2024
Immune Landscape and Outcomes of Patients with RNA Splicing Factor-Mutant Acute Myeloid Leukemia and Myelodysplastic Syndromes Treated with Azacitidine +/- the Anti-PD-L1 Antibody Durvalumab
Bewersdorf J, Hasle V, Shallis R, Thompson E, De Menezes D, Rose S, Boss I, Mendez L, Podoltsev N, Stahl M, Kewan T, Halene S, Haferlach T, Fox B, Zeidan A. Immune Landscape and Outcomes of Patients with RNA Splicing Factor-Mutant Acute Myeloid Leukemia and Myelodysplastic Syndromes Treated with Azacitidine +/- the Anti-PD-L1 Antibody Durvalumab. Blood 2024, 144: 4585. DOI: 10.1182/blood-2024-194929.Peer-Reviewed Original ResearchAcute myeloid leukemiaAnti-PD-L1 antibody durvalumabOverall response rateMyelodysplastic syndromeComplete responseBM aspiratesMyeloid leukemiaInternational Working GroupBone marrowMyelodysplastic syndromes treated with azacitidineAcute myeloid leukemia ptsWild-type acute myeloid leukemiaSecondary acute myeloid leukemiaResponse criteriaAnti-PD-L1Immune checkpoint inhibitorsTreated with azacitidineOutcomes of patientsAny-cause deathGeneration of neoantigensVariant allele frequencySusceptible to treatmentMarrow CRAdverse cytogeneticsCheckpoint inhibitorsMitochondrial Heteroplasmy Is a Novel Predictor of Chronic Lymphocytic Leukemia Risk
Pasca S, Hong Y, Shi W, Puiu D, Lake N, Lek M, Guallar E, Arking D, Gondek L. Mitochondrial Heteroplasmy Is a Novel Predictor of Chronic Lymphocytic Leukemia Risk. Blood 2024, 144: 4054-4054. DOI: 10.1182/blood-2024-210250.Peer-Reviewed Original ResearchMitochondrial heteroplasmyClonal hematopoiesis of indeterminate potentialMtDNA heteroplasmyWhole-exome sequencing dataSomatic mutationsPresence of somatic mutationsExome sequencing dataCancer-associated genesClonal hematopoiesisClonal expansionVariant allele frequencyAssociated with myeloid malignanciesMtDNA variantsMitochondrial DNAPresence of mutationsSequence dataUK Biobank (UKBBiologically significant roleDeleterious mutationsHeteroplasmyChronic lymphocytic leukemia riskAllele frequenciesOncogenic transformationMitochondrial functionMyeloid genesNivolumab plus anlotinib hydrochloride in advanced gastric adenocarcinoma and esophageal squamous cell carcinoma: the phase II OASIS trial
Wu J, Zhang S, Yu S, An G, Wang Y, Yu Y, Liang L, Wang Y, Xu X, Xiong Y, Shao D, Shi Z, Li N, Wang J, Jin D, Liu T, Cui Y. Nivolumab plus anlotinib hydrochloride in advanced gastric adenocarcinoma and esophageal squamous cell carcinoma: the phase II OASIS trial. Nature Communications 2024, 15: 8876. PMID: 39406730, PMCID: PMC11480398, DOI: 10.1038/s41467-024-53109-4.Peer-Reviewed Original ResearchConceptsEsophageal squamous cell carcinomaAdvanced gastric adenocarcinomaSquamous cell carcinomaTyrosine kinase inhibitorsGastric adenocarcinomaVariant allele frequencyAnlotinib hydrochlorideCell carcinomaVascular endothelial growth factor inhibitorsAnti-PD-1 antibodySafety of nivolumabAnti-PD-1Disease control rateMedian overall survivalProgression-free survivalGrowth factor inhibitorsPhase II trialOverall response rateOASIS trialPD-1Second-lineOverall survivalImmune signaturesII trialFactor inhibitorsEP.06D.04 Prognostic Value of Variant Allele Frequency in Circulating Tumor DNA for Survival Outcomes in Metastatic Non-Small Cell Lung Cancer
