2024
Patterns of brain metastases response to immunotherapy with pembrolizumab
Mahajan A, Goldberg S, Weiss S, Tran T, Singh K, Joshi K, Aboian M, Kluger H, Chiang V. Patterns of brain metastases response to immunotherapy with pembrolizumab. Journal Of Neuro-Oncology 2024, 1-7. PMID: 38963658, DOI: 10.1007/s11060-024-04754-8.Peer-Reviewed Original ResearchNon-small cell lung cancerBrain metastasesComplete resolutionLung cancerMedian time to CNS progressionLesion progressionNon-small cell lung cancer patientsModified RECIST criteriaPD-1 inhibitorsTrial of pembrolizumabEffective systemic treatmentResponse to immunotherapyPhase II trialCell lung cancerMethodsThis retrospective studyLocal treatment decisionsPurposeCentral nervous systemCNS progressionRECIST criteriaPD-1Local therapySystemic treatmentMRI evaluationResponse assessmentRetrospective study
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 ResearchConceptsStable 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 analysisUse of immune checkpoint inhibitors in solid organ transplant recipients with advanced cutaneous malignancies
Ji S, Liu H, Pachella L, Stephenson R, Groisberg R, Weiss S. Use of immune checkpoint inhibitors in solid organ transplant recipients with advanced cutaneous malignancies. Frontiers In Transplantation 2023, 2: 1284740. PMID: 38993910, PMCID: PMC11235332, DOI: 10.3389/frtra.2023.1284740.Peer-Reviewed Original ResearchImmune checkpoint inhibitorsCutaneous squamous cell carcinomaObjective response rateMerkel cell carcinomaSolid organ transplant recipientsOrgan transplant recipientsSOT recipientsGraft rejectionCutaneous malignanciesCheckpoint inhibitorsTransplant recipientsCell carcinomaRetrospective analysisFirst-line immune checkpoint inhibitorsPrior systemic therapyAdvanced skin cancerSquamous cell carcinomaAdvanced cutaneous malignanciesImmunosuppressive therapyAllograft rejectionGraft failureSystemic therapyAdvanced melanomaCare therapyImmunosuppressive agentsSociety for Immunotherapy of Cancer (SITC) clinical practice guideline on immunotherapy for the treatment of melanoma, version 3.0
Pavlick A, Ariyan C, Buchbinder E, Davar D, Gibney G, Hamid O, Hieken T, Izar B, Johnson D, Kulkarni R, Luke J, Mitchell T, Mooradian M, Rubin K, Salama A, Shirai K, Taube J, Tawbi H, Tolley J, Valdueza C, Weiss S, Wong M, Sullivan R. Society for Immunotherapy of Cancer (SITC) clinical practice guideline on immunotherapy for the treatment of melanoma, version 3.0. Journal For ImmunoTherapy Of Cancer 2023, 11: e006947. PMID: 37852736, PMCID: PMC10603365, DOI: 10.1136/jitc-2023-006947.Peer-Reviewed Original ResearchConceptsImmune checkpoint inhibitorsClinical practice guidelinesCutaneous melanomaTreatment of melanomaPractice guidelinesProlongs recurrence-free survivalCancer clinical practice guidelinesCell death protein 1Metastatic cutaneous melanomaBispecific T cell engager (BiTE) therapyChemotherapy-resistant diseaseRecurrence-free survivalDeath protein 1Long-term followManagement of patientsSpecial patient populationsImmunotherapy of cancerConsensus-based recommendationsPossibility of cureUnique toxicity profileQuality of lifeIntratumoral immunotherapyNeoadjuvant strategiesAdvanced diseaseBrain metastasesA 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, Muñoz-Couselo E, Rodríguez-Abreu D, Boni V, Schuchter L, Cao M, Fernandez 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 cellsCheckMate-915: does adjuvant CTLA-4 blockade play a role in resected melanoma?
Su D, Kluger H, Weiss S. CheckMate-915: does adjuvant CTLA-4 blockade play a role in resected melanoma? Annals Of Translational Medicine 2023, 0: 0-0. PMID: 37675335, PMCID: PMC10477634, DOI: 10.21037/atm-23-754.Peer-Reviewed Original ResearchCombinatorial Immunotherapy with Agonistic CD40 Activates Dendritic Cells to Express IL12 and Overcomes PD-1 Resistance.
