2024
77 Impact of CBM588 on gut microbiome composition and dysbiosis in patients receiving frontline immune checkpoint inhibitor (ICI) combinations for metastatic renal cell carcinoma (mRCC)
Dizman N, Ebrahimi H, Barragan-Carrillo R, Meza L, Bergerot P, Dorff T, BSc J, Zengin Z, Castro D, Chehrazi-Raffle A, Triphathi A, Trent J, Takahashi M, Oka K, Higashi S, Caporaso G, Lee K, Pal S. 77 Impact of CBM588 on gut microbiome composition and dysbiosis in patients receiving frontline immune checkpoint inhibitor (ICI) combinations for metastatic renal cell carcinoma (mRCC). The Oncologist 2024, 29: s5-s5. PMCID: PMC11301884, DOI: 10.1093/oncolo/oyae181.007.Peer-Reviewed Original ResearchMetastatic renal cell carcinomaImmune checkpoint inhibitorsStandard of careGut microbiome compositionStandard of care cohortMicrobiome compositionGut dysbiosisClinical outcomesClinically relevant microbial speciesCompared gut microbiome diversityCell metastatic renal cell carcinomaRandomized phase I clinical trialClinically relevant speciesAssociated with ICI responseStandard of care regimensRelevant microbial speciesGut microbiome diversityRatio of Firmicutes/BacteroidetesPhase I clinical trialPhase III studyBaseline to weekAnalyzed stool samplesFirst-line treatmentRenal cell carcinomaBeta diversityCabozantinib and nivolumab with or without live bacterial supplementation in metastatic renal cell carcinoma: a randomized phase 1 trial
Ebrahimi H, Dizman N, Meza L, Malhotra J, Li X, Dorff T, Frankel P, Llamas-Quitiquit M, Hsu J, Zengin Z, Alcantara M, Castro D, Mercier B, Chawla N, Chehrazi-Raffle A, Barragan-Carrillo R, Jaime-Casas S, Govindarajan A, Gillece J, Trent J, Lee P, Parks T, Takahashi M, Hayashi A, Kortylewski M, Caporaso J, Lee K, Tripathi A, Pal S. Cabozantinib and nivolumab with or without live bacterial supplementation in metastatic renal cell carcinoma: a randomized phase 1 trial. Nature Medicine 2024, 30: 2576-2585. PMID: 38942995, PMCID: PMC11405272, DOI: 10.1038/s41591-024-03086-4.Peer-Reviewed Original ResearchMetastatic renal cell carcinomaProgression-free survivalRenal cell carcinomaCell carcinomaToxicity profileAbundance of Bifidobacterium sppControl armTreatment-naive participantsFirst-line treatmentPhase 1 studyPhase 1 trialSarcomatoid componentOpen-labelHistological confirmationPrimary endpointSecondary endpointsNo significant differenceClear cellNivolumabInvestigator-initiatedClinical outcomesCabozantinibClinical activityStool samplesStudy armsImpact of CBM588 on gut microbiome composition and dysbiosis in patients receiving frontline immune checkpoint inhibitor (ICI) combinations for metastatic renal cell carcinoma (mRCC).