Peleg A, de la Fuente R, Lichtman S, Gomez J, Doroshow D, Hirsch F, Veluswamy R, Marron T, Rohs N, Smith C, Rolfo C. EP.06D.04 Prognostic Value of Variant Allele Frequency in Circulating Tumor DNA for Survival Outcomes in Metastatic Non-Small Cell Lung Cancer. Journal Of Thoracic Oncology 2024, 19: s502-s503. DOI: 10.1016/j.jtho.2024.09.932.Peer-Reviewed Original ResearchP3.06D.04 Role of ctDNA Variant Allele Frequency in Predicting Response to Immune Checkpoint Inhibitors in Non-Small Cell Lung Cancer
de la Fuente R, Peleg A, Litchman S, Gomez J, Doroshow D, Hirsch F, Veluswamy R, Marron T, Smith C, Rohs N, Rolfo C. P3.06D.04 Role of ctDNA Variant Allele Frequency in Predicting Response to Immune Checkpoint Inhibitors in Non-Small Cell Lung Cancer. Journal Of Thoracic Oncology 2024, 19: s323. DOI: 10.1016/j.jtho.2024.09.579.Peer-Reviewed Original ResearchTislelizumab plus cetuximab and irinotecan in refractory microsatellite stable and RAS wild-type metastatic colorectal cancer: a single-arm phase 2 study
Xu X, Ai L, Hu K, Liang L, Lv M, Wang Y, Cui Y, Li W, Li Q, Yu S, Feng Y, Liu Q, Yang Y, Zhang J, Xu F, Yu Y, Liu T. Tislelizumab plus cetuximab and irinotecan in refractory microsatellite stable and RAS wild-type metastatic colorectal cancer: a single-arm phase 2 study. Nature Communications 2024, 15: 7255. PMID: 39179622, PMCID: PMC11343749, DOI: 10.1038/s41467-024-51536-x.Peer-Reviewed Original ResearchConceptsMetastatic colorectal cancerVariant allele frequencyPhase 2 studyEpidermal growth factor receptorAdverse eventsRAS wild-type metastatic colorectal cancerRAS wt metastatic colorectal cancerSingle-arm phase 2 studyWild-type metastatic colorectal cancerColorectal cancerTreatment-related adverse eventsAnti-PD-1Disease control rateProgression-free survivalRAS wild-typeTumor immune responseCombined treatment regimenWild-typeGrowth factor receptorIrinotecan combinationOverall survivalAnti-EGFRPrimary endpointTumor DNASingle-armUltra-sensitive molecular residual disease detection through whole genome sequencing with single-read error correction
Li X, Liu T, Bacchiocchi A, Li M, Cheng W, Wittkop T, Mendez F, Wang Y, Tang P, Yao Q, Bosenberg M, Sznol M, Yan Q, Faham M, Weng L, Halaban R, Jin H, Hu Z. Ultra-sensitive molecular residual disease detection through whole genome sequencing with single-read error correction. EMBO Molecular Medicine 2024, 16: 2188-2209. PMID: 39164471, PMCID: PMC11393307, DOI: 10.1038/s44321-024-00115-0.Peer-Reviewed Original ResearchMolecular residual diseaseCirculating tumor DNAWhole-genome sequencingCell-free DNAGenome sequenceDetection of molecular residual diseaseCirculating tumor DNA detectionResidual disease detectionConsistent with clinical outcomesVariant allele frequencyResidual diseaseMelanoma patientsMonitoring immunotherapyTumor DNAEsophageal cancerClinical outcomesColorectal cancerWGS technologiesAllele frequenciesCancerDNAAnalytical sensitivitySequenceImmunotherapyRelapseCirculating Tumor DNA Dynamics Reveal KRAS G12C Mutation Heterogeneity and Response to Treatment with the KRAS G12C Inhibitor Divarasib in Solid Tumors
