2024
Intensive induction chemotherapy vs hypomethylating agents in combination with venetoclax in NPM1-mutant AML
Bewersdorf J, Shimony S, Shallis R, Liu Y, Berton G, Schaefer E, Zeidan A, Goldberg A, Stein E, Marcucci G, Bystrom R, Lindsley R, Chen E, Perez J, Stein A, Pullarkat V, Aldoss I, DeAngelo D, Neuberg D, Stone R, Garciaz S, Ball B, Stahl M. Intensive induction chemotherapy vs hypomethylating agents in combination with venetoclax in NPM1-mutant AML. Blood Advances 2024, 8: 4845-4855. PMID: 38941537, PMCID: PMC11416634, DOI: 10.1182/bloodadvances.2024012858.Peer-Reviewed Original ResearchIntensive induction chemotherapyAcute myeloid leukemiaNPM1-Mutant Acute Myeloid LeukemiaInduction chemotherapyHypomethylating agentsMulticenter retrospective cohort study of patientsPatients treated with ICAllogeneic stem cell transplantationRetrospective cohort study of patientsMulticenter retrospective cohort studyCohort study of patientsComposite complete remissionStem cell transplantationYears-oldFLT3-ITD mutationStudy of patientsStandard of careNormal cytogeneticsComplete remissionCell transplantationNPM1 mutationsMyeloid leukemiaFLT3-ITDYounger patientsOlder patientsAcute myeloid leukemia (AML) with chromosome 3 inversion: biology, management, and clinical outcome
Alhajahjeh A, Bewersdorf J, Bystrom R, Zeidan A, Shimony S, Stahl M. Acute myeloid leukemia (AML) with chromosome 3 inversion: biology, management, and clinical outcome. Leukemia & Lymphoma 2024, ahead-of-print: 1-11. PMID: 38962996, DOI: 10.1080/10428194.2024.2367040.Peer-Reviewed Original ResearchAcute myeloid leukemiaIntensive chemotherapyHypomethylating agentsMyeloid leukemiaAllogeneic stem cell transplantationAcute myeloid leukemia casesAcute myeloid leukemia subtypesStem cell transplantationComplex hematological malignancyCurrent treatment modalitiesRare genetic anomalyCell transplantationHematologic malignanciesTreatment modalitiesClinical outcomesTreatment responseInv(3Genetic alterationsLeukemia developmentTreatment strategiesCellular processesGenetic anomaliesLeukemiaFusion geneClinical implicationsPrognostic impact of 'multi-hit' versus 'single hit' TP53 alteration in patients with acute myeloid leukemia: results from the Consortium on Myeloid Malignancies and Neoplastic Diseases.
Badar T, Nanaa A, Atallah E, Shallis R, Craver E, Li Z, Goldberg A, Saliba A, Patel A, Bewersdorf J, Duvall A, Burkart M, Bradshaw D, Abaza Y, Stahl M, Palmisiano N, Murthy G, Zeidan A, Kota V, Patnaik M, Litzow M. Prognostic impact of 'multi-hit' versus 'single hit' TP53 alteration in patients with acute myeloid leukemia: results from the Consortium on Myeloid Malignancies and Neoplastic Diseases. Haematologica 2024 PMID: 38813716, DOI: 10.3324/haematol.2024.285000.Peer-Reviewed Original ResearchAcute myeloid leukemiaMyelodysplastic syndromeComplex cytogeneticsMyeloid leukemiaAllogeneic hematopoietic stem cell transplantationLower-risk myelodysplastic syndromesHematopoietic stem cell transplantationHigher-risk myelodysplastic syndromesOutcomes of SHStem cell transplantationAllo-HCTTP53 alterationsPrognostic impactMyeloid malignanciesTP53 mutationsCell transplantationFLT3-ITDIDH1 mutationMultivariate analysisSupportive careUS academic institutionsNeoplastic diseasePatientsSuperior EFSPredicting outcomeDifferentiation syndrome associated with treatment with IDH2 inhibitor enasidenib: pooled analysis from clinical trials
