2023
Validation of the Composite Complete Response (cCR) Definitions in the International Working Group (IWG) 2023 Criteria in Patients (Pts) with Higher-Risk Myelodysplastic Syndromes/Neoplasms (HR-MDS) Treated with Hypomethylating Agents (HMA) - a Large, Multicenter, Retrospective Analysis from the Validate Database
Bewersdorf J, Kewan T, Blaha O, Stahl M, Al Ali N, DeZern A, Sekeres M, Uy G, Carraway H, Desai P, Griffiths E, Stein E, Brunner A, McMahon C, Zeidner J, Savona M, Stempel J, Chandhok N, Logothetis C, Roboz G, Rolles B, Wang E, Harris A, Amaya M, Hawkins H, Grenet J, Shallis R, Xie Z, Maciejewski J, Sallman D, Della Porta M, Komrokji R, Zeidan A. Validation of the Composite Complete Response (cCR) Definitions in the International Working Group (IWG) 2023 Criteria in Patients (Pts) with Higher-Risk Myelodysplastic Syndromes/Neoplasms (HR-MDS) Treated with Hypomethylating Agents (HMA) - a Large, Multicenter, Retrospective Analysis from the Validate Database. Blood 2023, 142: 324. DOI: 10.1182/blood-2023-180299.Peer-Reviewed Original ResearchImproved OSHypomethylating agentHMA initiationMedian OSResponse assessmentTP53 mutationsResponse definitionsPartial hematologic recoveryPredictors of OSMultivariable Cox modelBone marrow blastsKaplan-Meier analysisLog-rank testOverall response rateEfficacy of therapyMultivariable regression modelsReal-world analysisAllo-HCTBM assessmentBM evaluationHemoglobin thresholdHematologic recoveryMarrow blastsMedian durationMedian age
2022
Evaluating complete remission with partial hematologic recovery (CRh) as a response criterion in myelodysplastic syndromes (MDS)
Brunner A, Gavralidis A, Ali N, Hunter A, Komrokji R, Zeidan A, Sallman D. Evaluating complete remission with partial hematologic recovery (CRh) as a response criterion in myelodysplastic syndromes (MDS). Blood Cancer Journal 2022, 12: 153. PMID: 36379923, PMCID: PMC9666661, DOI: 10.1038/s41408-022-00748-9.Peer-Reviewed Original ResearchConceptsPartial hematologic recoveryMyelodysplastic syndromeHematologic recoveryResponse criteriaCR/CRhIWG 2006 criteriaDuration of therapyBest overall responseTime of therapyCR responseCRH responseDNMTi therapyOS associationComplete remissionMedian OSOverall survivalAdult patientsAllogeneic transplantsMedian ageMDS patientsMultivariable analysisClinical trialsSimilar survivalPatientsTherapyAML-055 Outcomes Based on Sequential Use of Venetoclax Based Therapy and Targeted Therapy in Acute Myeloid Leukemia (AML)
Stahl M, Shallis R, Derkach A, Goldberg A, Stein A, Stein E, Marcucci G, Zeidan A, Shimony S, DeAngelo D, Stone R, Aldoss I, Ball B, Bewersdorf J. AML-055 Outcomes Based on Sequential Use of Venetoclax Based Therapy and Targeted Therapy in Acute Myeloid Leukemia (AML). Clinical Lymphoma Myeloma & Leukemia 2022, 22: s209-s210. DOI: 10.1016/s2152-2650(22)01214-9.Peer-Reviewed Original ResearchOverall response rateAcute myeloid leukemiaMorphologic leukemia-free stateOverall survivalComplete responseIDH2 inhibitorsMedian OSPartial remissionTargeted therapyEffective salvage therapyIncomplete count recoveryMedian overall survivalShorter median OSRetrospective cohort studyShorter overall survivalAcademic cancer centerFLT3-ITD mutationAlternative therapeutic strategiesSalvage therapyCohort studyCount recoveryInhibitor therapyTargeted agentsClinical efficacyCancer CenterEfficacy of FLT3 and IDH1/2 inhibitors in patients with acute myeloid leukemia previously treated with venetoclax
