2025
Long-term Efficacy and Safety of Lifileucel Tumor-infiltrating Lymphocyte (TIL) Cell Therapy in Patients with Advanced Melanoma: A 5-year Analysis of the C-144-01 Study.
Medina T, Chesney J, Kluger H, Hamid O, Whitman E, Cusnir M, Thomas S, Wermke M, Domingo-Musibay E, Phan G, Kirkwood J, Larkin J, Weber J, Graf Finckenstein F, Chou J, Gastman B, Wu X, Fiaz R, Sarnaik A, Curti B, Kim K, Daniels G, Wilson M, Lee S, Puzanov I, Harker-Murray A, Logan T, Simon J, Thomas I, Schuler-Thurner B, Moritz R, Hassel J, Grigoliet G, Arance A, Rubio B, Rodriguez J, Berrocal A, de Sanmamed M, Arkenau H, Evans T, Corrie P, Dalle S, Bedane C, Olah J, Orcurto A. Long-term Efficacy and Safety of Lifileucel Tumor-infiltrating Lymphocyte (TIL) Cell Therapy in Patients with Advanced Melanoma: A 5-year Analysis of the C-144-01 Study. Journal Of Clinical Oncology 2025, 101200jco2500765. PMID: 40454684, DOI: 10.1200/jco-25-00765.Peer-Reviewed Original ResearchTumor-infiltrating lymphocytesOverall survivalLong-term efficacyCell therapyMedian duration of responseLow tumor burdenMedian overall survivalDuration of responseTumor burden reductionLong-term safety concernsBRAF/MEK inhibitorsAdvanced melanomaBrain metastasesImmune checkpointsTumor burdenMedian durationSafety profileAdverse eventsTreatment optionsInterleukin-2Follow-upLong-term benefitsOverall populationPatientsCutoff dateLifileucel in patients with advanced melanoma: 5-year outcomes of the C-144-01 study.
Medina T, Chesney J, Kluger H, Hamid O, Whitman E, Cusnir M, Thomas S, Wermke M, Domingo-Musibay E, Phan G, Kirkwood J, Larkin J, Weber J, Finckenstein F, Chou J, Gastman B, Sulur G, Wu R, Fiaz R, Sarnaik A. Lifileucel in patients with advanced melanoma: 5-year outcomes of the C-144-01 study. Journal Of Clinical Oncology 2025, 43: 9515-9515. DOI: 10.1200/jco.2025.43.16_suppl.9515.Peer-Reviewed Original ResearchDuration of responseAnti-PD-1/PD-L1 therapyAdvanced melanomaFollow-upOverall survivalEastern Cooperative Oncology Group performance statusAnti-PD-1/PD-L1Autologous T-cell immunotherapyMedian duration of responseTreatment-emergent adverse eventsDoses of interleukin-2Treatment of adult patientsImmune checkpoint inhibitorsT-cell immunotherapyTumor-infiltrating lymphocytesDurability of responseLong-term safety concernsOpen-label studyStudy follow-upGroup of ptsMedian OSRefractory melanomaCheckpoint inhibitorsOS ratesRECIST v1.1Role of high-dose interleukin-2 for melanoma in the age of cellular therapy
Buchbinder E, Lotze M, Margolin K, Amaria R, Sarnaik A, Seery V, Eroglu Z, Khaddour K, Warner A, Kluger H, Sznol M, Atkins M, Mcdermott D, Silk A. Role of high-dose interleukin-2 for melanoma in the age of cellular therapy. Journal For ImmunoTherapy Of Cancer 2025, 13: e011119. PMID: 40447314, PMCID: PMC12128428, DOI: 10.1136/jitc-2024-011119.Peer-Reviewed Original ResearchConceptsTumor-infiltrating lymphocytesTIL infusionInterleukin-2Cellular therapyHigh-dose bolus IL-2High-dose interleukin-2Renal cell carcinoma patientsBolus interleukin-2Cytokine-related toxicitiesExcellent organ functionIL-2 monotherapyIL-2 toxicityLife-threatening side effectsPartial tumor regressionCell carcinoma patientsInterleukin-2 dosesT cell productionTreatment of patientsNational Cancer InstituteAdvanced melanomaTumor regressionCarcinoma patientsAdjunctive therapyInpatient administrationSide effectsMicroglial reprogramming: a potential new frontier in enhancing immunotherapy for melanoma brain metastasis
Savion‐Gaiger N, Bar‐Ziv D, Kluger H. Microglial reprogramming: a potential new frontier in enhancing immunotherapy for melanoma brain metastasis. Molecular Oncology 2025, 19: 1291-1294. PMID: 40111148, PMCID: PMC12077281, DOI: 10.1002/1878-0261.70028.Peer-Reviewed Original ResearchConceptsMelanoma brain metastasesBrain metastasesSites of metastatic disseminationHuman brain metastasesAdvanced melanomaEnhance immunotherapyMurine studiesTumor microenvironmentMetastatic disseminationMyeloid cellsMelanoma cellsMelanomaMetastasisMicroglial cellsPotential new frontiersCellsBrainImmunotherapyTumorMicroenvironmentReal-world outcomes with T-VEC in patients with anti-PD-1 resistant in-transit disease from melanoma and Merkel cell carcinoma
