2024
Targeting STAT3 in tumor-associated antigen-presenting cells as a strategy for kidney and bladder cancer immunotherapy
Alcantara M, Tang W, Wang D, Kaniowski D, Kang E, Dizman N, Chehrazi-Raffle A, Meza L, Zengin Z, Hall J, Hsu J, Egelston C, Moreira D, Horsager A, Pal S, Kortylewski M. Targeting STAT3 in tumor-associated antigen-presenting cells as a strategy for kidney and bladder cancer immunotherapy. Frontiers In Immunology 2024, 14: 1274781. PMID: 38259453, PMCID: PMC10800835, DOI: 10.3389/fimmu.2023.1274781.Peer-Reviewed Original ResearchImmune checkpoint blockadeDendritic cellsCancer patientsBladder cancerT cellsTumor-associated antigen-presenting cellsTherapeutic efficacyLesser extent IL-10T cell-based immunotherapyImmune checkpoint inhibitorsTumor immune evasionAntitumor immune responseCD8 T cellsRegulatory T cellsBladder cancer immunotherapyCell-based immunotherapyAntigen-presenting cellsSTAT3 activationRenal cancer patientsBladder cancer patientsImmune cell activityMyeloid immune cellsICB resistanceIpilimumab immunotherapyCheckpoint inhibitors
2023
Real-World Outcomes of Latinx Versus Non-Latinx Patients Treated With First-Line Immunotherapy for Metastatic Renal-Cell Carcinoma
Chehrazi-Raffle A, Leong S, Ali S, Kim T, Melamed S, Li X, Zengin Z, Meza L, Chawla N, Govindarajan A, Castro D, Mercier B, Ebrahimi H, Dizman N, Tripathi N, Sayegh N, Rock A, Yeh J, Pal S, Onyshchenko M. Real-World Outcomes of Latinx Versus Non-Latinx Patients Treated With First-Line Immunotherapy for Metastatic Renal-Cell Carcinoma. The Oncologist 2023, 28: 1079-1084. PMID: 37432304, PMCID: PMC10712704, DOI: 10.1093/oncolo/oyad190.Peer-Reviewed Original ResearchConceptsMetastatic renal cell carcinomaProgression-free survivalComprehensive cancer centerNivolumab/ipilimumabShorter progression-free survivalOverall survivalRenal cell carcinomaLatinx patientsMultivariate Cox proportional hazards regressionCox proportional hazards regressionSafety-net healthcare systemHope Comprehensive Cancer CenterFirst-line immunotherapyTertiary oncology centerImmune checkpoint inhibitorsLos Angeles County DepartmentMedian overall survivalKaplan-Meier methodProportional hazards regressionDifferent healthcare settingsReal-world outcomesCheckpoint inhibitorsData cutoffClinical outcomesHazards regressionEffect of CBM588 in combination with cabozantinib plus nivolumab for patients (pts) with metastatic renal cell carcinoma (mRCC): A randomized clinical trial.