Bewersdorf JP, Shallis RM, Derkach A, Goldberg AD, Stein A, Stein EM, Marcucci G, Zeidan AM, Shimony S, DeAngelo DJ, Stone RM, Aldoss I, Ball BJ, Stahl M. Efficacy of FLT3 and IDH1/2 inhibitors in patients with acute myeloid leukemia previously treated with venetoclax. Leukemia Research 2022, 122: 106942. PMID: 36108424, DOI: 10.1016/j.leukres.2022.106942.Peer-Reviewed Original ResearchConceptsAcute myeloid leukemiaIDH2 inhibitorsMyeloid leukemiaResponse rateRetrospective cohort studyOverall response rateRAS pathway mutationsNovel therapeutic strategiesMedian OSR AMLCohort studyShorter OSLandmark trialsTargeted agentsFrontline treatmentMutant FLT3Combination therapyTreatment optionsIDH1/2 inhibitorsDisease progressionTherapeutic strategiesPatientsSmall molecule inhibitorsVenetoclaxTherapy
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 score
2020
Effect of enasidenib (ENA) plus azacitidine (AZA) on complete remission and overall response versus AZA monotherapy in mutant -IDH2 ( mIDH2 ) newly diagnosed acute myeloid leukemia (ND-AML).
Dinardo C, Schuh A, Stein E, Montesinos P, Wei A, De Botton S, Zeidan A, Fathi A, Quek L, Kantarjian H, Frattini M, Lersch F, Gong J, Franovic A, Vyas P, Dohner H. Effect of enasidenib (ENA) plus azacitidine (AZA) on complete remission and overall response versus AZA monotherapy in mutant -IDH2 ( mIDH2 ) newly diagnosed acute myeloid leukemia (ND-AML). Journal Of Clinical Oncology 2020, 38: 7501-7501. DOI: 10.1200/jco.2020.38.15_suppl.7501.Peer-Reviewed Original ResearchOverall response rateDuration of responseGrade 3Randomized phase I/II studyPhase I/II studyResponse rateIDH differentiation syndromePoor-risk cytogeneticsComplete remission rateIntermediate-risk cytogeneticsEvent-free survivalPhase II portionImproved response ratesAcute myeloid leukemiaMost common reasonsMutant IDH2AZA monotherapyDifferentiation syndromeECOG PSFebrile neutropeniaIntensive chemotherapyMedian EFSMedian OSPt ageComplete remission
2019
Hypomethylating agent (HMA) therapy use and survival in older adults with Refractory Anemia with Excess Blasts (RAEB) in the United States (USA): a large propensity score-matched population-based study†
Davidoff AJ, Hu X, Bewersdorf JP, Wang R, Podoltsev NA, Huntington SF, Gore SD, Ma X, Zeidan AM. Hypomethylating agent (HMA) therapy use and survival in older adults with Refractory Anemia with Excess Blasts (RAEB) in the United States (USA): a large propensity score-matched population-based study†. Leukemia & Lymphoma 2019, 61: 1178-1187. PMID: 31878809, PMCID: PMC7735409, DOI: 10.1080/10428194.2019.1703970.Peer-Reviewed Original ResearchConceptsHigh-risk myelodysplastic syndromeExcess blastsRefractory anemiaOverall survival benefitRetrospective cohort studyMedian OSOS benefitRAEB patientsCohort studySurvival benefitTherapy useMyelodysplastic syndromeClinical trialsLower riskMedicare dataPatientsPropensity scoreOlder adultsDiagnosisAnemiaQuartileUnited StatesAssociationEnd resultOSEfficacy and Safety of Azacitidine (AZA) in Combination with the Anti-PD-L1 Durvalumab (durva) for the Front-Line Treatment of Older Patients (pts) with Acute Myeloid Leukemia (AML) Who Are Unfit for Intensive Chemotherapy (IC) and Pts with Higher-Risk Myelodysplastic Syndromes (HR-MDS): Results from a Large, International, Randomized Phase 2 Study