Montesinos P, Fathi A, de Botton S, Stein E, Zeidan A, Zhu Y, Prebet T, Vigil C, Bluemmert I, Yu X, DiNardo C. Differentiation syndrome associated with treatment with IDH2 inhibitor enasidenib: pooled analysis from clinical trials. Blood Advances 2024, 8: 2509-2519. PMID: 38507688, PMCID: PMC11131052, DOI: 10.1182/bloodadvances.2023011914.Peer-Reviewed Original ResearchAcute myeloid leukemiaDevelopment of differentiation syndromeRisk factorsPooled analysisIDH2-mutant acute myeloid leukemiaClinical trialsAcute myeloid leukemia populationMedian time to onsetClinical features of DSBone marrow blastsNon-specific symptomsTime to onsetBaseline risk factorsTreatment of DSSymptoms of DSIdentified risk factorsFeatures of DSMarrow blastsSystemic steroidsPulmonary infiltratesClinical responseMutant IDH2 inhibitorMyeloid leukemiaClinical featuresGrade 3Cost-effectiveness of adding quizartinib to induction chemotherapy for patients with FLT3-mutant acute myeloid leukemia
Bewersdorf J, Patel K, Shallis R, Podoltsev N, Kewan T, Stempel J, Mendez L, Stahl M, Stein E, Huntington S, Goshua G, Zeidan A. Cost-effectiveness of adding quizartinib to induction chemotherapy for patients with FLT3-mutant acute myeloid leukemia. Leukemia & Lymphoma 2024, 65: 1136-1144. PMID: 38648559, PMCID: PMC11265977, DOI: 10.1080/10428194.2024.2344052.Peer-Reviewed Original ResearchQuality-adjusted life yearsCompletion of consolidation therapyFLT3-mutant acute myeloid leukemiaAllogeneic hematopoietic cell transplantationIncremental cost-effectiveness ratioProbabilistic sensitivity analysesImproved overall survivalHematopoietic cell transplantationPartitioned survival analysis modelAcute myeloid leukemiaCost-effectiveness ratioFLT3 inhibitor quizartinibHealth economic implicationsConsolidation therapyInduction chemotherapyAverage wholesale priceOverall survivalCell transplantationContinuous therapyMyeloid leukemiaITD mutationQuizartinibIncremental costCost-effective optionLife yearsClinical activity, pharmacokinetics, and pharmacodynamics of oral hypomethylating agents for myelodysplastic syndromes/neoplasms and acute myeloid leukemia: A multidisciplinary review
Haumschild R, Kennerly-Shah J, Barbarotta L, Zeidan A. Clinical activity, pharmacokinetics, and pharmacodynamics of oral hypomethylating agents for myelodysplastic syndromes/neoplasms and acute myeloid leukemia: A multidisciplinary review. Journal Of Oncology Pharmacy Practice 2024, 30: 721-736. PMID: 38509812, PMCID: PMC11118786, DOI: 10.1177/10781552241238979.Peer-Reviewed Original ResearchOral hypomethylating agentsAcute myeloid leukemiaHypomethylating agentsPK-PD profilesPharmacokinetic (PK)-pharmacodynamicMyeloid leukemiaTreatment selectionPK-PDConcentration-time curveIntravenous (IVImprove treatment outcomesCC-486IV decitabineOral azacitidineMaintenance therapySubcutaneous azacitidineNo significant differenceImprove quality of lifeAzacitidineClinical trialsClinical activityTreatment outcomesDisease settingsDecitabineDisease outcomeComparing venetoclax in combination with hypomethylating agents to hypomethylating agent-based therapies for treatment naive TP53-mutated acute myeloid leukemia: results from the Consortium on Myeloid Malignancies and Neoplastic Diseases (COMMAND)
Badar T, Nanaa A, Atallah E, Shallis R, Guilherme S, Goldberg A, Saliba A, Patel A, Bewersdorf J, DuVall A, Bradshaw D, Abaza Y, Murthy G, Palmisiano N, Zeidan A, Kota V, Litzow M. Comparing venetoclax in combination with hypomethylating agents to hypomethylating agent-based therapies for treatment naive TP53-mutated acute myeloid leukemia: results from the Consortium on Myeloid Malignancies and Neoplastic Diseases (COMMAND). Blood Cancer Journal 2024, 14: 32. PMID: 38378617, PMCID: PMC10879201, DOI: 10.1038/s41408-024-01000-2.Peer-Reviewed Original Research
2023
Are We Ready For “Triplet” Therapy in Higher-Risk MDS?