Ebrahimi H, Meza L, Lee K, Malhotra J, Alcantara M, Zengin Z, Dizman N, Govindarajan A, Hsu J, Llamas-Quitiquit M, Chawla N, Castro D, Mercier B, Liu S, Chehrazi-Raffle A, Dorff T, Frankel P, Li X, Pal S, Tripathi A. Effect of CBM588 in combination with cabozantinib plus nivolumab for patients (pts) with metastatic renal cell carcinoma (mRCC): A randomized clinical trial. Journal Of Clinical Oncology 2023, 41: lba104-lba104. DOI: 10.1200/jco.2023.41.17_suppl.lba104.Peer-Reviewed Original ResearchMetastatic renal cell carcinomaProgression-free survivalTyrosine kinase inhibitorsPrimary endpointClinical outcomesStool specimensDual immune checkpoint inhibitorsMedian progression-free survivalImproved progression-free survivalOne-sided type I errorBifidobacterium sppGrade 3/4 toxicitiesImmune checkpoint inhibitorsStudy's primary endpointWeeks of treatmentDose/scheduleRandomized clinical trialsRenal cell carcinomaEligible ptsPo bidSystemic immunomodulationCheckpoint inhibitorsSecondary endpointsLine therapyMetastatic diseaseChanges in Perception of Cure Among Patients With Genitourinary Cancers Initiating Immune Checkpoint Inhibitors: A Longitudinal Study
Bergerot C, Philip E, Govindarajan A, Castro D, Malhotra J, Bergerot P, Salgia S, Salgia M, Salgia N, Hsu J, Meza L, Zengin Z, Liu S, Chehrazi-Raffle A, Tripathi A, Dorff T, Pal S. Changes in Perception of Cure Among Patients With Genitourinary Cancers Initiating Immune Checkpoint Inhibitors: A Longitudinal Study. Clinical Genitourinary Cancer 2023, 21: 626-630.e3. PMID: 37391301, PMCID: PMC11225089, DOI: 10.1016/j.clgc.2023.05.018.Peer-Reviewed Original ResearchConceptsPerception of cureExpectation of cureGenitourinary cancersImmune checkpoint inhibitor therapyCheckpoint inhibitor therapyImmune checkpoint inhibitorsProportion of patientsSevere side effectsLongitudinal studyChi-square testICI therapyCheckpoint inhibitorsInhibitor therapyECOG scoreGeneral linear modelingPatients' perceptionsMetastatic cancerPatientsSide effectsDecreased anxietyTherapyCancerCureLower ratesAnxiety Scale
2022
Genomic and Clinical Prognostic Factors in Patients With Advanced Urothelial Carcinoma Receiving Immune Checkpoint Inhibitors
Chawla N, Sayegh N, Tripathi N, Govindarajan A, Zengin Z, Phillip E, Dizman N, Meza L, Muddasani R, Chehrazi-Raffle A, Malhotra J, Hsu J, Agarwal N, Pal S, Tripathi A. Genomic and Clinical Prognostic Factors in Patients With Advanced Urothelial Carcinoma Receiving Immune Checkpoint Inhibitors. Clinical Genitourinary Cancer 2022, 21: 69-75. PMID: 36509613, DOI: 10.1016/j.clgc.2022.11.007.Peer-Reviewed Original ResearchConceptsProgression-free survivalOverall response rateTumor mutational burdenOverall survivalWorse OSPrimary diseaseMultivariate analysisMedian progression-free survivalImmune checkpoint inhibitor therapyInferior progression-free survivalPromoter mutationsWorse progression-free survivalCheckpoint inhibitor therapyMedian overall survivalImmune checkpoint inhibitorsTertiary cancer centerClinical prognostic factorsPrimary tumor siteTERT promoter mutationsCheckpoint inhibitorsInhibitor therapyLaboratory parametersPrognostic factorsCancer CenterFemale sex880 Activation of STAT3 signaling is associated with resistance to immune checkpoint inhibitors in patients (pts) with metastatic renal cell carcinoma (mRCC)
