamous NSCLCAdverse eventsSurvival, 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 carcinoma
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
2012
Ipilimumab in patients with melanoma and brain metastases: an open-label, phase 2 trial
Margolin K, Ernstoff MS, Hamid O, Lawrence D, McDermott D, Puzanov I, Wolchok JD, Clark JI, Sznol M, Logan TF, Richards J, Michener T, Balogh A, Heller KN, Hodi FS. Ipilimumab in patients with melanoma and brain metastases: an open-label, phase 2 trial. The Lancet Oncology 2012, 13: 459-465. PMID: 22456429, DOI: 10.1016/s1470-2045(12)70090-6.Peer-Reviewed Original ResearchConceptsBrain metastasesCohort ACohort BSerum aspartate aminotransferaseDisease controlIntravenous ipilimumabAdverse eventsAdvanced melanomaCohort B.Common grade 3 adverse eventsAspartate aminotransferaseGrade 3 adverse eventsCommon grade 3Drug-related complicationsPhase 2 trialProportion of patientsUnexpected toxic effectsBristol-Myers SquibbStable diseaseCorticosteroid treatmentPrimary endpointStable dosePartial responseWeek 24Complete response
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
2007
A Phase I study of the novel ribonucleotide reductase inhibitor 3-aminopyridine-2-carboxaldehyde thiosemicarbazone (3-AP, Triapine®) in combination with the nucleoside analog fludarabine for patients with refractory acute leukemias and aggressive myeloproliferative disorders
Karp JE, Giles FJ, Gojo I, Morris L, Greer J, Johnson B, Thein M, Sznol M, Low J. A Phase I study of the novel ribonucleotide reductase inhibitor 3-aminopyridine-2-carboxaldehyde thiosemicarbazone (3-AP, Triapine®) in combination with the nucleoside analog fludarabine for patients with refractory acute leukemias and aggressive myeloproliferative disorders. Leukemia Research 2007, 32: 71-77. PMID: 17640728, PMCID: PMC2726775, DOI: 10.1016/j.leukres.2007.05.003.Peer-Reviewed Original ResearchConceptsAggressive myeloproliferative disorderDaily x 5Refractory acute leukemiaMyeloproliferative disordersAcute leukemiaRibonucleotide reductase inhibitorReductase inhibitorsDays of fludarabineRefractory myeloid malignanciesPhase I trialDrug-related toxicityNovel ribonucleotide reductase inhibitorNucleoside analog fludarabinePotent ribonucleotide reductase inhibitorPartial responseI trialMetabolic acidosisSchedule AFludarabineMyeloid malignanciesPatientsPhase ILeukemiaDisordersInhibitors
2006
Triapine and cytarabine is an active combination in patients with acute leukemia or myelodysplastic syndrome
Yee KW, Cortes J, Ferrajoli A, Garcia-Manero G, Verstovsek S, Wierda W, Thomas D, Faderl S, King I, O’Brien S, Jeha S, Andreeff M, Cahill A, Sznol M, Giles FJ. Triapine and cytarabine is an active combination in patients with acute leukemia or myelodysplastic syndrome. Leukemia Research 2006, 30: 813-822. PMID: 16478631, DOI: 10.1016/j.leukres.2005.12.013.Peer-Reviewed Original ResearchMeSH KeywordsAcute DiseaseAdolescentAdultAgedAged, 80 and overAntineoplastic Combined Chemotherapy ProtocolsCytarabineDose-Response Relationship, DrugDrug Administration ScheduleDrug CombinationsFemaleHumansInjections, IntravenousLeukemia, MyeloidMaleMaximum Tolerated DoseMiddle AgedMyelodysplastic SyndromesPyridinesRecurrenceRisk FactorsThiosemicarbazonesTreatment OutcomeConceptsAra-C dose levelsDose levelsM2/dayAcute leukemiaSignificant anti-leukemia activityConsecutive daysPhase II regimenRefractory acute leukemiaHigh-risk MDSAnti-leukemia activityEvaluable patientsMyelodysplastic syndromeActive combinationPatientsPhase IIron chelatorsLeukemiaAraPotent inhibitorDaysTriapineRegimenCytarabineInfusionSyndrome
2005
Phase I Study of the Sequential Combination of Interleukin-12 and Interferon Alfa-2b in Advanced Cancer: Evidence for Modulation of Interferon Signaling Pathways by Interleukin-12
Eisenbeis CF, Lesinski GB, Anghelina M, Parihar R, Valentino D, Liu J, Nadella P, Sundaram P, Young DC, Sznol M, Walker MJ, Carson WE. Phase I Study of the Sequential Combination of Interleukin-12 and Interferon Alfa-2b in Advanced Cancer: Evidence for Modulation of Interferon Signaling Pathways by Interleukin-12. Journal Of Clinical Oncology 2005, 23: 8835-8844. PMID: 16314644, DOI: 10.1200/jco.2005.02.1691.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAntineoplastic AgentsAntineoplastic Combined Chemotherapy ProtocolsDose-Response Relationship, DrugHumansInterferon alpha-2Interferon-alphaInterferon-gammaInterleukin-12Leukocytes, MononuclearMiddle AgedNeoplasmsRecombinant ProteinsSignal TransductionSTAT1 Transcription FactorTime FactorsTreatment OutcomeConceptsPatients' peripheral blood mononuclear cellsPatient PBMCsInterferon alfa-2bIFN-gammaInterleukin-12Alfa-2bRhIL-12Advanced cancerIL-12Greater IFN-gamma productionPeripheral blood mononuclear cellsPeak levelsIL-12 administrationPlasma IFN-gammaIL-12 therapyDose-limiting toxicityIFN-gamma productionHuman interleukin-12Interferon Signaling PathwayAssessable patientsIntracellular STAT1Stable diseasePeripheral bloodMononuclear cellsLevels of STAT1