Su D, McNamara M, Kaszycki M, Frey A, Ishizuka J, Costa P, Tran T, Kluger H, Clune J, Weiss S, Olino K. Real-world outcomes with T-VEC in patients with anti-PD-1 resistant in-transit disease from melanoma and Merkel cell carcinoma. Surgical Oncology Insight 2025, 2: 100120. DOI: 10.1016/j.soi.2024.100120.Peer-Reviewed Original ResearchMerkel cell carcinomaMerkel cell carcinoma casesT-VECCell carcinomaMedian numberAnti-PD-1 blockadeStage IIIB-IV melanomaAdvanced Merkel cell carcinomaIn-transit melanomaIn-transit diseaseICI therapyTalimogene laherparepvecAdvanced melanomaCancer immunotherapyMetastatic sitesPartial responseIn-transitRegional metastasesMedian ageGrade 3Adverse eventsTreatment cyclesDisease progressionMelanomaPatients
2024
Causes of death and patterns of metastatic disease at the end of life for patients with advanced melanoma in the immunotherapy era
Lee D, McNamara M, Yang A, Yaskolko M, Kluger H, Tran T, Olino K, Clune J, Sznol M, Ishizuka J. Causes of death and patterns of metastatic disease at the end of life for patients with advanced melanoma in the immunotherapy era. Pigment Cell & Melanoma Research 2024, 37: 847-853. PMID: 39073002, PMCID: PMC11809125, DOI: 10.1111/pcmr.13188.Peer-Reviewed Original ResearchSite of metastasisPattern of metastatic diseaseMelanoma mortalityRetrospective observational cohort studyCause of cancer mortalityDistant lymph nodesObservational cohort studyDiagnosis to deathImmunotherapy eraAdvanced melanomaMetastatic diagnosisMetastatic diseaseMetastatic melanomaImmunotherapy treatmentRespiratory failureCause of deathMedian timeLymph nodesTherapeutic advancesCohort studyMelanomaImmunotherapyMechanism of deathPatientsEnd of lifeCauses of death and patterns of metastatic disease at the end of life for patients with advanced melanoma in the immunotherapy era.
Lee D, Yang A, McNamara M, Kluger H, Tran T, Olino K, Clune J, Sznol M, Ishizuka J. Causes of death and patterns of metastatic disease at the end of life for patients with advanced melanoma in the immunotherapy era. Journal Of Clinical Oncology 2024, 42: e21522-e21522. DOI: 10.1200/jco.2024.42.16_suppl.e21522.Peer-Reviewed Original ResearchImmune checkpoint inhibitorsYale Cancer CenterAdvanced melanomaMetastatic diseaseMetastatic melanomaRespiratory failureSite of metastatic diseasePattern of metastatic diseaseDied of respiratory failureAnti-CTLA4 treatmentRetrospective observational cohort studyAnti-PD1 therapyDistant lymph nodesPatients aged >Site of diseaseSurvival of patientsObservational cohort studyMulti-system involvementDiagnosis to deathImmunotherapy eraAnti-PD1Checkpoint inhibitorsInstitutional review boardMetastatic sitesMetastatic diagnosis
2023
119O Long-term efficacy and patterns of response of lifileucel tumor-infiltrating lymphocyte (TIL) cell therapy in patients with advanced melanoma: A 4-year analysis of the C-144-01 study
Medina T, Chesney J, Whitman E, Kluger H, Thomas S, Sarnaik A, Kirkwood J, Larkin J, Weber J, Hamid O, Wermke M, Finckenstein F, Chou J, Gastman B, Sulur G, Wu X, Shi W, Domingo-Musibay E. 119O Long-term efficacy and patterns of response of lifileucel tumor-infiltrating lymphocyte (TIL) cell therapy in patients with advanced melanoma: A 4-year analysis of the C-144-01 study. Immuno-Oncology Technology 2023, 20: 100591. DOI: 10.1016/j.iotech.2023.100591.Peer-Reviewed Original Research776 Long-term efficacy and safety of lifileucel tumor-infiltrating lymphocyte (TIL) cell therapy in patients with advanced melanoma: a 4-year analysis of the C-144–01 study