Krykbaeva I, Bridges K, Damsky W, Pizzurro G, Alexander A, McGeary M, Park K, Muthusamy V, Eyles J, Luheshi N, Turner N, Weiss S, Olino K, Kaech S, Kluger H, Miller-Jensen K, Bosenberg M. Combinatorial Immunotherapy with Agonistic CD40 Activates Dendritic Cells to Express IL12 and Overcomes PD-1 Resistance. Cancer Immunology Research 2023, 11: 1332-1350. PMID: 37478171, DOI: 10.1158/2326-6066.cir-22-0699.Peer-Reviewed Original ResearchConceptsPD-1 resistanceDendritic cellsTumor regressionAnti-PD-1 resistanceActivates Dendritic CellsCytokine secretion profilingSystemic cytokine profileTriple therapy combinationInnate immune activationAdaptive immune responsesComplete tumor regressionMajority of miceSignificant clinical challengeMouse melanoma modelT cell activationAgonistic CD40Checkpoint inhibitorsDC subsetsTriple therapyCytokine profileImmune activationCombinatorial immunotherapyTherapy combinationsT cellsClinical challengeCase 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 durationPatientsCarcinomaA phase 2/3 trial in progress on tebentafusp as monotherapy and in combination with pembrolizumab in HLA-A*02:01+ patients with previously treated advanced non-uveal melanoma (TEBE-AM).
Davar D, Ikeguchi A, Buchbinder E, Shoushtari A, Seedor R, Bernicker E, Weiss S, Daniels G, Panella T, Ryan H, Goodall H, Sullivan R. A phase 2/3 trial in progress on tebentafusp as monotherapy and in combination with pembrolizumab in HLA-A*02:01+ patients with previously treated advanced non-uveal melanoma (TEBE-AM). Journal Of Clinical Oncology 2023, 41: tps9594-tps9594. DOI: 10.1200/jco.2023.41.16_suppl.tps9594.Peer-Reviewed Original ResearchMetastatic cutaneous melanomaMetastatic uveal melanomaAdvanced melanomaInvestigator's choicePrimary endpointDual primary endpointsOverall survival benefitPhase 3 trialSimilar patient populationsPhase 2/3 trialIC armOS benefitPrior ipilimumabRECIST responseInhibitor regimenSupportive careSurvival benefitCare therapyAnti-CTLA4CtDNA levelsTumor burdenInvestigational agentsPatient populationCutaneous melanomaClinical trialsThe role of imaging and sentinel lymph node biopsy in patients with T3b-T4b melanoma with clinically negative disease
Papageorge M, Maina R, King A, Lee V, Baumann R, Pucar D, Ariyan S, Khan S, Weiss S, Clune J, Olino K. The role of imaging and sentinel lymph node biopsy in patients with T3b-T4b melanoma with clinically negative disease. Frontiers In Oncology 2023, 13: 1143354. PMID: 37223678, PMCID: PMC10200883, DOI: 10.3389/fonc.2023.1143354.Peer-Reviewed Original ResearchPre-operative imagingCross-sectional imagingFree survivalLow-risk melanomaHigh-risk melanomaHigh-risk diseaseKaplan-Meier methodRecurrence-free survivalSentinel node biopsyWide local excisionManagement of patientsLog-rank testRole of imagingPropensity-score matchingIncidental cancerT4b diseaseMetastatic diseaseNodal diseaseNode biopsyPerioperative periodMedian ageNegative diseaseSentinel lymphLocal excisionNodular melanomaLenvatinib or anti-VEGF in combination with anti-PD-1 differentially augments anti-tumor activity in melanoma
Tran T, Caulfield J, Zhang L, Schoenfeld D, Djureinovic D, Chiang V, Oria V, Weiss S, Olino K, Jilaveanu L, Kluger H. Lenvatinib or anti-VEGF in combination with anti-PD-1 differentially augments anti-tumor activity in melanoma. JCI Insight 2023, 8: e157347. PMID: 36821392, PMCID: PMC10132152, DOI: 10.1172/jci.insight.157347.Peer-Reviewed Original ResearchConceptsTumor microenvironmentAnti-VEGFCytokine/chemokine signalingCytokine/chemokine profilingBlood-brain barrier modelBlood vesselsLeukocyte transmigrationTumor-associated blood vesselsTumor-associated macrophagesIntratumoral blood vesselsAnti-angiogenesis effectAnti-tumor activityExtracranial diseasePlasmacytoid DCsImmune checkpointsPD-1Melanoma murine modelImmune infiltrationBBB modelChemokine profilingEndothelial stabilizationMurine modelLenvatinibCombined targetingMelanoma model
2021
