2024
Oral decitabine–cedazuridine versus intravenous decitabine for myelodysplastic syndromes and chronic myelomonocytic leukaemia (ASCERTAIN): a registrational, randomised, crossover, pharmacokinetics, phase 3 study
Garcia-Manero G, McCloskey J, Griffiths E, Yee K, Zeidan A, Al-Kali A, Deeg H, Patel P, Sabloff M, Keating M, Zhu N, Gabrail N, Fazal S, Maly J, Odenike O, Kantarjian H, DeZern A, O'Connell C, Roboz G, Busque L, Buckstein R, Amin H, Randhawa J, Leber B, Shastri A, Dao K, Oganesian A, Hao Y, Keer H, Azab M, Savona M. Oral decitabine–cedazuridine versus intravenous decitabine for myelodysplastic syndromes and chronic myelomonocytic leukaemia (ASCERTAIN): a registrational, randomised, crossover, pharmacokinetics, phase 3 study. The Lancet Haematology 2024, 11: e15-e26. PMID: 38135371, DOI: 10.1016/s2352-3026(23)00338-1.Peer-Reviewed Original ResearchConceptsChronic myelomonocytic leukemiaIntravenous decitabineMyelodysplastic syndromeMyelomonocytic leukemiaOral therapyPrimary endpointAdverse eventsEastern Cooperative Oncology Group performance status 0Treatment cyclesCycle 1Full treatment dosePerformance status 0Treatment-related deathsFrequent adverse eventsSerious adverse eventsPhase 3 studyPhase 3 trialPotential treatment benefitsCommunity-based clinicsAcute myeloid leukemiaNext treatment cycleTreatment of individualsOral decitabineStatus 0Treatment discontinuation
2023
Oral therapy for myelodysplastic syndromes/neoplasms and acute myeloid leukemia: a revolution in progress
Venugopal S, Shallis R, Zeidan A. Oral therapy for myelodysplastic syndromes/neoplasms and acute myeloid leukemia: a revolution in progress. Expert Review Of Anticancer Therapy 2023, 23: 903-911. PMID: 37470508, DOI: 10.1080/14737140.2023.2238897.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsMeSH KeywordsAzacitidineDecitabineHumansLeukemia, Myeloid, AcuteMyelodysplastic SyndromesQuality of LifeConceptsAcute myeloid leukemiaOral therapyMyeloid leukemiaAllogeneic hematopoietic stem cell transplantationHematopoietic stem cell transplantationDisease-related complicationsDisease-directed therapyStem cell transplantationQuality of lifeCC-486HR-MDSOral azacitidineClinic visitsMost patientsGood tolerabilityIntensive therapyOptimal regimensCell transplantationTherapy combinationsTreatment optionsMedication administrationPatient outcomesMyeloid neoplasmsClinical developmentMyeloid malignancies
2022
Prospective comparison of outcomes with azacitidine and decitabine in patients with AML ineligible for intensive chemotherapy
Zeidan AM, Fenaux P, Gobbi M, Mayer J, Roboz GJ, Krauter J, Robak T, Kantarjian HM, Novák J, Jedrzejczak WW, Thomas X, Ojeda-Uribe M, Miyazaki Y, Min YH, Yeh SP, Brandwein JM, Gercheva L, Demeter J, Griffiths EA, Yee KWL, Issa JJ, Bewersdorf JP, Keer H, Hao Y, Azab M, Döhner H. Prospective comparison of outcomes with azacitidine and decitabine in patients with AML ineligible for intensive chemotherapy. Blood 2022, 140: 285-289. PMID: 35507690, PMCID: PMC9305088, DOI: 10.1182/blood.2022015832.Peer-Reviewed Original ResearchImpact of Hypomethylating Agent Use on Hospital and Emergency Room Visits, and Predictors of Early Discontinuation in Patients With Higher-Risk Myelodysplastic Syndromes
Zeidan AM, Joshi N, Kale H, Wang WJ, Corman S, Salimi T, Epstein RS. Impact of Hypomethylating Agent Use on Hospital and Emergency Room Visits, and Predictors of Early Discontinuation in Patients With Higher-Risk Myelodysplastic Syndromes. Clinical Lymphoma Myeloma & Leukemia 2022, 22: 670-679. PMID: 35614009, DOI: 10.1016/j.clml.2022.04.016.Peer-Reviewed Original ResearchConceptsHigh-risk myelodysplastic syndromeHMA therapyPoor performance statusRate of hospitalizationSEER-Medicare databaseMyelodysplastic syndromeER visitsEarly discontinuationPerformance statusEmergency roomOlder agePredictors of discontinuationEmergency room visitsHigh-risk groupHigh economic burdenTreatment discontinuationExcess blastsMore hospitalizationsNew hospitalizationRefractory anemiaRoom visitsHigh riskDiscontinuationMD diagnosisAgent use