Zeidan A, Cavenagh J, Voso M, Taussig D, Tormo M, Boss I, Copeland W, Gray V, Previtali A, O'Connor T, Rose S, Beach C, Silverman L. Efficacy and Safety of Azacitidine (AZA) in Combination with the Anti-PD-L1 Durvalumab (durva) for the Front-Line Treatment of Older Patients (pts) with Acute Myeloid Leukemia (AML) Who Are Unfit for Intensive Chemotherapy (IC) and Pts with Higher-Risk Myelodysplastic Syndromes (HR-MDS): Results from a Large, International, Randomized Phase 2 Study. Blood 2019, 134: 829. DOI: 10.1182/blood-2019-122896.Peer-Reviewed Original ResearchHigh-risk myelodysplastic syndromePD-L1 surface expressionAcute myeloid leukemiaPlatinum-containing chemotherapyPhase 2 studyIntensive chemotherapyArm AMyeloid blastsCelgene CorporationAML ptsMedian OSPD-L1AML cohortDisease progressionSurface expressionTreatment groupsTreatment cyclesECOG performance status 0First large randomized trialLarger phase 2 studiesPD-L1 blocking antibodiesRandomized phase 2 studyConcurrent platinum-based chemotherapyResponse criteriaSafety of azacitidine
2018
Outcomes of Patients with Newly-Diagnosed Acute Myeloid Leukemia and Hyperleukocytosis Who Did Not Undergo Intensive Chemotherapy: Results from a Large International Database
Shallis R, Stahl M, Wei W, Montesinos P, Lengline E, Neukirchen J, Bhatt V, Sekeres M, Fathi A, Konig H, Luger S, Khan I, Roboz G, Cluzeau T, Martínez-Cuadron D, Raffoux E, Germing U, Umakanthan J, Mukherjee S, Brunner A, Miller A, McMahon C, Ritchie E, Rodríguez-Veiga R, Itzykson R, Boluda B, Rabian F, Tormo M, Cruz E, Podoltsev N, Gore S, Zeidan A. Outcomes of Patients with Newly-Diagnosed Acute Myeloid Leukemia and Hyperleukocytosis Who Did Not Undergo Intensive Chemotherapy: Results from a Large International Database. Blood 2018, 132: 3999. DOI: 10.1182/blood-2018-99-119755.Peer-Reviewed Original ResearchTumor lysis syndromeIntensive chemotherapyIntensive care unitOverall survivalClinical evidenceAstex PharmaceuticalsSpeakers bureauDaiichi SankyoMedian OSWorse OSAML patientsPlatelet countEastern Cooperative Oncology Group performance statusJazz PharmaceuticalsCleveland Clinic Taussig Cancer InstituteJanssen PharmaceuticalsOne-year OS probabilityCelgene CorporationAdvisory CommitteeMDS International FoundationPoor-risk AMLBest supportive careLow-dose cytarabineMedian overall survivalOutcomes of patientsHypomethylating agents in relapsed and refractory AML: outcomes and their predictors in a large international patient cohort
Stahl M, DeVeaux M, Montesinos P, Itzykson R, Ritchie EK, Sekeres MA, Barnard JD, Podoltsev NA, Brunner AM, Komrokji RS, Bhatt VR, Al-Kali A, Cluzeau T, Santini V, Fathi AT, Roboz GJ, Fenaux P, Litzow MR, Perreault S, Kim TK, Prebet T, Vey N, Verma V, Germing U, Bergua JM, Serrano J, Gore SD, Zeidan AM. Hypomethylating agents in relapsed and refractory AML: outcomes and their predictors in a large international patient cohort. Blood Advances 2018, 2: 923-932. PMID: 29685952, PMCID: PMC5916007, DOI: 10.1182/bloodadvances.2018016121.Peer-Reviewed Original ResearchConceptsOverall survivalRR-AMLMedian OSOlder acute myeloid leukemia patientsAcute myeloid leukemia patientsCR/CRiIncomplete count recoveryMedian overall survivalDecreased overall survivalBone marrow blastsReasonable therapeutic optionMyeloid leukemia patientsPredictors of responseImproved response ratesLarge international patient cohortInternational patient cohortGood responseComplete remissionHematologic improvementRefractory AMLMarrow blastsMedian ageCount recoveryFrontline treatmentTherapeutic optionsAllogeneic Hematopoietic Stem Cell Transplantation Following the Use of Hypomethylating Agents among Patients with Relapsed or Refractory AML: Findings from an International Retrospective Study
