2021
Oral Decitabine/Cedazuridine in Patients with Lower Risk Myelodysplastic Syndrome: A Longer-Term Follow-up of from the Ascertain Study
Garcia-Manero G, McCloskey J, Griffiths E, Yee K, Zeidan A, Al-Kali A, Deeg H, Patel P, Sabloff M, Keating M, Dao K, Zhu N, Gabrail N, Fazal S, Maly J, Odenike O, Kantarjian H, DeZern A, O'Connell C, Roboz G, Busque L, Wells R, Amin H, Randhawa J, Leber B, Hao Y, Keer H, Azab M, Savona M. Oral Decitabine/Cedazuridine in Patients with Lower Risk Myelodysplastic Syndrome: A Longer-Term Follow-up of from the Ascertain Study. Blood 2021, 138: 66. PMCID: PMC8701611, DOI: 10.1182/blood-2021-144648.Peer-Reviewed Original ResearchLower-risk myelodysplastic syndromesClinical Trials CommitteeMedian leukemia-free survivalMedian overall survivalRisk myelodysplastic syndromesBristol-Myers SquibbMyelodysplastic syndromeTransfusion independenceTrials CommitteeOral DECDNA methyltransferase inhibitorOverall survivalComplete responseAstex PharmaceuticalsSpeakers bureauCC-486Hematologic improvementDaiichi SankyoTreatment-emergent adverse eventsHigh-risk MDS patientsAllogeneic stem cell transplantSARS-CoV-2 infectionAdvisory CommitteeRandomized cross-over studyPandemic SARS-CoV-2 infectionSabatolimab (MBG453) Combination Treatment Regimens for Patients (Pts) with Higher-Risk Myelodysplastic Syndromes (HR-MDS): The MDS Studies in the Stimulus Immuno-Myeloid Clinical Trial Program
Zeidan A, Al-Kali A, Borate U, Cluzeau T, DeZern A, Esteve J, Giagounidis A, Kobata K, Lyons R, Platzbecker U, Sallman D, Santini V, Sanz G, Sekeres M, Wei A, Xiao Z, Van Hoef M, Nourry-Boulot C, Sadek I, Bengoudifa B, Sachs C, Sabo J, Garcia-Manero G. Sabatolimab (MBG453) Combination Treatment Regimens for Patients (Pts) with Higher-Risk Myelodysplastic Syndromes (HR-MDS): The MDS Studies in the Stimulus Immuno-Myeloid Clinical Trial Program. Blood 2021, 138: 4669. DOI: 10.1182/blood-2021-145626.Peer-Reviewed Original ResearchHigh-risk myelodysplastic syndromeClinical Trials CommitteeProgression-free survivalHematopoietic stem cell transplantLeukemia-free survivalClinical trial programLeukemic stem cellsComplete responsePrimary endpointOverall survivalTim-3Trials CommitteeHMA therapySecondary endpointsII trialAdverse eventsNovartis Pharma AGCombination therapyMyeloid malignanciesTrial programSpeakers bureauBristol-Myers SquibbIntensive chemotherapyPartial remissionTarget enrollmentImmune 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 scoreOutcomes for Patients with Late-Stage Mutant-IDH2 (m IDH2) Relapsed/Refractory Acute Myeloid Leukemia (R/R AML) Treated with Enasidenib Vs Other Lower-Intensity Therapies in the Randomized, Phase 3 IDHentify Trial
DiNardo C, Montesinos P, Schuh A, Papayannidis C, Vyas P, Wei A, Zeidan A, Bluemmert I, Yu X, Hasan M, Martin-Regueira P, de Botton S. Outcomes for Patients with Late-Stage Mutant-IDH2 (m IDH2) Relapsed/Refractory Acute Myeloid Leukemia (R/R AML) Treated with Enasidenib Vs Other Lower-Intensity Therapies in the Randomized, Phase 3 IDHentify Trial. Blood 2021, 138: 1243. DOI: 10.1182/blood-2021-147593.Peer-Reviewed Original ResearchClinical Trials CommitteeBest supportive careEvent-free survivalBristol-Myers SquibbIntermediate-dose cytarabineMedian overall survivalR AMLOverall survivalHematologic improvementTransfusion independenceTrials CommitteeCurrent equity holderSpeakers bureauDaiichi SankyoRefractory acute myeloid leukemiaAdvisory CommitteeAdverse-risk AMLConventional care regimensLow-dose cytarabineMedian age overallPrimary refractory AMLStudy drug doseOpen-label trialLow-intensity therapyOverall response rateHealth-Related Quality of Life (HRQoL) during Treatment with Enasidenib (ENA) Plus Azacitidine (AZA) in Patients with Newly Diagnosed Mutant IDH2 (m IDH2) Acute Myeloid Leukemia (AML) Not Eligible for Intensive Chemotherapy (IC)