Dizman N, Ebrahimi H, Barragán Carrillo R, Meza L, Bergerot P, Dorff T, Hsu J, Zengin Z, Castro D, Chehrazi-Raffle A, Tripathi A, Trent J, Takahashi M, Oka K, Higashi S, Caporaso G, Lee K, Pal S. Impact of CBM588 on gut microbiome composition and dysbiosis in patients receiving frontline immune checkpoint inhibitor (ICI) combinations for metastatic renal cell carcinoma (mRCC). Journal Of Clinical Oncology 2024, 42: 4550-4550. DOI: 10.1200/jco.2024.42.16_suppl.4550.Peer-Reviewed Original ResearchMetastatic renal cell carcinomaImmune checkpoint inhibitorsStandard of careStandard of care cohortGut microbiome compositionMicrobiome compositionClinical outcomesCell metastatic renal cell carcinomaRandomized phase I clinical trialGut dysbiosisAssociated with ICI responseStandard of care regimensClinically relevant microbial speciesCompared gut microbiome diversityPhase I clinical trialClinically relevant speciesPhase III studyRelevant microbial speciesBaseline to weekFirst-line treatmentGut microbiome diversityRatio of Firmicutes/BacteroidetesRenal cell carcinomaWilcoxon matched pairs testAnalyzed stool samplesPrevalence of Dietary Modification and Supplement Use in Patients with Metastatic Renal Cell Carcinoma Receiving Systemic Therapy
Ebrahimi H, Battle D, Salgia N, Zengin Z, Dizman N, Meza L, Bergerot C, Barragan-Carrillo R, Hsu J, Castro D, Mercier B, Chawla N, Li X, Tripathi A, Liu S, Chehrazi-Raffle A, Vaishampayan U, Staehler M, Pal S. Prevalence of Dietary Modification and Supplement Use in Patients with Metastatic Renal Cell Carcinoma Receiving Systemic Therapy. Nutrients 2024, 16: 1630. PMID: 38892563, PMCID: PMC11174627, DOI: 10.3390/nu16111630.Peer-Reviewed Original ResearchMetastatic renal cell carcinomaRenal cell carcinomaCell carcinomaDietary modificationSupplement useDiagnosis of renal cell carcinomaFirst-line treatmentSupplement usageSystemic therapyCombination therapyAntineoplastic therapyKetogenic dietCarcinomaCancer therapyMediterranean dietPhysician-patient dialoguePatientsTherapyCancer treatmentGrowing body of evidenceBody of evidenceDietary changesCancerCancer diagnosisCannabidiolCombination nivolumab and ipilimumab with and without camu camu in first-line treatment of metastatic renal cell carcinoma (mRCC).
Barragan-Carrillo R, Chawla N, Salgia N, Meza L, Zengin Z, Li X, Dizman N, Ebrahimi H, Hsu J, Castro D, Mercier B, Dorff T, Tripathi A, Bergerot C, Bergerot P, Chehrazi-Raffle A, Pal S. Combination nivolumab and ipilimumab with and without camu camu in first-line treatment of metastatic renal cell carcinoma (mRCC). Journal Of Clinical Oncology 2024, 42: tps491-tps491. DOI: 10.1200/jco.2024.42.4_suppl.tps491.Peer-Reviewed Original ResearchMetastatic renal cell carcinomaImmune checkpoint inhibitionBaseline to weekFirst-line treatmentClinical responsePoor-risk metastatic renal cell carcinomaFirst-line treatment of metastatic renal cell carcinomaTreatment of metastatic renal cell carcinomaCombination of immune checkpoint inhibitionEfficacy of anti-PD1 therapyCombination immune checkpoint inhibitionDual immune checkpoint inhibitionCD8+ T cellsAnti-PD1 therapyImmune-related toxicitiesProgression-free survivalWeeks of therapyReduced tumor sizeTyrosine kinase inhibitorsSingle-center trialRenal cell carcinomaClear-cell RCCMouse tumor modelsOne-sided type I errorCombination nivolumab
2023
Genomic and Transcriptomic Characteristics of Tumors of Patients with Metastatic Clear Cell Renal Cell Carcinoma Clinically Benefiting from First-Line Treatment with Ipilimumab Plus Nivolumab