2020
A Phase Ib Study of Onvansertib, a Novel Oral PLK1 Inhibitor, in Combination Therapy for Patients with Relapsed or Refractory Acute Myeloid Leukemia
Zeidan AM, Ridinger M, Lin TL, Becker PS, Schiller GJ, Patel PA, Spira AI, Tsai ML, Samuëlsz E, Silberman SL, Erlander M, Wang ES. A Phase Ib Study of Onvansertib, a Novel Oral PLK1 Inhibitor, in Combination Therapy for Patients with Relapsed or Refractory Acute Myeloid Leukemia. Clinical Cancer Research 2020, 26: 6132-6140. PMID: 32998961, DOI: 10.1158/1078-0432.ccr-20-2586.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAntineoplastic Combined Chemotherapy ProtocolsCytarabineDecitabineDrug Resistance, NeoplasmFemaleFollow-Up StudiesHumansLeukemia, Myeloid, AcuteMaleMaximum Tolerated DoseMiddle AgedNeoplasm Recurrence, LocalPiperazinesPrognosisPyrazolesQuinazolinesSalvage TherapyConceptsAcute myeloid leukemiaPhase Ib studyMyeloid leukemiaIb studyRefractory (R/R) AMLFirst-cycle dose-limiting toxicitiesRefractory acute myeloid leukemiaOngoing phase II trialAntileukemic activityMost grade 3Low-dose cytarabinePhase II trialBone marrow blastsDose-limiting toxicityPLK1 inhibitorsPolo-like kinase 1Evaluable patientsExploratory endpointsComplete remissionII trialPrimary endpointAdverse eventsClinical responseMarrow blastsCount recoveryPhase 1 dose escalation trial of volasertib in combination with decitabine in patients with acute myeloid leukemia
Cortes J, Podoltsev N, Kantarjian H, Borthakur G, Zeidan AM, Stahl M, Taube T, Fagan N, Rajeswari S, Uy GL. Phase 1 dose escalation trial of volasertib in combination with decitabine in patients with acute myeloid leukemia. International Journal Of Hematology 2020, 113: 92-99. PMID: 32951163, DOI: 10.1007/s12185-020-02994-8.Peer-Reviewed Original ResearchMeSH KeywordsAgedAntineoplastic Combined Chemotherapy ProtocolsCell Cycle ProteinsDecitabineDose-Response Relationship, DrugFebrile NeutropeniaFeeding and Eating DisordersFemaleGene ExpressionHumansLeukemia, Myeloid, AcuteMaleMolecular Targeted TherapyProtein Serine-Threonine KinasesProto-Oncogene ProteinsPteridinesTreatment OutcomeConceptsAcute myeloid leukemiaMyeloid leukemiaCommon treatment-emergent adverse eventsPhase 1 dose-escalation trialTreatment-emergent adverse eventsMTD of volasertibObjective response rateAdverse event profileDose-escalation trialPhase 1 trialAnti-leukemic activityPolo-like kinase 1Febrile neutropeniaEscalation trialAdverse eventsCell cycle kinase inhibitorsAML patientsEvent profilePoor prognosisResponse ratePatientsVolasertibDecitabineKinase inhibitorsNumerous cancersClinical outcomes of older patients with AML receiving hypomethylating agents: a large population-based study in the United States
Zeidan AM, Wang R, Wang X, Shallis RM, Podoltsev NA, Bewersdorf JP, Huntington SF, Neparidze N, Giri S, Gore SD, Davidoff AJ, Ma X. Clinical outcomes of older patients with AML receiving hypomethylating agents: a large population-based study in the United States. Blood Advances 2020, 4: 2192-2201. PMID: 32433746, PMCID: PMC7252544, DOI: 10.1182/bloodadvances.2020001779.Peer-Reviewed Original ResearchConceptsAcute myeloid leukemiaDecitabine-treated patientsTransfusion independenceRed blood cell transfusion independenceLarge population-based studyOlder AML patientsRBC transfusion independenceEnd Results-MedicarePopulation-based studyStandard of careAgent azacitidineMedian survivalOlder patientsIntensive therapyAML patientsClinical outcomesClinical benefitMyeloid leukemiaMortality riskPatientsAzacitidineDecitabineOlder adultsOne-thirdMeaningful differences