DiNardo C, Dohner H, Zeidan A, Schuh A, Vyas P, Stein E, Wei A, de Botton S, Chen C, Lord-Bessen J, Martin-Regueira P, Lersch F, Gong J, Guo S, Shi L, Montesinos P. Health-Related Quality of Life (HRQoL) during Treatment with Enasidenib (ENA) Plus Azacitidine (AZA) in Patients with Newly Diagnosed Mutant IDH2 (m IDH2) Acute Myeloid Leukemia (AML) Not Eligible for Intensive Chemotherapy (IC). Blood 2021, 138: 1244. DOI: 10.1182/blood-2021-147601.Peer-Reviewed Original ResearchClinical Trials CommitteeAcute myeloid leukemiaEQ-5D VASQLQ-C30 domainsCurrent equity holderBristol-Myers SquibbGHS/QoLGlobal health statusOverall response rateTrials CommitteeQLQ-C30 scoresEQ-5DIntensive chemotherapyPhysical functioningRole functioningDaiichi SankyoSpeakers bureauEvaluable ptsBristol-Myers Squibb CompanyHRQoL scoresDyspnea domainEQ-5D visual analog scale scoresJazz PharmaceuticalsMeaningful improvementsVisual analog scale scoreVenetoclax Plus Azacitidine (VEN-AZA) Vs. Intensive Chemotherapy (IC) As Induction for Patients with Acute Myeloid Leukemia (AML): Retrospective Analysis of an Electronic Medical Records (EMR) Database in the United States
Zeidan A, Pollyea D, Borate U, Vasconcelos A, Potluri R, Rotter D, Kiendrebeogo Z, Gaugler L, Bonifacio G, Chen C. Venetoclax Plus Azacitidine (VEN-AZA) Vs. Intensive Chemotherapy (IC) As Induction for Patients with Acute Myeloid Leukemia (AML): Retrospective Analysis of an Electronic Medical Records (EMR) Database in the United States. Blood 2021, 138: 277. DOI: 10.1182/blood-2021-147926.Peer-Reviewed Original ResearchClinical Trials CommitteeRelapse-free survivalAcute myeloid leukemiaMedian relapse-free survivalCurrent equity holderElectronic medical record databaseBristol-Myers SquibbSubgroups of ptsIntensive chemotherapyIC cohortStart of therapyOverall survivalTrials CommitteeMedical record databaseRemission rateCR rateAge-based subgroupsYears subgroupRecord databaseIncomplete hematologic recovery (CRi) ratesReal-world clinical practicePhase 3 trial dataAdvisory CommitteeDaiichi SankyoGood remission rateCharacteristics and Clinical Outcome of Patients with Clonal Cytopenias of Undetermined Significance: A Large Retrospective Multi-Center International Study
Xie Z, Hyun M, Komrokji R, Zeidan A, Madanat Y, Zeidner J, Coombs C, Griffiths E, Lai C, Kishtagari A, Foran J, Badar T, Yi C, Desai P, Ades L, Osman A, Taylor J, Deeg H, Brunner A, Carraway H, Ali N, Bewersdorf J, Prebet T, Singh A, Tsai C, Chandhok N, Soong D, Patnaik M, Savona M, Al-Kali A. Characteristics and Clinical Outcome of Patients with Clonal Cytopenias of Undetermined Significance: A Large Retrospective Multi-Center International Study. Blood 2021, 138: 2158. DOI: 10.1182/blood-2021-146254.Peer-Reviewed Original ResearchClinical Trials CommitteeProgression-free survivalIndependent review committeeOverall survivalTrials CommitteeDisease progressionBristol-Myers SquibbMyeloid