Choi Y, Dharia N, Jun T, Chang J, Royer-Joo S, Yau K, Assaf Z, Aimi J, Sivakumar S, Montesion M, Sacher A, LoRusso P, Desai J, Schutzman J, Shi Z, group A. Circulating Tumor DNA Dynamics Reveal KRAS G12C Mutation Heterogeneity and Response to Treatment with the KRAS G12C Inhibitor Divarasib in Solid Tumors. Clinical Cancer Research 2024, 30: of1-of10. PMID: 38995268, PMCID: PMC11369623, DOI: 10.1158/1078-0432.ccr-24-0255.Peer-Reviewed Original ResearchConceptsKRAS G12C mutationTumor fractionSolid tumorsTumor typesG12C mutationOn-treatment time pointsNon-small cell lung cancerMutational heterogeneityAssociated with tumor typeProgression-free survivalPlasma samplesPhase 1 studyCell lung cancerCycle 1 dayAssociated with patient outcomesVariant allele frequencyAssociated with responseCtDNA levelsCtDNA profilingMetastatic sitesTruncal mutationsTumor DNATreatment responseLung cancerTumor tissuesAbstract 971: Validation of a tumor-naïve circulating tumor DNA (ctDNA) response monitoring panel in advanced non-small cell lung cancer (aNSCLC)
Chiang A, Madison R, Huang Y, Fine A, Jin D, Oxnard G, Hughes J, Assaf Z, Cao Y, Antic V, Gjoerup O, Young A, Fabrizio D, Lakhanpal S, Zuniga R, Schulze K, Pasquina L. Abstract 971: Validation of a tumor-naïve circulating tumor DNA (ctDNA) response monitoring panel in advanced non-small cell lung cancer (aNSCLC). Cancer Research 2024, 84: 971-971. DOI: 10.1158/1538-7445.am2024-971.Peer-Reviewed Original ResearchAdvanced non-small cell lung cancerPeripheral blood mononuclear cellsNon-small cell lung cancerRisk of progressionCell lung cancerClonal hematopoiesisTumor fractionGenomic alterationsTumor signalAmerican Association for Cancer Research annual meetingsLung cancerHazard ratioPatient's risk of progressionFrequency of genomic alterationsAssociated with favorable outcomesMolecular responseWeeks of TxProgression free survivalUnivariate Cox proportional hazards regressionCox proportional hazards regressionBlood mononuclear cellsConfidence intervalsVariant allele frequencyCombination of aneuploidyProportional hazards regressionPrecision needle-punch tumor enrichment from paraffin blocks improves the detection of clinically actionable genomic alterations and biomarkers
Lin D, Huang R, Ladas I, Keller R, Patel N, Lakis S, Decker B, Janovitz T, Mata D, Ross J, Vergilio J, Elvin J, Herbst R, Mack P, Killian J. Precision needle-punch tumor enrichment from paraffin blocks improves the detection of clinically actionable genomic alterations and biomarkers. Frontiers In Oncology 2024, 14: 1328512. PMID: 38444675, PMCID: PMC10912171, DOI: 10.3389/fonc.2024.1328512.Peer-Reviewed Original ResearchTumor mutational burdenTumor purityTumor specimensNext-generation sequencingClinically actionable genomic alterationsMicrosatellite instabilityBiomarker statusTissue-conserving methodTissue blocksHigh tumor purityLow tumor purityComplex biomarkersSurgical pathology materialClinical samplesClinical trial enrollmentVariant allele frequencyResidual tumorMutational burdenTumor enrichmentTumor contentTumor cellsGenomic alterationsFormalin-fixedParaffin blocksDetect mutations
2023
Divarasib plus cetuximab in KRAS G12C-positive colorectal cancer: a phase 1b trial
Desai J, Alonso G, Kim S, Cervantes A, Karasic T, Medina L, Shacham-Shmueli E, Cosman R, Falcon A, Gort E, Guren T, Massarelli E, Miller W, Paz-Ares L, Prenen H, Amatu A, Cremolini C, Kim T, Moreno V, Ou S, Passardi A, Sacher A, Santoro A, Stec R, Ulahannan S, Arbour K, Lorusso P, Luo J, Patel M, Choi Y, Shi Z, Mandlekar S, Lin M, Royer-Joo S, Chang J, Jun T, Dharia N, Schutzman J, Han S. Divarasib plus cetuximab in KRAS G12C-positive colorectal cancer: a phase 1b trial. Nature Medicine 2023, 30: 271-278. PMID: 