Tripathi N, Meza L, Sayegh N, Govindarajan A, Byron S, Zhang J, Chigarira B, Jo Y, Zengin Z, Li H, Gebrael G, Desai A, Agarwal N, Swami U, Maughan B, Pal S. Genomic and Transcriptomic Characteristics of Tumors of Patients with Metastatic Clear Cell Renal Cell Carcinoma Clinically Benefiting from First-Line Treatment with Ipilimumab Plus Nivolumab. Kidney Cancer 2023, 7: 137-145. DOI: 10.3233/kca-230011.Peer-Reviewed Original ResearchMetastatic renal cell carcinomaClear cell metastatic renal cell carcinomaClinical benefit groupRenal cell carcinomaClinical benefitNivolumab therapyCell carcinomaPoor-risk metastatic renal cell carcinomaMetastatic clear cell renal cell carcinomaBenefit groupClear cell renal cell carcinomaFirst-line ipilimumabIMDC risk scoresFirst-line treatmentCell renal cell carcinomaAlteration frequencyChi-square testMRCC patientsStable diseaseComplete responsePartial responseSystemic therapyLine treatmentInflammatory pathwaysTumor-specific gene expressionImpact of Time to Metastasis (Synchronous vs. Metachronous) on Outcomes in Metastatic Renal Cell Carcinoma Patients Treated with First Line Immune-Checkpoint Inhibitors (ICI)-based Combinations
Meza L, Li X, Zengin Z, Sayegh N, Ebrahimi H, Tripathi N, Castro D, Mercier B, Barragan-Carrillo R, Li H, Chehrazi-Raffle A, Swami U, Tripathi A, Agarwal N, Maughan B, Pal S. Impact of Time to Metastasis (Synchronous vs. Metachronous) on Outcomes in Metastatic Renal Cell Carcinoma Patients Treated with First Line Immune-Checkpoint Inhibitors (ICI)-based Combinations. The Oncologist 2023, 28: s9-s10. PMCID: PMC10445590, DOI: 10.1093/oncolo/oyad216.014.Peer-Reviewed Original ResearchDisease control rateFirst-line ICIImmune checkpoint inhibitorsOverall survivalTime of presentationSynchronous diseaseTreatment failureRenal cell carcinomaMetachronous diseaseMetastatic diseaseRCC diagnosisFirst-line immune checkpoint inhibitorsMetastatic renal cell carcinoma patientsMultivariable Cox proportional hazards modelsLower disease control rateNon-clear cell histologyMetastatic renal cell carcinomaRenal cell carcinoma patientsCox proportional hazards modelIMDC risk scoresInitial RCC diagnosisSynchronous metastatic diseaseMedian overall survivalMedian TTFFirst-line treatmentThe impact of insurance status on progression-free survival (PFS) and overall survival (OS) in patients with metastatic renal cell carcinoma (mRCC)
Castro D, Tripathi N, Sayegh N, Gebrael G, Li X, Meza L, Zengin Z, Chehrazi-Raffle A, Govindarajan A, Dizman N, Ebrahimi H, Chawla N, Mercier B, BS J, Shi J, Philip E, Bergerot C, Barragan-Carrillo R, Pal S. The impact of insurance status on progression-free survival (PFS) and overall survival (OS) in patients with metastatic renal cell carcinoma (mRCC). The Oncologist 2023, 28: s5-s6. PMCID: PMC10445577, DOI: 10.1093/oncolo/oyad216.008.Peer-Reviewed Original ResearchMetastatic renal cell carcinomaMedian progression-free survivalProgression-free survivalLog-rank testMedian overall survivalOverall survivalMedicaid/Insurance statusSecondary insurancePrivate insurancePrimary insuranceSystemic therapyClinical outcomesEntire cohortInferior median progression-free survivalSuperior median progression-free survivalSignificant differencesCox proportional hazards regression modelFirst-line systemic therapyMedicaid/uninsured patientsSuperior progression-free survivalProportional hazards regression modelsLine systemic therapyFirst-line treatmentKaplan-Meier methodPrevalence of dietary modification and supplement use in patients with metastatic renal cell carcinoma (mRCC).