neoplasmsResponse rateFunctional pathway analysisSpeakers bureauUndetermined significanceMultivariable modelClonal cytopeniaReview CommitteeMedian progression-free survivalBoehringer IngelheimAdvisory CommitteeMulti-centre international studyCG abnormalitiesCox proportional hazards modelGene panelDaiichi SankyoBaseline clinical dataKaplan-Meier methodEnasidenib plus azacitidine versus azacitidine alone in patients with newly diagnosed, mutant-IDH2 acute myeloid leukaemia (AG221-AML-005): a single-arm, phase 1b and randomised, phase 2 trial
DiNardo CD, Schuh AC, Stein EM, Montesinos P, Wei AH, de Botton S, Zeidan AM, Fathi AT, Kantarjian HM, Bennett JM, Frattini MG, Martin-Regueira P, Lersch F, Gong J, Hasan M, Vyas P, Döhner H. Enasidenib plus azacitidine versus azacitidine alone in patients with newly diagnosed, mutant-IDH2 acute myeloid leukaemia (AG221-AML-005): a single-arm, phase 1b and randomised, phase 2 trial. The Lancet Oncology 2021, 22: 1597-1608. PMID: 34672961, DOI: 10.1016/s1470-2045(21)00494-0.Peer-Reviewed Original ResearchMeSH KeywordsAgedAminopyridinesAntimetabolites, AntineoplasticAntineoplastic Combined Chemotherapy ProtocolsAzacitidineDrug Administration ScheduleDrug-Related Side Effects and Adverse ReactionsFemaleHumansIsocitrate DehydrogenaseLeukemia, Myeloid, AcuteMaleMutationProgression-Free SurvivalRandom AllocationTreatment OutcomeTriazinesConceptsAcute myeloid leukemiaSerious treatment-related adverse eventsTreatment-related adverse eventsDose-finding portionOverall response rateMyeloid leukemiaAdverse eventsFebrile neutropeniaCombination groupInterim analysisEastern Cooperative Oncology Group performance statusCommon treatment-related grade 3Response rateInteractive web response systemTreatment-related grade 3Phase 1b/2 trialPrespecified interim analysisTreatment-related deathsPhase 2 trialWeb response systemPhase 2Acute myeloid leukemia subtypesPhase 2 portionBristol-Myers SquibbAzacitidine monotherapy
2020
Molecular Characterization of Clinical Response and Relapse in Patients with IDH1-Mutant Newly Diagnosed Acute Myeloid Leukemia Treated with Ivosidenib and Azacitidine
Daigle S, Choe S, DiNardo C, Stein A, Stein E, Fathi A, Frankfurt O, Schuh A, Döhner H, Martinelli G, Patel P, Raffoux E, Tan P, Zeidan A, De Botton S, Stone R, Frattini M, Franovic A, Xu E, Winkler T, Wu B, Vyas P. Molecular Characterization of Clinical Response and Relapse in Patients with IDH1-Mutant Newly Diagnosed Acute Myeloid Leukemia Treated with Ivosidenib and Azacitidine. Blood 2020, 136: 49-51. DOI: 10.1182/blood-2020-136922.Peer-Reviewed Original ResearchPeripheral blood mononuclear cellsAcute myeloid leukemiaBone marrow mononuclear cellsCurrent equity holderIntensive induction chemotherapyAgios PharmaceuticalsSafety monitoring boardIsocitrate dehydrogenase 1Daiichi SankyoSeattle GeneticsSpeakers bureauBristol-Myers SquibbIDH2 mutationsPTC TherapeuticsClinical responseMononuclear cellsClinical trialsDisease progressionMyeloid leukemiaMonitoring boardRefractory (R/R) AMLMutant IDH1R AMLAdvisory CommitteeForty-sevenGilteritinib Remains Clinically Active in Relapsed/Refractory FLT3 Mutated AML Previously Treated with FLT3 inhibitors