Chehrazi-Raffle A, Alcantara M, Dizman N, Tang W, Meza L, Zengin Z, Wang D, Moreira D, Castro D, Govindarajan A, Horsager A, Hsu J, Pal S, Kortylewski M. 880 Activation of STAT3 signaling is associated with resistance to immune checkpoint inhibitors in patients (pts) with metastatic renal cell carcinoma (mRCC). 2022, a917-a917. DOI: 10.1136/jitc-2022-sitc2022.0880.Peer-Reviewed Original ResearchNivolumab plus ipilimumab with or without live bacterial supplementation in metastatic renal cell carcinoma: a randomized phase 1 trial
Dizman N, Meza L, Bergerot P, Alcantara M, Dorff T, Lyou Y, Frankel P, Cui Y, Mira V, Llamas M, Hsu J, Zengin Z, Salgia N, Salgia S, Malhotra J, Chawla N, Chehrazi-Raffle A, Muddasani R, Gillece J, Reining L, Trent J, Takahashi M, Oka K, Higashi S, Kortylewski M, Highlander SK, Pal SK. Nivolumab plus ipilimumab with or without live bacterial supplementation in metastatic renal cell carcinoma: a randomized phase 1 trial. Nature Medicine 2022, 28: 704-712. PMID: 35228755, PMCID: PMC9018425, DOI: 10.1038/s41591-022-01694-6.Peer-Reviewed Original ResearchConceptsMetastatic renal cell carcinomaProgression-free survivalRenal cell carcinomaCell carcinomaCheckpoint inhibitorsResponse rateGut microbiomePoor-risk diseaseTreatment-naive patientsSingle-center studyPhase 1 trialRandomized phase 1 trialSignificant differencesBifidobacterium sppMechanism of actionNivolumab-ipilimumabSarcomatoid histologyPrimary endpointSecondary endpointsImmune compartmentStudy armsClinical outcomesClear cellsClinical observationsPatientsWaning efficacy of COVID-19 vaccination at six months in patients (pts) with genitourinary malignancies.
Zengin Z, Meza L, Malhotra J, Salgia S, Ely J, Hsu J, Kelley E, Mead H, Dizman N, Chehrazi-Raffle A, Govindarajan A, Muddasani R, Chawla N, Dorff T, Lyou Y, Karczewska E, Trent J, Salgia R, Altin J, Pal S. Waning efficacy of COVID-19 vaccination at six months in patients (pts) with genitourinary malignancies. Journal Of Clinical Oncology 2022, 40: 185-185. DOI: 10.1200/jco.2022.40.6_suppl.185.Peer-Reviewed Original ResearchCOVID-19 vaccinationBlood samplesSystemic treatmentAntibody titersGenitourinary malignanciesSubset of ptsImmune checkpoint inhibitorsBaseline blood samplesLong-term efficacyAdditional blood samplesCOVID-19 vaccineSARS-CoV-2Short-term effectivenessCancer ptsSerologic outcomeCheckpoint inhibitorsGenitourinary cancersMedian ageTherapy cyclesBladder cancerTCR sequencingIgG ELISACoV-2Host immunityVaccinationAssociation between TERT promoter mutations and clinical outcome with immune checkpoint inhibitor therapy for advanced urothelial cancer.
Chawla N, Tripathi N, Sayegh N, Govindarajan A, Dizman N, Zengin Z, Meza L, Muddasani R, Chehrazi-Raffle A, Salgia S, Malhotra J, Hsu J, Philip E, Bergerot C, Lyou Y, Swami U, Gupta S, Maughan B, Agarwal N, Pal S. Association between TERT promoter mutations and clinical outcome with immune checkpoint inhibitor therapy for advanced urothelial cancer. Journal Of Clinical Oncology 2022, 40: 561-561. DOI: 10.1200/jco.2022.40.6_suppl.561.Peer-Reviewed Original ResearchProgression-free survivalObjective response rateImmune checkpoint inhibitorsICI therapyOverall survivalTERT promoter mutationsBladder cancerFirst-line ICI therapyImmune checkpoint inhibitor therapyAdvanced urothelial cancerSubsequent-line therapyUpper tract diseaseCheckpoint inhibitor therapySuperior overall survivalMetastatic bladder cancerMuscle-invasive diseaseTertiary cancer centerRoutine clinical careCancer Genome Atlas (TCGA) databaseLarge independent cohortsPromoter mutationsTERT mutation statusCheckpoint inhibitorsMetastatic settingVariant histologyAssociation of intra-tumoral microbiome and response to immune checkpoint inhibitors (ICIs) in patients with metastatic renal cell carcinoma (mRCC).