Stahl M, DeVeaux M, Montesinos P, Itzykson R, Ritchie EK, Sekeres MA, Majhail N, Barnard J, Podoltsev NA, Brunner AM, Komrokji RS, Bhatt VR, Al-Kali A, Cluzeau T, Santini V, Roboz GJ, Fenaux P, Litzow M, Fathi AT, Perreault S, Kim TK, Prebet T, Vey N, Verma V, Kobbe G, Bergua J, Serrano J, Gore SD, Zeidan AM. Allogeneic Hematopoietic Stem Cell Transplantation Following the Use of Hypomethylating Agents among Patients with Relapsed or Refractory AML: Findings from an International Retrospective Study. Transplantation And Cellular Therapy 2018, 24: 1754-1758. PMID: 29649620, DOI: 10.1016/j.bbmt.2018.03.025.Peer-Reviewed Original ResearchConceptsHematopoietic stem cell transplantationAllogeneic hematopoietic stem cell transplantationHMA therapyStem cell transplantationComplete remissionCell transplantationUnrelated hematopoietic stem cell transplantationInternational retrospective studyLimited treatment optionsAcute myeloid leukemiaChronic GVHDMedian OSPrimary refractoryRR-AMLConditioning regimenRefractory AMLPatients patientsUnrelated donorsEntire cohortPoor prognosisRetrospective studyTreatment optionsMyeloid leukemiaInternational cohortHypomethylating agent
2017
Hypomethylating agent therapy use and survival in older patients with chronic myelomonocytic leukemia in the United States: A large population‐based study
Zeidan AM, Hu X, Long JB, Wang R, Ma X, Podoltsev NA, Huntington SF, Gore SD, Davidoff AJ. Hypomethylating agent therapy use and survival in older patients with chronic myelomonocytic leukemia in the United States: A large population‐based study. Cancer 2017, 123: 3754-3762. PMID: 28621841, PMCID: PMC6540984, DOI: 10.1002/cncr.30814.Peer-Reviewed Original ResearchConceptsChronic myelomonocytic leukemiaRisk of deathSupportive careEnd Results-Medicare databaseOlder adultsMedian OS timeOverall survival benefitCohort of patientsProportional hazards modelUse of HMAsMedian OSAgent therapySurvival benefitOS timeCMML patientsMyelomonocytic leukemiaHazards modelHMA treatmentPatientsTemporal improvementSecondary analysisPropensity scoreLimited evidenceSurvival changesApproval
2016
Differential response to hypomethylating agents based on sex: a report on behalf of the MDS Clinical Research Consortium (MDS CRC)*
DeZern AE, Zeidan AM, Barnard J, Hand W, Al Ali N, Brown F, Zimmerman C, Roboz GJ, Garcia-Manero G, Steensma DP, Komrokji RS, Sekeres MA. Differential response to hypomethylating agents based on sex: a report on behalf of the MDS Clinical Research Consortium (MDS CRC)*. Leukemia & Lymphoma 2016, 58: 1325-1331. PMID: 27774847, PMCID: PMC5394924, DOI: 10.1080/10428194.2016.1246726.Peer-Reviewed Original ResearchConceptsHigh-risk myelodysplastic syndromeMyelodysplastic syndromeOverall survivalFemale patientsMDS Clinical Research ConsortiumLonger median OSFirst-line therapyClinical Research ConsortiumMedian OSBetter OSPatient sexCytidine deaminase activityPatientsResponse rateDifferential response ratesSignificant differencesSexResearch ConsortiumDeaminase activityDifferential responseBiological reasonsSyndromeTherapyDecitabineDifferences
