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
Consensus proposal for revised International Working Group 2023 response criteria for higher-risk myelodysplastic syndromes
Zeidan A, Platzbecker U, Bewersdorf J, Stahl M, Adès L, Borate U, Bowen D, Buckstein R, Brunner A, Carraway H, Daver N, Díez-Campelo M, de Witte T, DeZern A, Efficace F, Garcia-Manero G, Garcia J, Germing U, Giagounidis A, Griffiths E, Hasserjian R, Hellström-Lindberg E, Iastrebner M, Komrokji R, Kulasekararaj A, Malcovati L, Miyazaki Y, Odenike O, Santini V, Sanz G, Scheinberg P, Stauder R, van de Loosdrecht A, Wei A, Sekeres M, Fenaux P. Consensus proposal for revised International Working Group 2023 response criteria for higher-risk myelodysplastic syndromes. Blood 2023, 141: 2047-2061. PMID: 36724453, DOI: 10.1182/blood.2022018604.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsMeSH KeywordsConsensusHematologyHumansMyelodysplastic SyndromesOutcome Assessment, Health CareTreatment OutcomeConceptsHigh-risk MDSComplete remissionResponse criteriaInternational Working GroupClinical trialsHigh-risk myelodysplastic syndromeEnd pointMarrow complete remissionPartial hematologic recoveryClinical end pointsPatient-centered outcomesNovel investigational drugsVariable clinical presentationEvent end pointsHemoglobin thresholdHematologic recoveryCount recoveryClinical presentationClinical benefitMyelodysplastic syndromeIWG criteriaMyelodysplastic neoplasmsConsensus recommendationsInvestigational drugsNew agentsTreatment patterns and real-world effectiveness of rituximab maintenance in older patients with mantle cell lymphoma: a population-based analysis
Di M, Long J, Kothari S, Sethi T, Zeidan A, Podoltsev N, Shallis R, Wang R, Ma X, Huntington S. Treatment patterns and real-world effectiveness of rituximab maintenance in older patients with mantle cell lymphoma: a population-based analysis. Haematologica 2023, 108: 2218-2223. PMID: 36655436, PMCID: PMC10388284, DOI: 10.3324/haematol.2022.282252.Peer-Reviewed Original Research
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 ResearchMeSH KeywordsAdultAgedAged, 80 and overHumansMiddle AgedMyelodysplastic SyndromesRemission InductionTreatment OutcomeYoung AdultConceptsPartial 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 survivalPatientsTherapyA phase 1b study of venetoclax and azacitidine combination in patients with relapsed or refractory myelodysplastic syndromes
Zeidan AM, Borate U, Pollyea DA, Brunner AM, Roncolato F, Garcia JS, Filshie R, Odenike O, Watson AM, Krishnadasan R, Bajel A, Naqvi K, Zha J, Cheng W, Zhou Y, Hoffman D, Harb JG, Potluri J, Garcia‐Manero G. A phase 1b study of venetoclax and azacitidine combination in patients with relapsed or refractory myelodysplastic syndromes. American Journal Of Hematology 2022, 98: 272-281. PMID: 36309981, PMCID: PMC10100228, DOI: 10.1002/ajh.26771.Peer-Reviewed Original ResearchConceptsMedian overall survivalMyelodysplastic syndromeOverall survivalTransfusion independenceHematological improvementTherapy failureHigh-risk myelodysplastic syndromeInternational Working Group criteriaHematological adverse eventsPhase 1b studyRefractory myelodysplastic syndromeStandard of careEfficacy of venetoclaxEffective therapeutic strategyFebrile neutropeniaMarrow CROral venetoclaxComplete remissionAdverse eventsMedian durationAzacitidine treatmentMedian timeMarrow responseMulticenter studyGroup criteriaProspective 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 ResearchA phase I/II multicenter, open-label, dose escalation and randomized trial of BI 836858 in patients with low- or intermediate-1-risk myelodysplastic syndrome.