Medina T, Chesney J, Whitman E, Kluger H, Thomas S, Sarnaik A, Kirkwood J, Larkin J, Weber J, Hamid O, Wermke M, Finckenstein F, Chou J, Gastman B, Sulur G, Wu X, Shi W, Domingo-Musibay E. 776 Long-term efficacy and safety of lifileucel tumor-infiltrating lymphocyte (TIL) cell therapy in patients with advanced melanoma: a 4-year analysis of the C-144–01 study. 2023, a873-a873. DOI: 10.1136/jitc-2023-sitc2023.0776.Peer-Reviewed Original ResearchA 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 cellsIL-7R licenses a population of epigenetically poised memory CD8+ T cells with superior antitumor efficacy that are critical for melanoma memory
Micevic G, Daniels A, Flem-Karlsen K, Park K, Talty R, McGeary M, Mirza H, Blackburn H, Sefik E, Cheung J, Hornick N, Aizenbud L, Joshi N, Kluger H, Iwasaki A, Bosenberg M, Flavell R. IL-7R licenses a population of epigenetically poised memory CD8+ T cells with superior antitumor efficacy that are critical for melanoma memory. Proceedings Of The National Academy Of Sciences Of The United States Of America 2023, 120: e2304319120. PMID: 37459511, PMCID: PMC10372654, DOI: 10.1073/pnas.2304319120.Peer-Reviewed Original ResearchConceptsIL-7R expressionT cellsIL-7RAntitumor memorySuperior antitumor efficacyCell-based therapiesTumor-specific T cellsAntigen-specific T cellsAntitumor efficacyPowerful antitumor immune responseMarkers of exhaustionTumor-specific CD8Antitumor immune responseIndependent prognostic factorAntitumor immune memoryMemory T cellsMajor risk factorSuperior antitumor activityFunctional CD8Memory CD8Prognostic factorsSurgical resectionAdvanced melanomaLymph nodesNaive miceSurvival, Durable Tumor Remission, and Long-Term Safety in Patients With Advanced Melanoma Receiving Nivolumab
Topalian S, Sznol M, McDermott D, Kluger H, Carvajal R, Sharfman W, Brahmer J, Lawrence D, Atkins M, Powderly J, Leming P, Lipson E, Puzanov I, Smith D, Taube J, Wigginton J, Kollia G, Gupta A, Pardoll D, Sosman J, Hodi F. Survival, Durable Tumor Remission, and Long-Term Safety in Patients With Advanced Melanoma Receiving Nivolumab. Journal Of Clinical Oncology 2023, 41: 943-954. PMID: 36750016, DOI: 10.1200/jco.22.02272.Peer-Reviewed Original ResearchLong-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-1290 Response to Lifileucel Tumor-Infiltrating Lymphocyte (TIL) Cell Therapy after ICI Resistance Regardless of Definition: An Analysis of the C-144-01 Trial in Patients with Advanced Melanoma
Sarnaik A, Chesney J, Medina T, Hamid O, Thomas S, Wermke M, Gontcharova V, Damirchi B, Dean J, Mastellar E, Wu X, Shi W, Kluger H. 290 Response to Lifileucel Tumor-Infiltrating Lymphocyte (TIL) Cell Therapy after ICI Resistance Regardless of Definition: An Analysis of the C-144-01 Trial in Patients with Advanced Melanoma. Transplantation And Cellular Therapy 2023, 29: s223-s224. DOI: 10.1016/s2666-6367(23)00359-7.Peer-Reviewed Original Research
2022
Baseline gene expression profiling determines long-term benefit to programmed cell death protein 1 axis blockade
Vathiotis I, Salichos L, Martinez-Morilla S, Gavrielatou N, Aung T, Shafi S, Wong P, Jessel S, Kluger H, Syrigos K, Warren S, Gerstein M, Rimm D. Baseline gene expression profiling determines long-term benefit to programmed cell death protein 1 axis blockade. Npj Precision Oncology 2022, 6: 92. PMID: 36522538, PMCID: PMC9755314, DOI: 10.1038/s41698-022-00330-3.Peer-Reviewed Original ResearchProgression-free survivalLong-term benefitsPredictive valueAnti-PD-1 therapyCell death protein 1Baseline tumor samplesImmune checkpoint inhibitorsAntitumor immune responseCohort of patientsDeath protein 1Gene expression profilesAdvanced diseaseCheckpoint inhibitorsAdvanced melanomaAxis blockadeImmunotherapy outcomesTreatment initiationEarly outcomesDisease progressionMalignant melanomaBaseline gene expressionImmune responseBaseline gene expression profilesExpression profilesTumor samples35MO Number of IL-2 doses and clinical outcomes of tumor-infiltrating lymphocyte (TIL) cell therapy: Post hoc analysis of the C-144-01 trial of lifileucel in patients with advanced melanoma