Meza L, Choi Y, Govindarajan A, Dizman N, Zengin Z, Hsu J, Salgia N, Salgia S, Malhotra J, Chawla N, Chehrazi-Raffle A, Muddasani R, Castro D, Chan A, Zhang G, Byron S, Highlander S, Schork N, Pal S. Association of intra-tumoral microbiome and response to immune checkpoint inhibitors (ICIs) in patients with metastatic renal cell carcinoma (mRCC). Journal Of Clinical Oncology 2022, 40: 372-372. DOI: 10.1200/jco.2022.40.6_suppl.372.Peer-Reviewed Original ResearchMetastatic renal cell carcinomaImmune checkpoint inhibitorsClear cell histologyFirst-line treatmentRoutine clinical careRenal cell carcinomaT-testPaucity of dataStudent's t-testParaffin-embedded samplesICI respondersICI therapyCheckpoint inhibitorsCell histologyClinical responseOverall cohortLine treatmentImmunotherapeutic agentsCell carcinomaPoor riskSpecific bacteriaLarge cohortClinical careICI activityPrimary sitePredictive Biomarkers of Immunotherapy Efficacy in RCC and Their Role in Non-metastatic Stages
Malhotra J, Meza L, Salgia N, Pal S. Predictive Biomarkers of Immunotherapy Efficacy in RCC and Their Role in Non-metastatic Stages. 2022, 221-227. DOI: 10.1007/978-3-030-80546-3_17.ChaptersManagement of metastatic renal cell carcinomaProgrammed death-ligand 1Renal cell carcinomaMedian survivalCell carcinomaMetastatic renal cell carcinomaDeath-ligand 1Non-metastatic stageCheckpoint inhibitorsImmunotherapy efficacySequence therapyPredictive biomarkersInterleukin-2Exploratory markersClinical practiceCarcinomaClinical judgmentSurvivalBiomarkersPrognosisTherapyPatientsEfficacy
2021
Targeted therapies: Expanding the role of FGFR3 inhibition in urothelial carcinoma
Zengin Z, Chehrazi-Raffle A, Salgia N, Muddasani R, Ali S, Meza L, Pal S. Targeted therapies: Expanding the role of FGFR3 inhibition in urothelial carcinoma. Urologic Oncology Seminars And Original Investigations 2021, 40: 25-36. PMID: 34840077, DOI: 10.1016/j.urolonc.2021.10.003.Peer-Reviewed Original ResearchConceptsImmune checkpoint inhibitorsUrothelial carcinomaCheckpoint inhibitorsTargeted therapyLower tract diseaseMultiple disease stagesMetastatic urothelial carcinomaOverall response rateAntibody-drug conjugatesGrowth factor receptor familyFGFR3 inhibitionUC tumorsChemotherapy regimensUpper tractOngoing trialsDisease stageTract diseaseTreatment paradigmFactor receptor familyHigh incidenceActionable mutationsFGFR1-4FGFR3 inhibitorsSmall molecule inhibitorsFGFR3 mutationsThe impact of antibiotic (Ab) exposure on clinical outcomes in patients with metastatic renal cell carcinoma (mRCC) treated with immune checkpoint inhibitors (ICI) or VEGF targeted therapy (VEGF-TT).