38052910, PMCID: PMC10803265, DOI: 10.1038/s41591-023-02696-8.Peer-Reviewed Original ResearchPhase 1b trialColorectal cancerSafety profileMedian progression-free survivalTreatment-related adverse eventsInhibitor-naive patientsKRAS G12C inhibitionAntitumor activityManageable safety profileObjective response rateProgression-free survivalPreliminary antitumor activityKRAS G12C mutationKRAS G12C inhibitorsEpidermal growth factor receptorVariant allele frequencyGrowth factor receptorAdverse eventsMedian durationTreatment withdrawalPoor prognosisDisease progressionArm CDose reductionG12C inhibitorsAbstract A123: Circulating tumor DNA (ctDNA) genomic and epigenomic profiling (GuardantINFINITY) for diagnosis of DNA damage repair (DDR) loss of function (LOF) and response monitoring in the TRESR and ATTACC trials
Rosen E, Schonhoft J, Silverman I, Yablonovitch A, Sethuraman S, Nejad P, Ulanet D, Yang J, Kim I, Fei K, Xu Y, Lagow E, Zhang S, Cai M, Koehler M, Carneiro B, Lheureux S, Cecchini M, Herzberg B, Reis-Filho J, Rimkunas V, Yap T. Abstract A123: Circulating tumor DNA (ctDNA) genomic and epigenomic profiling (GuardantINFINITY) for diagnosis of DNA damage repair (DDR) loss of function (LOF) and response monitoring in the TRESR and ATTACC trials. Molecular Cancer Therapeutics 2023, 22: a123-a123. DOI: 10.1158/1535-7163.targ-23-a123.Peer-Reviewed Original ResearchCirculating tumor DNAVariant allele frequencyDNA damage repairEpigenomic profilingTumor DNADamage repairResponse monitoringCirculating tumor DNA sequencingLow variant allele frequencyTreated with PARPiPhase 1 studyCell-free DNAMolecular responseIntragenic deletionsEpigenetic analysisAllele frequenciesRad3-relatedCH variantsGenomic alterationsOn-treatmentClinical outcomesPancreatic cancerAtaxia telangiectasiaPathogenic alterationsEvaluable ptsDurable Continuous Transfusion Independence (TI) with Imetelstat in IMerge Phase 3 for Patients with Heavily Transfused Non-Del(5q) Lower-Risk Myelodysplastic Syndromes (LR-MDS) Relapsed/Refractory (R/R) to or Ineligible for Erythropoiesis-Stimulating Agents (ESAs)
Platzbecker U, Komrokji R, Zeidan A, Fenaux P, Sekeres M, Savona M, Madanat Y, Jonášová A, Illmer T, Sherman L, Berry T, Riggs J, Xia Q, Navada S, Wan Y, Huang F, Feller F, Santini V. Durable Continuous Transfusion Independence (TI) with Imetelstat in IMerge Phase 3 for Patients with Heavily Transfused Non-Del(5q) Lower-Risk Myelodysplastic Syndromes (LR-MDS) Relapsed/Refractory (R/R) to or Ineligible for Erythropoiesis-Stimulating Agents (ESAs). Blood 2023, 142: 4605. DOI: 10.1182/blood-2023-181154.Peer-Reviewed Original ResearchLower-risk myelodysplastic syndromesErythropoiesis stimulating agentsPhase 3 trialTransfusion independenceVariant allele frequencyEnd pointTransfusion burdenAdverse eventsRed blood cell transfusionExploratory end pointsFrequent adverse eventsPrimary end pointRBC transfusion burdenReversible grade 3Secondary end pointsBlood cell transfusionDisease-modifying activityKaplan-Meier methodDuration of responseLoss of responseAdditional baseline characteristicsHigh telomerase activityCell transfusionBaseline characteristicsClinical responseTP53 Y220C Mutations in Patients with Myeloid Malignancies