Ebrahimi H, Battle D, Zengin Z, Dizman N, Meza L, Castro D, Govindarajan A, Mercier B, Chawla N, Chehrazi-Raffle A, Tripathi A, Liu S, Vaishampayan U, Staehler M, Pal S. Prevalence of dietary modification and supplement use in patients with metastatic renal cell carcinoma (mRCC). Journal Of Clinical Oncology 2023, 41: 662-662. DOI: 10.1200/jco.2023.41.6_suppl.662.Peer-Reviewed Original ResearchMetastatic renal cell carcinomaRenal cell carcinomaDietary modificationSupplement useCell carcinomaSupplement intakeKetogenic dietSupplement usageActive systemic therapyNivolumab/ipilimumabFirst-line treatmentMajority of patientsT-testPatient advocacy groupsChi-square testStudent's t-testClinical trial candidatesOnly patientsSystemic therapyMedian ageAntineoplastic treatmentProspective studyPotential confoundersInclusion criteriaMediterranean dietOutcomes for International Metastatic Renal Cell Carcinoma Database Consortium Prognostic Groups in Contemporary First-line Combination Therapies for Metastatic Renal Cell Carcinoma
Ernst M, Navani V, Wells J, Donskov F, Basappa N, Labaki C, Pal S, Meza L, Wood L, Ernst D, Szabados B, McKay R, Parnis F, Suarez C, Yuasa T, Lalani A, Alva A, Bjarnason G, Choueiri T, Heng D. Outcomes for International Metastatic Renal Cell Carcinoma Database Consortium Prognostic Groups in Contemporary First-line Combination Therapies for Metastatic Renal Cell Carcinoma. European Urology 2023, 84: 109-116. PMID: 36707357, DOI: 10.1016/j.eururo.2023.01.001.Peer-Reviewed Original ResearchConceptsInternational mRCC Database ConsortiumMetastatic renal cell carcinomaInternational mRCC Database Consortium risk groupIO combination therapyIpi-nivoOverall survivalRenal cell carcinomaCombination therapyTreatment durationRisk groupsCell carcinomaImmuno-oncologyTreatment cohortsInternational Metastatic Renal Cell Carcinoma Database Consortium modelStandard of care first-line treatmentVascular endothelial growth factor-targeted therapyFirst-line combination therapyMedian follow-up timePoor-risk groupEndpoint of OSFirst-line treatmentKaplan-Meier methodLog-rank testModel stratified patientsShort follow-upGenomic and Transcriptomic Predictors of Response from Stereotactic Body Radiation Therapy in Patients with Oligoprogressive Renal Cell Carcinoma
Zengin Z, Govindarajan A, Salgia N, Sayegh N, Tripathi N, Muddasani R, Chehrazi-Raffle A, Feng M, Mercier B, Ladbury C, Hao C, Salgia S, Chawla N, Meza L, Malhotra J, Dizman N, Hsu J, Castro D, Barragan-Carrillo R, Ebrahimi H, Philip E, Chang M, Zhang J, Byron S, Lyou Y, Dorff T, Pal S, Dandapani S. Genomic and Transcriptomic Predictors of Response from Stereotactic Body Radiation Therapy in Patients with Oligoprogressive Renal Cell Carcinoma. European Urology Oncology 2023, 6: 447-450. PMID: 36609061, DOI: 10.1016/j.euo.2022.11.006.Peer-Reviewed Original ResearchConceptsMetastatic renal cell carcinomaStereotactic body radiation therapyRenal cell carcinomaBody radiation therapyCell carcinomaRadiation therapyClear cell renal cell carcinomaFirst-line treatmentCell renal cell carcinomaStereotactic body radiotherapyKidney cancer patientsOligoprogressive diseaseSystemic treatmentReactive oxygen species pathwayBody radiotherapyCancer patientsTreatment selectionPatientsTreatment changesOxygen species pathwayRadiation treatmentCarcinomaCell proliferationPotential roleRadiotherapy
2022
A phase I trial to evaluate the biologic effect of CBM588 (Clostridium butyricum) in combination with cabozantinib plus nivolumab for patients with metastatic renal cell carcinoma (mRCC).