Hassel J, Sarnaik A, Chesney J, Medina T, Hamid O, Thomas S, Wermke M, Domingo-Musibay E, Kirkwood J, Larkin J, Weber J, Fernandez A, Rodriguez J, Thomas I, Corrie P, Gontcharova V, Wu X, Shi W, Kluger H. 35MO Number of IL-2 doses and clinical outcomes of tumor-infiltrating lymphocyte (TIL) cell therapy: Post hoc analysis of the C-144-01 trial of lifileucel in patients with advanced melanoma. Immuno-Oncology Technology 2022, 16: 100140. DOI: 10.1016/j.iotech.2022.100140.Peer-Reviewed Original Research789 Lifileucel TIL cell monotherapy in patients with advanced melanoma after progression on immune checkpoint inhibitors (ICI) and targeted therapy: pooled analysis of consecutive cohorts (C-144–01 study)
Sarnaik A, Lewis K, Kluger H, Hamid O, Whitman E, Thomas S, Wermke M, Cusnir M, Domingo-Musibay E, Phan G, Kirkwood J, Hassel J, Orloff M, Larkin J, Weber J, Furness A, Khushalani N, Medina T, Finckenstein F, Jagasia M, Hari P, Sulur G, Shi W, Wu X, Chesney J. 789 Lifileucel TIL cell monotherapy in patients with advanced melanoma after progression on immune checkpoint inhibitors (ICI) and targeted therapy: pooled analysis of consecutive cohorts (C-144–01 study). 2022, a821-a822. DOI: 10.1136/jitc-2022-sitc2022.0789.Peer-Reviewed Original Research844P Efficacy and safety of lifileucel, an investigational autologous tumor-infiltrating lymphocyte (TIL) cell therapy, in patients with advanced melanoma previously treated with anti-LAG3 antibody
Larkin J, Dalle S, Sanmamed M, Wilson M, Hassel J, Kluger H, Orloff M, Weber J, Finckenstein F, Hari P, Jagasia M, Yin H, Shi W, Sulur G, Wu X, Gontcharova V, Lewis K. 844P Efficacy and safety of lifileucel, an investigational autologous tumor-infiltrating lymphocyte (TIL) cell therapy, in patients with advanced melanoma previously treated with anti-LAG3 antibody. Annals Of Oncology 2022, 33: s935-s936. DOI: 10.1016/j.annonc.2022.07.970.Peer-Reviewed Original ResearchTumor mutational burden (TMB) in immune checkpoint inhibitor (ICI)-naïve and -experienced patients with metastatic melanoma treated with lifileucel, a tumor-infiltrating lymphocyte (TIL) cell therapy.
Kluger H, Sarnaik A, Chesney J, Lewis K, Weber J, Gogas H, In G, Terheyden P, Lee S, Jagasia M, Masteller E, Qi R, Gontcharova V, Shi W, Fiaz R, Sulur G, Wu R, Chen G, Thomas S. Tumor mutational burden (TMB) in immune checkpoint inhibitor (ICI)-naïve and -experienced patients with metastatic melanoma treated with lifileucel, a tumor-infiltrating lymphocyte (TIL) cell therapy. Journal Of Clinical Oncology 2022, 40: 9524-9524. DOI: 10.1200/jco.2022.40.16_suppl.9524.Peer-Reviewed Original ResearchHigh tumor mutational burdenObjective response rateTumor mutational burdenCase-control studyAdvanced melanomaMetastatic melanomaTumor harvestResponse rateCell therapyT cell receptor repertoireLymphocyte cell therapyTumor microenvironment profilesImmune checkpoint inhibitorsPercentage of patientsTreatment of patientsHigh TMB groupMut/MbLogistic regression analysisICI exposureICI therapyRECIST v1.1Checkpoint inhibitorsStudy entryTMB groupBRAF statusInhibition of renalase drives tumour rejection by promoting T cell activation
Guo X, Jessel S, Qu R, Kluger Y, Chen TM, Hollander L, Safirstein R, Nelson B, Cha C, Bosenberg M, Jilaveanu LB, Rimm D, Rothlin CV, Kluger HM, Desir GV. Inhibition of renalase drives tumour rejection by promoting T cell activation. European Journal Of Cancer 2022, 165: 81-96. PMID: 35219026, PMCID: PMC8940682, DOI: 10.1016/j.ejca.2022.01.002.Peer-Reviewed Original ResearchConceptsPD-1 inhibitorsMurine melanoma modelMelanoma-bearing miceMelanoma modelTumor microenvironmentTumor rejectionCell death protein 1 (PD-1) inhibitorsAnti-PD-1 activityEnhanced T cell infiltrationT cell-dependent fashionMelanoma cellsMelanoma tumor regressionPreclinical melanoma modelsT cell infiltrationNatural killer cellsForkhead box P3Expression of IFNγWild-type miceProtein 1 inhibitorT cell activationTumor cell contentWild-type melanoma cellsCD4 cellsAdvanced melanomaAntibody treatment
2021
Incidence 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
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