Numan Y, Rahman Z, Grenet J, Boisclair S, Bewersdorf J, Barth D, Zeidan A, Yilmaz M, Dinner S, Deutsch Y, Frankfurt O, Litzow M, Al-Kali A, Foran J, Sproat L, Jovanovic B, Daver N, Perl A, Altman J. Gilteritinib Remains Clinically Active in Relapsed/Refractory FLT3 Mutated AML Previously Treated with FLT3 inhibitors. Blood 2020, 136: 5-7. DOI: 10.1182/blood-2020-137251.Peer-Reviewed Original ResearchStem cell transplantMedian survivalFLT3 mutationsBristol-Myers SquibbDaiichi SankyoBoehringer IngelheimCRC ratesLymphoma SocietyCombination therapyPolymerase chain reactionFLT3-ITDSingle agentDrug resistanceAdvisory CommitteeBone marrow flow cytometryComposite complete remissionFLT3-D835 mutationsHigher CRCS ratesNon-transplanted patientsPoor median survivalKaplan-Meier curvesMulti-institutional analysisLog-rank testBayer HealthCare PharmaceuticalsMAPK pathwayBlast MRD CML 1 Trial: Blockade of PD-1 Added to Standard Therapy to Target Measurable Residual Disease (MRD) in Chronic Myeloid Leukemia (CML)- a Phase II Study of Adding the Anti-PD-1 Pembrolizumab to Tyrosine Kinase Inhibitors in Patients with Chronic Myeloid Leukemia and Persistently Detectable Minimal Residual Disease: A Trial of the ECOG-ACRIN Cancer Research Group (EA9171)
Zeidan A, Wang V, Radich J, Bewersdorf J, Bhatt V, Sharon E, Gore S, Luger S, Litzow M. Blast MRD CML 1 Trial: Blockade of PD-1 Added to Standard Therapy to Target Measurable Residual Disease (MRD) in Chronic Myeloid Leukemia (CML)- a Phase II Study of Adding the Anti-PD-1 Pembrolizumab to Tyrosine Kinase Inhibitors in Patients with Chronic Myeloid Leukemia and Persistently Detectable Minimal Residual Disease: A Trial of the ECOG-ACRIN Cancer Research Group (EA9171). Blood 2020, 136: 1. DOI: 10.1182/blood-2020-137734.Peer-Reviewed Original ResearchUndetectable minimal residual diseaseChronic myeloid leukemiaMeasurable residual diseaseTyrosine kinase inhibitorsTKI discontinuationTKI therapyMinimal residual diseaseCML patientsResidual diseaseMyeloid leukemiaBristol-Myers SquibbPembrolizumab therapyAdverse eventsPD-1T cellsCML cellsAnti-PD-1/PD-L1 therapyBlast phase chronic myeloid leukemiaPilot phase II clinical trialThird-line tyrosine kinase inhibitorsAllogeneic hematopoietic stem cell transplantAnti-PD-1 monoclonal antibodyPD-1/PD-L1Anti-PD-1 pembrolizumabDetectable minimal residual disease
2019
Safety, Efficacy and Biomarker Analysis of a Phase 1b/2 Study of Onvansertib (ONV), a Polo-like Kinase 1 (PLK1) Inhibitor, in Combination with Low-Dose Cytarabine (LDAC) or Decitabine (DEC) in Patients (pts) with Relapsed/Refractory Acute Myeloid Leukemia (R/R AML)
Zeidan A, Schiller G, Lin T, Becker P, Patel P, Wang E, Spira A, Tsai M, Ridinger M, Croucher P, Erlander M, Silberman S. Safety, Efficacy and Biomarker Analysis of a Phase 1b/2 Study of Onvansertib (ONV), a Polo-like Kinase 1 (PLK1) Inhibitor, in Combination with Low-Dose Cytarabine (LDAC) or Decitabine (DEC) in Patients (pts) with Relapsed/Refractory Acute Myeloid Leukemia (R/R AML). Blood 2019, 134: 230. DOI: 10.1182/blood-2019-126262.Peer-Reviewed Original ResearchPositive ptsBiomarker positivityPhase 1bBristol-Myers SquibbSpeakers bureauObjective responseCount recoveryPreliminary efficacyBlood samplesNegative groupRelapsed/Refractory Acute Myeloid LeukemiaADC therapeuticsDay 1Jazz PharmaceuticalsRefractory acute myeloid leukemiaBoehringer IngelheimDaiichi SankyoIncomplete count recoveryPhase 1b/2 studyPreclinical AML modelsSubset of ptsLow-dose cytarabinePredictive gene expression signaturesDose-escalation trialPlatelet count recovery