Meza L, Malhotra J, Zengin Z, Dizman N, Hsu J, Chawla N, Chehrazi-Raffle A, Muddasani R, Govindarajan A, Castro D, Dorff T, Lyou Y, Frankel P, Pal S. A phase I trial to evaluate the biologic effect of CBM588 (Clostridium butyricum) in combination with cabozantinib plus nivolumab for patients with metastatic renal cell carcinoma (mRCC). Journal Of Clinical Oncology 2022, 40: tps4606-tps4606. DOI: 10.1200/jco.2022.40.16_suppl.tps4606.Peer-Reviewed Original ResearchMetastatic renal cell carcinomaClinical responseClear cell metastatic renal cell carcinomaTyrosine kinase inhibitor cabozantinibBiologic effectsGut microbiomeImmune checkpoint inhibitor nivolumabOne-sided type I errorPhase I clinical trialFirst-line treatmentProgression-free survivalStudy's primary endpointCheckpoint inhibitor nivolumabPhase I trialPhase 1 trialSubgroup of patientsWeeks of treatmentCytokines/chemokinesDose/scheduleOngoing phase IRenal cell carcinomaImproved clinical benefitBifidobacterium sppEligible patientsPo bidIntestinal microbiome associated with development of grade 3/4 adverse in patients with metastatic renal cell carcinoma (mRCC) treated with nivolumab plus ipilimumab (N/I) and probiotic support: Results from a phase Ib study.
Meza L, Dizman N, Bergerot P, Dorff T, Lyou Y, Frankel P, Llamas M, Hsu J, Zengin Z, Salgia N, Malhotra J, Chawla N, Gillece J, Reining L, Trent J, Takahashi M, Oka K, Higashi S, Highlander S, Pal S. Intestinal microbiome associated with development of grade 3/4 adverse in patients with metastatic renal cell carcinoma (mRCC) treated with nivolumab plus ipilimumab (N/I) and probiotic support: Results from a phase Ib study. Journal Of Clinical Oncology 2022, 40: 374-374. DOI: 10.1200/jco.2022.40.6_suppl.374.Peer-Reviewed Original ResearchMetastatic renal cell carcinomaSetting of mRCCStool microbiome compositionPhase Ib studyWeeks of therapyFirst-line treatmentLung cancer patientsRenal cell carcinomaMicrobiome compositionDevelopment of treatmentsB. thetaiotamicronMedian followMRCC patientsAdverse eventsData cutoffOverall cohortIntervention armLine treatmentCell carcinomaCancer patientsTRAEsStool samplesStool specimensIntestinal microbiomeLarge cohortAssociation 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 siteCharacterizing IMDC prognostic groups in contemporary first-line combination therapies for metastatic renal cell carcinoma (mRCC).
Ernst M, Navani V, Wells J, Donskov F, Basappa N, Labaki C, Pal S, Meza L, Wood L, Ernst D, Szabados B, McKay R, Parnis F, Suárez C, Yuasa T, Kapoor A, Alva A, Bjarnason G, Choueiri T, Heng D. Characterizing IMDC prognostic groups in contemporary first-line combination therapies for metastatic renal cell carcinoma (mRCC). Journal Of Clinical Oncology 2022, 40: 308-308. DOI: 10.1200/jco.2022.40.6_suppl.308.Peer-Reviewed Original ResearchInternational mRCC Database ConsortiumMetastatic renal cell carcinomaVascular endothelial growth factor-targeted therapyIpi-nivoImmuno-oncology agentsOverall survivalCombination therapyComplete responseFirst-lineFirst-line treatment of metastatic renal cell carcinomaTreatment of metastatic renal cell carcinomaInternational mRCC Database Consortium criteriaClinical trialsFirst-line combination therapyEfficacy of combination therapyNon-clear cell histologyTherapy to deathFirst-line treatmentLog-rank testRenal cell carcinomaReal-world survivalCell histologySarcomatoid featuresOS outcomesLiver metastases