2015
Differential Response to Hypomethylating Agents Based on Sex: A Report on Behalf of the MDS Clinical Research Consortium (MDS CRC)
DeZern A, Zeidan A, Barnard J, Hand W, Al Ali N, Brown F, Zimmerman C, Roboz G, Komrokji R, Garcia-Manero G, Steensma D, Sekeres M. Differential Response to Hypomethylating Agents Based on Sex: A Report on Behalf of the MDS Clinical Research Consortium (MDS CRC). Blood 2015, 126: 2889. DOI: 10.1182/blood.v126.23.2889.2889.Peer-Reviewed Original ResearchHigh-risk myelodysplastic syndromeMedian overall survivalBone marrow blastsFirst-line therapyOverall survivalTime of presentationMyelodysplastic syndromeMedian OSBlast percentageBetter OSMarrow blastsCytogenetic categoriesBone marrow blast percentageMDS Clinical Research ConsortiumStandard first-line therapyInternational Working Group criteriaCox PH analysisCox proportional analysisMarrow blast percentageSpeakers bureauClinical Research ConsortiumLog-rank testDate of deathFuture prospective investigationsMann-Whitney U testComparative Effectiveness of Azacitidine Versus Decitabine Among Older Adults Diagnosed with Higher-Risk Myelodysplastic Syndromes (HR-MDS)
Zeidan A, Long J, Hall J, Wang R, Huntington S, Abel G, Prebet T, Podoltsev N, Gross C, Gore S, Ma X, Davidoff A. Comparative Effectiveness of Azacitidine Versus Decitabine Among Older Adults Diagnosed with Higher-Risk Myelodysplastic Syndromes (HR-MDS). Blood 2015, 126: 3285. DOI: 10.1182/blood.v126.23.3285.3285.Peer-Reviewed Original ResearchHigh-risk myelodysplastic syndromeHR-MDS patientsKaplan-Meier survival curvesEnd of studyHMA initiationMedian OSClinical trialsComorbidity countHazard ratioHigh school educationClinical practiceMultivariate Cox proportional hazards modelSurvival curvesEnd Results-Medicare databaseMedian household incomeRandomized phase III trialReal-world clinical practiceCox proportional hazards modelOlder MDS patientsDisability Status ScoreRetrospective cohort studyOverall survival advantagePhase III trialsYear of diagnosisErythropoiesis-stimulating agentsComparison of risk stratification tools in predicting outcomes of patients with higher-risk myelodysplastic syndromes treated with azanucleosides
Zeidan AM, Sekeres MA, Garcia-Manero G, Steensma DP, Zell K, Barnard J, Ali NA, Zimmerman C, Roboz G, DeZern A, Nazha A, Jabbour E, Kantarjian H, Gore SD, Maciejewski JP, List A, Komrokji R. Comparison of risk stratification tools in predicting outcomes of patients with higher-risk myelodysplastic syndromes treated with azanucleosides. Leukemia 2015, 30: 649-657. PMID: 26464171, PMCID: PMC4775363, DOI: 10.1038/leu.2015.283.Peer-Reviewed Original ResearchConceptsInternational Prognostic Scoring SystemPrognostic scoring systemMD Anderson Prognostic Scoring SystemMyelodysplastic syndromePrognostic toolScoring systemDifferent prognostic scoring systemsHigh-risk myelodysplastic syndromeRelative prognostic performanceOutcomes of patientsFirst-line therapyRisk stratification toolHigh-risk groupWorld Health OrganizationHR-MDSMedian OSObjective responseOverall survivalStandard therapyPrognostic utilityStratification toolPatient cohortPrognostic performancePatientsHealth Organization