Gener-Ricos G, Bewersdorf J, Loghavi S, Goldberg A, Famulare C, Issa G, Borthakur G, Kadia T, Carter B, Patel K, Andreeff M, Stein E, DiNardo C. TP53 Y220C Mutations in Patients with Myeloid Malignancies. Blood 2023, 142: 1477. DOI: 10.1182/blood-2023-189343.Peer-Reviewed Original ResearchLeukemia-free survivalAcute myeloid leukemiaMedian leukemia-free survivalVariant allele frequencyMedian follow-upStem cell transplantationMyeloid neoplasmsHot spot mutationsTP53 mutationsCo-mutationsFollow-upMyelodysplastic syndromeMyeloid malignanciesOverall survivalHematologic malignanciesMyeloid leukemiaSolid tumorsTransformation to acute myeloid leukemiaMedian variant allele frequencyTherapy-related myeloid neoplasmsAcute myeloid leukemia transformationMemorial Sloan-Kettering Cancer CenterY220C mutationTP53 co-mutationsNext generation sequencing assayMutations in the RNA Splicing Factors U2AF1 and SRSF2 are Context-Dependent in Myeloproliferative Neoplasms
Bale S, Kim C, How J, Wazir M, Weeks L, Stahl M, Luskin M, DeAngelo D, Lindsley C, Kim A, Mullally A, Marneth A. Mutations in the RNA Splicing Factors U2AF1 and SRSF2 are Context-Dependent in Myeloproliferative Neoplasms. Blood 2023, 142: 1788. DOI: 10.1182/blood-2023-178657.Peer-Reviewed Original ResearchVariant allele frequencySRSF2 mutationsCALR mutationsMyeloproliferative neoplasmsU2AF1 mutationsPathogenic mutationsSplicing factor mutationsCo-mutationsGene mutationsMPN phenotypic driver mutationsPolymerase chain reactionDriver mutationsMyeloproliferative neoplasm driver mutationsSplicing factor genes mutationsCD34-positive bone marrow cellsPositive bone marrow cellsPhenotypic driver mutationsSpliceosome gene mutationsNegative myeloproliferative neoplasmsComprehensive molecular profilingMyeloproliferative neoplasm patientsHematopoietic growth factorsBone marrow cellsSplicing factor U2AF1Pathogenic mutation(sSingle-Agent Divarasib (GDC-6036) in Solid Tumors with a KRAS G12C Mutation
Sacher A, LoRusso P, Patel M, Miller W, Garralda E, Forster M, Santoro A, Falcon A, Kim T, Paz-Ares L, Bowyer S, de Miguel M, Han S, Krebs M, Lee J, Cheng M, Arbour K, Massarelli E, Choi Y, Shi Z, Mandlekar S, Lin M, Royer-Joo S, Chang J, Dharia N, Schutzman J, Desai J. Single-Agent Divarasib (GDC-6036) in Solid Tumors with a KRAS G12C Mutation. New England Journal Of Medicine 2023, 389: 710-721. PMID: 37611121, DOI: 10.1056/nejmoa2303810.Peer-Reviewed Original ResearchConceptsMedian progression-free survivalTreatment-related adverse eventsProgression-free survivalAdverse eventsSolid tumorsG12C mutationLow-grade adverse eventsGrade 3 eventsGrade 4 eventsTreatment-related deathsDiscontinuation of treatmentMetastatic solid tumorsPhase 1 studyDurable clinical responsesBiomarkers of responseKRAS G12C mutationAssessment of safetyVariant allele frequencyClinical responseColorectal cancerSerial assessmentDose reductionG12C inhibitorsPatientsTumor DNA
2022
TP53-altered higher-risk myelodysplastic syndromes/neoplasms and acute myeloid leukemia: a distinct genetic entity with unique unmet needs