2019
RBC transfusion independence among lower risk MDS patients receiving hypomethylating agents: a population-level analysis
Zeidan AM, Zhu W, Stahl M, Wang R, Huntington SF, Giri S, Podoltsev NA, Gore SD, Ma X, Davidoff AJ. RBC transfusion independence among lower risk MDS patients receiving hypomethylating agents: a population-level analysis. Leukemia & Lymphoma 2019, 60: 3181-3187. PMID: 31170846, DOI: 10.1080/10428194.2019.1622700.Peer-Reviewed Original ResearchConceptsRBC transfusion independenceLR-MDS patientsTransfusion independenceHMA initiationRBC transfusionClinical effectivenessReal-life clinical effectivenessRed blood cell transfusionLower-risk myelodysplastic syndromesLow-risk MDS patientsRisk MDS patientsBlood cell transfusionRisk myelodysplastic syndromesHMA therapyLR-MDSCell transfusionMost patientsDisease courseMDS patientsMedicare databaseMyelodysplastic syndromePopulation-level estimatesLower oddsTransfusionPatients
2018
Hypomethylating 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 options
2017
Long-term survival of older patients with MDS treated with HMA therapy without subsequent stem cell transplantation
Zeidan AM, Stahl M, Hu X, Wang R, Huntington SF, Podoltsev NA, Gore SD, Ma X, Davidoff AJ. Long-term survival of older patients with MDS treated with HMA therapy without subsequent stem cell transplantation. Blood 2017, 131: 818-821. PMID: 29259002, PMCID: PMC6410557, DOI: 10.1182/blood-2017-10-811729.Peer-Reviewed Original ResearchA call for action: Increasing enrollment of untreated patients with higher‐risk myelodysplastic syndromes in first‐line clinical trials
Zeidan AM, Stahl M, Sekeres MA, Steensma DP, Komrokji RS, Gore SD. A call for action: Increasing enrollment of untreated patients with higher‐risk myelodysplastic syndromes in first‐line clinical trials. Cancer 2017, 123: 3662-3672. PMID: 28759108, DOI: 10.1002/cncr.30903.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsHigh-risk myelodysplastic syndromeAZA-001 trialClinical trialsMinimal survival gainsLarge randomized trialsManagement of patientsPopulation-based studyClinical trial enrollmentQuality of lifeMonotherapy armMedian survivalRandomized trialsSurvival impactTrial enrollmentSurvival gainMyelodysplastic syndromeRegistry analysisAggressive malignancyPatientsNatural historyRoutine useTrialsSurvivalEnrollmentHMAsHypomethylating 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 reasonsSyndromeTherapyDecitabineDifferencesComparative clinical effectiveness of azacitidine versus decitabine in older patients with myelodysplastic syndromes
Zeidan AM, Davidoff AJ, Long JB, Hu X, Wang R, Ma X, Gross CP, Abel GA, Huntington SF, Podoltsev NA, Hajime U, Prebet T, Gore SD. Comparative clinical effectiveness of azacitidine versus decitabine in older patients with myelodysplastic syndromes. British Journal Of Haematology 2016, 175: 829-840. PMID: 27650975, DOI: 10.1111/bjh.14305.Peer-Reviewed Original ResearchConceptsMyelodysplastic syndromeRAEB patientsMedian survivalClinical trialsMultivariate Cox proportional hazards modelCox proportional hazards modelKaplan-Meier methodPopulation-based survivalSignificant survival differenceComparative clinical effectivenessProportional hazards modelAgent azacitidineHMA initiationExcess blastsOlder patientsRandomized trialsHistological subtypesRefractory anemiaClinical effectivenessSurvival differencesSubset analysisSurvival advantageHazards modelPatientsDecitabine
2015
Comparison 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