Komrokji RS, Carraway HE, Germing U, Wermke M, Zeidan AM, Fu E, Rüter B, Burkard U, Osswald A, Foran JM. A phase I/II multicenter, open-label, dose escalation and randomized trial of BI 836858 in patients with low- or intermediate-1-risk myelodysplastic syndrome. Haematologica 2022, 107: 2742-2747. PMID: 35734924, PMCID: PMC9614517, DOI: 10.3324/haematol.2021.280500.Peer-Reviewed Original ResearchA phase 1b study of glasdegib + azacitidine in patients with untreated acute myeloid leukemia and higher-risk myelodysplastic syndromes
Sekeres MA, Schuster M, Joris M, Krauter J, Maertens J, Breems D, Gyan E, Kovacsovics T, Verma A, Vyas P, Wang ES, Ching K, O’Brien T, Gallo Stampino C, Ma WW, Kudla A, Chan G, Zeidan AM. A phase 1b study of glasdegib + azacitidine in patients with untreated acute myeloid leukemia and higher-risk myelodysplastic syndromes. Annals Of Hematology 2022, 101: 1689-1701. PMID: 35488900, DOI: 10.1007/s00277-022-04853-4.Peer-Reviewed Original ResearchConceptsAcute myeloid leukemiaHigh-risk myelodysplastic syndromePhase 1b studyChronic myelomonocytic leukemiaMyelodysplastic syndromeExpansion cohortSafety profileMDS cohortMyeloid leukemiaTreatment-emergent adverse eventsUntreated acute myeloid leukemiaNon-hematologic gradeMedian overall survivalAcceptable safety profileOverall response rateDrug-drug interactionsSafety cohortIntensive chemotherapyAdverse eventsOverall survivalClinical benefitQT prolongationAML cohortMyelomonocytic leukemiaGlasdegibImpact 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
2021
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
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 monotherapyInjectable Hypomethylating Agents for Management of Myelodysplastic Syndromes: Patients’ Perspectives on Treatment
Zeidan AM, Jayade S, Schmier J, Botteman M, Hassan A, Ruiters D, Hill K, Joshi N. Injectable Hypomethylating Agents for Management of Myelodysplastic Syndromes: Patients’ Perspectives on Treatment. Clinical Lymphoma Myeloma & Leukemia 2021, 22: e185-e198. PMID: 34674983, DOI: 10.1016/j.clml.2021.09.009.Peer-Reviewed Original ResearchConceptsMDS patientsAdult MDS patientsMedian patient agePain/discomfortMost MDS patientsOnline cross-sectional surveyDaily activitiesCross-sectional surveyPatient advocacy groupsPatient ageMyelodysplastic syndromeSC administrationSubcutaneous administrationTreatment administrationSC therapyTreatment challengesPatient's perspectiveHypomethylating agentRisk scoreHMA treatmentMD treatmentPatientsAdministrationAzacitidinePain
2020
Phase 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 ResearchMeSH KeywordsAgedDecitabineHumansLeukemia, Myeloid, AcuteMedicareRetrospective StudiesTreatment OutcomeUnited StatesConceptsAcute 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 oddsTransfusionPatientsImpact of Hydroxyurea on Survival and Risk of Thrombosis Among Older Patients With Essential Thrombocythemia.
Podoltsev NA, Zhu M, Zeidan AM, Wang R, Wang X, Davidoff AJ, Huntington SF, Giri S, Gore SD, Ma X. Impact of Hydroxyurea on Survival and Risk of Thrombosis Among Older Patients With Essential Thrombocythemia. Journal Of The National Comprehensive Cancer Network 2019, 17: 211-219. PMID: 30865915, DOI: 10.6004/jnccn.2018.7095.Peer-Reviewed Original ResearchConceptsImpact of hydroxyureaThrombotic eventsEssential thrombocythemiaEffect of hydroxyureaOlder patientsOverall survivalLower riskMultivariable Cox proportional hazards regression modelsCox proportional hazards regression modelHigh-risk essential thrombocythemiaProportional hazards regression modelsRetrospective cohort studyRisk of deathSEER-Medicare databaseHazards regression modelsRisk of thrombosisHU usersFrontline therapyCohort studyCurrent guidelinesStudy populationPatientsReal-world settingThrombosisOlder adultsTreatment sequence of lenalidomide and hypomethylating agents and the impact on clinical outcomes for patients with myelodysplastic syndromes