Ball S, Loghavi S, Zeidan A. TP53-altered higher-risk myelodysplastic syndromes/neoplasms and acute myeloid leukemia: a distinct genetic entity with unique unmet needs. Leukemia & Lymphoma 2022, 64: 540-550. PMID: 36323304, DOI: 10.1080/10428194.2022.2136969.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsAcute myeloid leukemiaMyelodysplastic syndromeVariant allele frequencyMyeloid leukemiaMDS/acute myeloid leukemiaIndependent poor prognostic factorBCL2 inhibitor venetoclaxPoor prognostic factorDisease-modifying therapiesIntensive chemotherapyBlast countClinical coursePrognostic factorsInvestigational agentsDisease entityClinical studiesInhibitor venetoclaxMyeloid neoplasmsResponse ratePathogenic alterationsNeoplasmsDistinct genetic entitiesLeukemiaGenetic characteristicsAllele frequenciesAbstract A040: Intra-epithelia cell dynamics shape evolutionary dynamics and selection of therapy resistant clones in lung cancer
Fu X, Bhargava A, Bailey S, Biswas D, Ruiz C, Kumar S, French P, McGranahan N, Swanton C, Bates P, Sahai E. Abstract A040: Intra-epithelia cell dynamics shape evolutionary dynamics and selection of therapy resistant clones in lung cancer. Cancer Research 2022, 82: a040-a040. DOI: 10.1158/1538-7445.evodyn22-a040.Peer-Reviewed Original ResearchEvolutionary dynamicsResistant clonesEnhanced cell motilityCapability of cancer cellsCell-cell cohesionRNA sequencing dataCell dynamicsExpansion of clonesModel of cell proliferationLung cancer cell linesVariant allele frequencySequence dataNeutral evolutionCell motilityGenomic complexityCancer cell linesCell line modelsAllele frequenciesSelection pressureRandom motilityGrowth arrestMutational processesClonesCell migrationIntra-tumor heterogeneity
2021
Immune and Epigenetic Landscape of TP53-mutated Acute Myeloid Leukemia (AML) and Higher-Risk Myelodysplastic Syndromes (HR-MDS)
Zeidan A, Bewersdorf J, Hasle V, Thompson E, de Menezes D, Rose S, Boss I, Fox B. Immune and Epigenetic Landscape of TP53-mutated Acute Myeloid Leukemia (AML) and Higher-Risk Myelodysplastic Syndromes (HR-MDS). Blood 2021, 138: 3371. DOI: 10.1182/blood-2021-146329.Peer-Reviewed Original ResearchHigh-risk myelodysplastic syndromeClinical Trials CommitteeAcute myeloid leukemiaBristol-Myers SquibbCurrent equity holderPoor-risk cytogeneticsVariant allele frequencyAML ptsOverall response rateTrials CommitteeMedian OSTP53 mutationsMyeloid neoplasmsFlow cytometryPeripheral bloodT cell genesHigh expressionBone marrowAverage variant allele frequencyRandomized phase 2 studyBone marrow flow cytometryT-cell gene signatureTumor cellsBM blast percentageIPSS-R scoreMulticenter Analysis of Treatment and Outcomes for Patient with TP53 Mutated AML in the Era of Novel Therapies; Significant Impact of Allogeneic Stem Cell Transplantation on Survival
Badar T, Litzow M, Shallis R, Bewersdorf J, Saliba A, De Camargo Correia G, Stahl M, Goldberg A, Atallah E, Foran J. Multicenter Analysis of Treatment and Outcomes for Patient with TP53 Mutated AML in the Era of Novel Therapies; Significant Impact of Allogeneic Stem Cell Transplantation on Survival. Blood 2021, 138: 797. DOI: 10.1182/blood-2021-147639.Peer-Reviewed Original ResearchCR/CRiProportion of patientsStem cell transplantationComplex cytogeneticsVariant allele frequencyCPX-351Overall survivalAML patientsNovel therapiesTP53 mutationsCell transplantationUnivariate analysisAllogeneic hematopoietic stem cell transplantationMedian progression-free survivalAllogeneic stem cell transplantationHematopoietic stem cell transplantationAdvisory CommitteeAML induction therapyExtra-medullary diseaseHigh-risk AMLInduction/consolidationVenetoclax combination therapyVenetoclax-based regimensMedian overall survivalMulticenter observational study
This site is protected by hCaptcha and its Privacy Policy and Terms of Service apply