389 Phase II of CD40 agonistic antibody sotigalimab (APX005M) in combination with nivolumab in subjects with metastatic melanoma with confirmed disease progression on anti-PD-1 therapy
Weiss S, Sznol M, Shaheen M, Berciano-Guerrero M, Felip E, Rodríguez-Abreu D, Arance A, Boni V, Linette G, Schuchter L, Gonzalez-Cao M, Iannotti N, Ganti A, Hauke R, Berrocal A, Filbert E, Kluger H. 389 Phase II of CD40 agonistic antibody sotigalimab (APX005M) in combination with nivolumab in subjects with metastatic melanoma with confirmed disease progression on anti-PD-1 therapy. Journal For ImmunoTherapy Of Cancer 2021, 9: a422-a422. DOI: 10.1136/jitc-2021-sitc2021.389.Peer-Reviewed Original ResearchAnti-PD-1 therapyMelanoma patientsMetastatic melanomaTumor PD-L1 expressionEffective anti-tumor immunityArm phase II trialCD40 agonist antibodyRefractory melanoma patientsRefractory metastatic melanomaAdvanced melanoma patientsPD-1 blockadePD-L1 expressionPhase II trialAnti-tumor immunitySubset of patientsOverall safety profileMajority of AEsOptimal therapeutic applicationReceptor binding profileInstitutional review boardClinical study teamNebraska Medical CenterOpen labelII trialTolerability profileIncidence and characteristics of metastatic intracranial lesions in stage III and IV melanoma: a single institute retrospective analysis
Sandhu MRS, Chiang VL, Tran T, Yu JB, Weiss S, Goldberg S, Aboian M, Kluger HM, Mahajan A. Incidence and characteristics of metastatic intracranial lesions in stage III and IV melanoma: a single institute retrospective analysis. Journal Of Neuro-Oncology 2021, 154: 197-203. PMID: 34351544, DOI: 10.1007/s11060-021-03813-8.Peer-Reviewed Original ResearchConceptsStage IV melanomaMetastatic brain lesionsStage IIIInitial diagnosisTumor RegistryOverall incidenceBrain lesionsBM incidenceSingle-institute retrospective analysisBM developmentBrain metastases incidenceIncidence of BMInstitution's tumor registryStage III patientsTime of diagnosisMetastatic intracranial lesionsCommon genetic mutationsTumor genetic profileGenetic profileBM occurrenceMedian durationAdvanced melanomaSurveillance regimenIII patientsMedian time
2020
Melanoma brain metastases have lower T-cell content and microvessel density compared to matched extracranial metastases
Weiss SA, Zito C, Tran T, Heishima K, Neumeister V, McGuire J, Adeniran A, Kluger H, Jilaveanu LB. Melanoma brain metastases have lower T-cell content and microvessel density compared to matched extracranial metastases. Journal Of Neuro-Oncology 2020, 152: 15-25. PMID: 32974852, PMCID: PMC7910371, DOI: 10.1007/s11060-020-03619-0.Peer-Reviewed Original ResearchConceptsT-cell contentMelanoma brain metastasesPD-L1 expressionLower microvessel densityMicrovessel densityBrain metastasesExtracranial metastasesMacrophage contentB cellsProspective therapeutic clinical trialsTumor-infiltrating T cellsImmune-modulating drugsImmune cell subsetsTherapeutic clinical trialsExtracerebral metastasesHigh CD68Low CD3Low CD8Systemic therapyIntracerebral metastasesMetastatic sitesCell subsetsMetastatic melanomaImmune cellsClinical trials19. PLEKHA5 REGULATES TUMOR GROWTH IN METASTATIC MELANOMA
Oria V, Zhang H, Zhu H, Deng G, Zito C, Rane C, Zhang S, Weiss S, Tran T, Adeniran A, Zhang F, Zhou J, Kluger Y, Bosenberg M, Kluger H, Jilaveanu L. 19. PLEKHA5 REGULATES TUMOR GROWTH IN METASTATIC MELANOMA. Neuro-Oncology Advances 2020, 2: ii3-ii3. PMCID: PMC7401364, DOI: 10.1093/noajnl/vdaa073.009.Peer-Reviewed Original ResearchMelanoma brain metastasesBrain metastasesTumor growthPI3K/Akt/mTORCell cycle transitionAkt/mTORGrowth of tumorsS cell cycle transitionPhosphorylation of AktMelanoma patientsPoor prognosisNovel drug targetsPatient populationRegulation of PDCD4Metastatic melanomaUnique cohortXenograft modelClinical relevanceNude miceMetastasisCycle transitionMelanomaBrain developmentKey mediatorMelanoma cellsSystemic Therapy for Brain Metastases: Melanoma