Ernst M, Alaiwi S, Dizman N, Labaki C, Nuzzo P, Adib E, Schmidt A, Meza L, Gan C, Wells J, Bakouny Z, Pal S, Choueiri T, Heng D, Dudani S. The impact of antibiotic (Ab) exposure on clinical outcomes in patients with metastatic renal cell carcinoma (mRCC) treated with immune checkpoint inhibitors (ICI) or VEGF targeted therapy (VEGF-TT). Journal Of Clinical Oncology 2021, 39: 4552-4552. DOI: 10.1200/jco.2021.39.15_suppl.4552.Peer-Reviewed Original ResearchMetastatic renal cell carcinomaImmune checkpoint inhibitorsOverall survivalABS exposureClinical outcomesTreatment failureResponse rateMultivariable analysisIndependent associationRisk factorsAdministration of AbFourth-line settingIMDC risk factorsIMDC risk scoresPoor-risk diseaseTreatment linesMultivariable Cox regressionInferior clinical outcomesInferior overall survivalIndependent prognostic markerRenal cell carcinomaSignificant independent associationOutcomes of interestIMDC criteriaCheckpoint inhibitorsCirculating cytokines associated with clinical response to systemic therapy in metastatic renal cell carcinoma
Chehrazi-Raffle A, Meza L, Alcantara M, Dizman N, Bergerot P, Salgia N, Hsu J, Ruel N, Salgia S, Malhotra J, Karczewska E, Kortylewski M, Pal S. Circulating cytokines associated with clinical response to systemic therapy in metastatic renal cell carcinoma. Journal For ImmunoTherapy Of Cancer 2021, 9: e002009. PMID: 33688021, PMCID: PMC7944971, DOI: 10.1136/jitc-2020-002009.Peer-Reviewed Original ResearchConceptsVascular endothelial growth factor tyrosine kinase inhibitorMetastatic renal cell carcinomaRenal cell carcinomaImmune checkpoint inhibitorsColony-stimulating factorClinical benefitPlasma cytokinesSystemic therapyCell carcinomaInterleukin-6Prospective correlative studyLines of therapyLow pretreatment levelsGranulocyte colony-stimulating factorGranulocyte-macrophage colony-stimulating factorRCC histologic subtypesMacrophage colony-stimulating factorICI armsICI therapyStable diseaseCheckpoint inhibitorsClinical responsePartial responseComplete responseImmunologic profileDistinct cytokines predict response to immunotherapy and targeted therapy in metastatic renal cell carcinoma (mRCC).
Chehrazi-Raffle A, Meza L, Alcantara M, Salgia N, Dizman N, Bergerot P, Hsu J, Kortylewski M, Pal S. Distinct cytokines predict response to immunotherapy and targeted therapy in metastatic renal cell carcinoma (mRCC). Journal Of Clinical Oncology 2021, 39: 352-352. DOI: 10.1200/jco.2021.39.6_suppl.352.Peer-Reviewed Original ResearchVascular endothelial growth factor tyrosine kinase inhibitorMetastatic renal cell carcinomaImmune checkpoint inhibitorsPlasma cytokinesClinical benefitCommon immune checkpoint inhibitorsICI combination therapyLow pretreatment levelsRenal cell carcinomaEligible patientsICI armsStable diseaseCheckpoint inhibitorsImmunologic profilePartial responseSystemic therapyComplete responseProspective studyIL-1raCell carcinomaCombination therapyIL-6Pretreatment levelsDistinct cytokinesG-CSF
2020
Immune Related Adverse Events: Classification and Management Approaches in Advanced Kidney Cancer.
Zengin Z, Salgia N, Chehrazi-Raffle A, Meza L, Malhotra J, Pal S. Immune Related Adverse Events: Classification and Management Approaches in Advanced Kidney Cancer. The Cancer Journal 2020, 26: 432-440. PMID: 32947311, DOI: 10.1097/ppo.0000000000000473.Peer-Reviewed Original ResearchConceptsImmune checkpoint inhibitorsMetastatic renal cell carcinomaRenal cell carcinomaCheckpoint inhibitorsAdverse eventsCell carcinomaDeath ligand 1 (PD-L1) immune checkpoint inhibitorsAnti-programmed death-1/Common immune-related adverse eventsImmune-related adverse eventsPivotal phase III trialsPrevious treatment optionsPhase III trialsDeath-1/Advanced kidney cancerRecent therapeutic advancementsUnique toxicity profileDrug Administration approvalFrontline regimensIII trialsClinical outcomesTreatment optionsRare toxicityAdministration approvalTargeted therapy