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, 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 timeLifileucel (LN-144), a cryopreserved autologous tumor infiltrating lymphocyte (TIL) therapy in patients with advanced melanoma: Evaluation of impact of prior anti-PD-1 therapy.
Larkin J, Sarnaik A, Chesney J, Khushalani N, Kirkwood J, Weber J, Lewis K, Medina T, Kluger H, Thomas S, Domingo-Musibay E, Olah J, Whitman E, Martin-Algarra S, Corrie P, Lutzky J, Shi W, Wu R, Fardis M, Hamid O. Lifileucel (LN-144), a cryopreserved autologous tumor infiltrating lymphocyte (TIL) therapy in patients with advanced melanoma: Evaluation of impact of prior anti-PD-1 therapy. Journal Of Clinical Oncology 2021, 39: 9505-9505. DOI: 10.1200/jco.2021.39.15_suppl.9505.Peer-Reviewed Original ResearchAnti-PD-1 therapyPrior anti-PD-1 therapyObjective response rateImmune checkpoint inhibitorsAdvanced melanomaPrimary resistanceAnti-PD-1 resistanceAnti-PD-1 responseBaseline tumor burdenDays of cyclophosphamideDays of fludarabineMedian cumulative durationMedian prior linesLong-term followAdoptive cell therapyStandard of careDetection of progressionNew safety risksDuration of exposureAutologous tumorMelanoma progressPrior therapyRECIST 1.1TIL productionCheckpoint inhibitorsLifileucel, a Tumor-Infiltrating Lymphocyte Therapy, in Metastatic Melanoma
Sarnaik AA, Hamid O, Khushalani NI, Lewis KD, Medina T, Kluger HM, Thomas SS, Domingo-Musibay E, Pavlick AC, Whitman ED, Martin-Algarra S, Corrie P, Curti BD, Oláh J, Lutzky J, Weber JS, Larkin JMG, Shi W, Takamura T, Jagasia M, Qin H, Wu X, Chartier C, Finckenstein F, Fardis M, Kirkwood JM, Chesney JA. Lifileucel, a Tumor-Infiltrating Lymphocyte Therapy, in Metastatic Melanoma. Journal Of Clinical Oncology 2021, 39: 2656-2666. PMID: 33979178, PMCID: PMC8376325, DOI: 10.1200/jco.21.00612.Peer-Reviewed Original ResearchConceptsObjective response rateDisease control rateAdvanced melanomaPrimary refractoryControl rateMetastatic melanomaTreatment optionsInterleukin-2Investigator-assessed objective response rateHigh-dose interleukin-2Tumor-Infiltrating Lymphocyte TherapyImmune checkpoint inhibitorsPrimary end pointTumor-infiltrating lymphocytesEffective treatment optionLimited treatment optionsAdoptive cell therapyMajor unmet needLymphodepletion regimenPrior therapyCheckpoint inhibitorsAdverse eventsDurable responsesMedian durationPartial responseProlonged Complete Response of Early Stage Primary Adenocarcinoma of the Lung to Nivolumab Monotherapy.
Unlu S, Grant MJ, Gettinger S, Adeniran A, Kluger HM. Prolonged Complete Response of Early Stage Primary Adenocarcinoma of the Lung to Nivolumab Monotherapy. Clinical Oncology Case Reports 2021, 4 PMID: 34382032, PMCID: PMC8353529.Peer-Reviewed Original ResearchMultiple primary malignant tumorsNivolumab monotherapyCheckpoint inhibitorsLung cancerHigh Programmed-Death Ligand 1 (PD-L1) expressionProgrammed Death Ligand 1 ExpressionNon-small cell lung cancerMultiple regional lymph nodesImmune checkpoint inhibitorsPD-1 inhibitorsLigand 1 expressionPrimary lung cancerEarly-stage diseaseRegional lymph nodesCell lung cancerPrimary malignant tumorsHigh-risk natureSystemic immunotherapyDurable responsesAdvanced melanomaComplete responseEffective immunotherapyLymph nodesMore patientsPrimary adenocarcinoma
2020
Systemic 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 inhibitionLong-term follow up of lifileucel (LN-144) cryopreserved autologous tumor infiltrating lymphocyte therapy in patients with advanced melanoma progressed on multiple prior therapies.
Sarnaik A, Khushalani N, Chesney J, Lewis K, Medina T, Kluger H, Thomas S, Domingo Musibay E, Pavlick A, Whitman E, Martin-Algarra S, Corrie P, Lutzky J, Hamid O, Wu R, Shi W, Fardis M, Weber J, Larkin J, Kirkwood J. Long-term follow up of lifileucel (LN-144) cryopreserved autologous tumor infiltrating lymphocyte therapy in patients with advanced melanoma progressed on multiple prior therapies. Journal Of Clinical Oncology 2020, 38: 10006-10006. DOI: 10.1200/jco.2020.38.15_suppl.10006.Peer-Reviewed Original ResearchBRAF/MEK inhibitorsMultiple prior therapiesMedian DoRPrior therapyCheckpoint inhibitorsAdvanced melanomaMelanoma patientsMedian studyMEK inhibitorsBaseline tumor burdenCohort 2 patientsIL-2 regimensAdverse event profileLong-term followMetastatic melanoma patientsIL-2 dosesAdoptive cell therapyUnresectable metastatic melanomaBaseline disease burdenBody's natural defensesAnti-cancer therapyAutologous tumorRECIST v1.1TIL productionAdvanced disease