Weiss S, Kluger H. Systemic Therapy for Brain Metastases: Melanoma. 2020, 235-244. DOI: 10.1007/978-3-030-42958-4_16.Peer-Reviewed Original ResearchMelanoma brain metastasesIntracranial response ratesBrain metastasesClinical trialsResponse rateAnti-PD-1 monotherapyCentral nervous system metastasesExtracranial metastatic sitesNervous system metastasesSystemic therapy approachesMultiple clinical trialsSystemic therapySystemic treatmentAdvanced melanomaImmune checkpointsMetastatic sitesTherapeutic challengePatient survivalMetastatic melanomaExtracranial sitesStereotactic radiosurgeryMetastasisMutant BRAFSignificant causeMEK inhibitionNeoadjuvant anti–programmed cell death 1 therapy for locally advanced basal cell carcinoma in treatment-naive patients: A case series
Ligtenberg KG, Hu JK, Damsky W, Olino K, Kluger H, Clune J, Cowper SE, Panse G, Leventhal J, Weiss SA. Neoadjuvant anti–programmed cell death 1 therapy for locally advanced basal cell carcinoma in treatment-naive patients: A case series. JAAD Case Reports 2020, 6: 628-633. PMID: 32613057, PMCID: PMC7317689, DOI: 10.1016/j.jdcr.2020.05.010.Peer-Reviewed Case Reports and Technical NotesSurvival after checkpoint inhibitors for metastatic acral, mucosal and uveal melanoma
Klemen ND, Wang M, Rubinstein JC, Olino K, Clune J, Ariyan S, Cha C, Weiss SA, Kluger HM, Sznol M. Survival after checkpoint inhibitors for metastatic acral, mucosal and uveal melanoma. Journal For ImmunoTherapy Of Cancer 2020, 8: e000341. PMID: 32209601, PMCID: PMC7103823, DOI: 10.1136/jitc-2019-000341.Peer-Reviewed Original ResearchConceptsCheckpoint inhibitorsOverall survivalMetastatic melanomaPrimary tumorLocal therapyCutaneous melanomaAnti-PD-1 antibodyAggressive multidisciplinary approachCutaneous primary tumorPrimary tumor histologyMedian overall survivalSingle institutional experienceRare melanoma subtypeMedian OSMetastatic diseaseProgressive diseaseAcral skinComplete responsePD-1PD-L1Uveal tractTumor histologyCombination therapyCTLA-4Longer survivalPrognostic and Predictive Biomarkers in Oligometastatic Disease.
Barnum KJ, Weiss SA. Prognostic and Predictive Biomarkers in Oligometastatic Disease. The Cancer Journal 2020, 26: 100-107. PMID: 32205533, PMCID: PMC9208067, DOI: 10.1097/ppo.0000000000000438.Peer-Reviewed Original ResearchMeSH KeywordsAntineoplastic Combined Chemotherapy ProtocolsBiomarkers, TumorCirculating Tumor DNAClinical Decision-MakingDisease-Free SurvivalHumansMicroRNAsMutationNeoplasmsNeoplastic Cells, CirculatingPatient SelectionPrognosisProgression-Free SurvivalRadiofrequency AblationRadiosurgeryRisk AssessmentSurvival RateConceptsLocal therapyOligometastatic diseaseSystemic therapyPredictive biomarkersCurative-intent local therapyAdvanced disease stateCancer-related deathSurvival benefitPatient candidatesMetastatic lesionsPatient selectionPoor prognosisAblative treatmentClinical definitionTumor biologyTherapyOligometastasesDisease statesDiseasePatientsLocal interventionsBiomarkersPolymetastasesPrognosisLesions
2019
Immune Checkpoint Inhibitor Therapy in Patients With Preexisting Inflammatory Bowel Disease
Abu-Sbeih H, Faleck DM, Ricciuti B, Mendelsohn RB, Naqash AR, Cohen JV, Sellers MC, Balaji A, Ben-Betzalel G, Hajir I, Zhang J, Awad MM, Leonardi GC, Johnson DB, Pinato DJ, Owen DH, Weiss SA, Lamberti G, Lythgoe MP, Manuzzi L, Arnold C, Qiao W, Naidoo J, Markel G, Powell N, Yeung SJ, Sharon E, Dougan M, Wang Y. Immune Checkpoint Inhibitor Therapy in Patients With Preexisting Inflammatory Bowel Disease. Journal Of Clinical Oncology 2019, 38: 576-583. PMID: 31800340, PMCID: PMC7030892, DOI: 10.1200/jco.19.01674.Peer-Reviewed Original ResearchConceptsGI adverse eventsInflammatory bowel diseaseImmune checkpoint inhibitor therapyCheckpoint inhibitor therapyImmune checkpoint inhibitorsAdverse eventsCheckpoint inhibitorsBowel diseaseInhibitor therapyAnti-cytotoxic T-lymphocyte antigen-4 therapyTreatment of IBDCytotoxic T-lymphocyte antigen-4T-lymphocyte antigen-4Cell death 1Multivariate logistic regressionImmunotherapy initiationColonic perforationGI eventsDeath-1Ulcerative colitisCrohn's diseaseMedian timeMultivariable analysisRetrospective studySimilar patients