Zeidan AM, Klink AJ, McGuire M, Feinberg B. Treatment sequence of lenalidomide and hypomethylating agents and the impact on clinical outcomes for patients with myelodysplastic syndromes. Leukemia & Lymphoma 2019, 60: 2050-2055. PMID: 30636526, DOI: 10.1080/10428194.2018.1551538.Peer-Reviewed Original ResearchConceptsMyelodysplastic syndromeFirst-line useLonger treatment durationAgent azacitidineTreatment discontinuationClinical outcomesMedian timeInsurance disenrollmentUS payersTreatment durationLenalidomidePatientsTreatment sequenceOptimal sequencingSyndromeSurvivalOutcomesDiscontinuationAzacitidineDecitabineDisenrollment
2018
Oncologist volume and outcomes in older adults diagnosed with diffuse large B cell lymphoma
Huntington SF, Hoag JR, Zhu W, Wang R, Zeidan AM, Giri S, Podoltsev NA, Gore SD, Ma X, Gross CP, Davidoff AJ. Oncologist volume and outcomes in older adults diagnosed with diffuse large B cell lymphoma. Cancer 2018, 124: 4211-4220. PMID: 30216436, PMCID: PMC6263848, DOI: 10.1002/cncr.31688.Peer-Reviewed Original ResearchConceptsDiffuse large B-cell lymphomaLarge B-cell lymphomaB-cell lymphomaOlder adultsCell lymphomaPopulation-based cohort analysisHigh-quality cancer careAnthracycline-containing regimenGuideline-adherent therapyHigh-volume providersNumber of patientsLook-back periodCytotoxic regimensSystemic therapyImproved survivalClinical outcomesReduced hospitalizationsLymphoma patientsCancer careCohort analysisMedicare beneficiariesComplex surgeryDLBCL casesLymphomaClinical volumeA Multi-center Phase I Trial of Ipilimumab in Patients with Myelodysplastic Syndromes following Hypomethylating Agent Failure
Zeidan AM, Knaus HA, Robinson TM, Towlerton AMH, Warren EH, Zeidner JF, Blackford AL, Duffield AS, Rizzieri D, Frattini MG, Levy YM, Schroeder MA, Ferguson A, Sheldon KE, DeZern AE, Gojo I, Gore SD, Streicher H, Luznik L, Smith BD. A Multi-center Phase I Trial of Ipilimumab in Patients with Myelodysplastic Syndromes following Hypomethylating Agent Failure. Clinical Cancer Research 2018, 24: 3519-3527. PMID: 29716921, PMCID: PMC6680246, DOI: 10.1158/1078-0432.ccr-17-3763.Peer-Reviewed Original ResearchConceptsImmune-related adverse eventsMarrow complete responseMyelodysplastic syndromeGrade 2T cellsHigher immune-related adverse eventsHigh-risk myelodysplastic syndromeT-cell receptor sequencingRisk myelodysplastic syndromesInvestigator-initiated trialClin Cancer ResDrug discontinuationHMA failureStable diseaseSystemic steroidsAdverse eventsMedian survivalComplete responseDismal survivalAdditional patientsClinical benefitTreatment optionsExcessive toxicityPatientsDose levelsPerformance of the Medical Research Council (MRC) and the Leukemia Research Foundation (LRF) score in predicting survival benefit with hypomethylating agent use in patients with relapsed or refractory acute myeloid leukemia
Stahl M, DeVeaux M, Montesinos P, Itzykson R, Ritchie EK, Sekeres MA, Barnard J, Podoltsev NA, Brunner A, 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, Germing U, Bergua J, Serrano J, Gore SD, Zeidan AM. Performance of the Medical Research Council (MRC) and the Leukemia Research Foundation (LRF) score in predicting survival benefit with hypomethylating agent use in patients with relapsed or refractory acute myeloid leukemia. Leukemia & Lymphoma 2018, 60: 246-249. PMID: 29963936, DOI: 10.1080/10428194.2018.1468893.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAdultAgedAged, 80 and overAntineoplastic Combined Chemotherapy ProtocolsDrug Resistance, NeoplasmFemaleHematopoietic Stem Cell TransplantationHumansLeukemia, Myeloid, AcuteMaleMiddle AgedNeoplasm Recurrence, LocalPrognosisRetrospective StudiesRisk AssessmentRisk FactorsSurvival AnalysisTransplantation, HomologousTreatment OutcomeYoung AdultCounseling patients with higher-risk MDS regarding survival with azacitidine therapy: are we using realistic estimates?
Zeidan AM, Stahl M, DeVeaux M, Giri S, Huntington S, Podoltsev N, Wang R, Ma X, Davidoff AJ, Gore SD. Counseling patients with higher-risk MDS regarding survival with azacitidine therapy: are we using realistic estimates? Blood Cancer Journal 2018, 8: 55. PMID: 29891916, PMCID: PMC5995881, DOI: 10.1038/s41408-018-0081-8.Peer-Reviewed Original Research