Brunner A, Platzbecker U, DeZern A, Zeidan A. Are We Ready For “Triplet” Therapy in Higher-Risk MDS? Clinical Hematology International 2023, 5: 23-32. PMID: 37933301, PMCID: PMC10625655, DOI: 10.46989/001c.88301.Peer-Reviewed Original ResearchAcute myeloid leukemiaCombination chemotherapyPatient populationOnly disease-modifying therapyNovel combination chemotherapyOngoing therapeutic challengeOlder patient populationUnique patient populationDisease-modifying therapiesCurrent treatment paradigmsTherapeutic challengeTreatment paradigmEffective therapyMyeloid leukemiaNew therapiesAppropriate endpointsTherapyChemotherapyComorbiditiesPatientsTransplantNeoplasmsLeukemiaPopulationDecitabineA First-in-Human, Phase 1, Dose Escalation Study of Sgr-2921 As Monotherapy in Subjects with Relapsed/Refractory Acute Myeloid Leukemia or Myelodysplastic Syndrome
DiNardo C, Strickland S, Skikne B, Zeidan A, Traer E, Carraway H, Frankel S, Weiss D, Wang J, Pirie-Shepherd S, Piccotti J, Wright D, Akinsanya K. A First-in-Human, Phase 1, Dose Escalation Study of Sgr-2921 As Monotherapy in Subjects with Relapsed/Refractory Acute Myeloid Leukemia or Myelodysplastic Syndrome. Blood 2023, 142: 1548. DOI: 10.1182/blood-2023-186036.Peer-Reviewed Original ResearchR AMLAcute myeloid leukemiaRefractory acute myeloid leukemiaCell line-derived xenograftsDose-escalation studyMyelodysplastic syndromeCentral nervous systemDose levelsEscalation studyFirst doseTreatment armsMyeloid leukemiaEastern Cooperative Oncology Group performance statusRelapsed/Refractory Acute Myeloid LeukemiaPatient-derived xenograft AML modelHigh-risk myelodysplastic syndromeHigh unmet medical needAnimal models representativeMultiple prior linesPhase 2 doseSingle-patient cohortsTreatment arm ATreatment arm B.Antitumor activitySingle-dose pharmacokineticsIntensive Induction Chemotherapy Vs Hypomethylating Agents + Venetoclax (HMA/VEN) in NPM1-Mutant Newly Diagnosed Acute Myeloid Leukemia (AML) - a Multicenter Cohort Study
Bewersdorf J, Shimony S, Shallis R, Liu Y, Schaefer E, Zeidan A, Goldberg A, Stein E, Marcucci G, Lindsley R, Chen E, Ramos J, Stein A, DeAngelo D, Neuberg D, Stone R, Ball B, Stahl M. Intensive Induction Chemotherapy Vs Hypomethylating Agents + Venetoclax (HMA/VEN) in NPM1-Mutant Newly Diagnosed Acute Myeloid Leukemia (AML) - a Multicenter Cohort Study. Blood 2023, 142: 2964. DOI: 10.1182/blood-2023-174285.Peer-Reviewed Original ResearchNPM1 mutant acute myeloid leukemiaIntensive induction chemotherapyAcute myeloid leukemiaComposite complete responseMedian overall survivalOverall survivalComplete responseAllo-SCTPt ageAbnormal cytogeneticsCohort studyMyelodysplastic syndromePolymerase chain reactionClinical trialsMyeloid leukemiaNPM1 mutationsLarge multicenter retrospective cohort studyTime-varying covariatesMulticenter retrospective cohort studyAllogeneic stem cell transplantationPrior myelodysplastic syndromeMulticenter cohort studyRetrospective cohort studyStem cell transplantationPrior chemotherapy exposureClinical Outcomes in Patients With Refractory Anemia With Excess Blasts (RAEB) Who Receive Hypomethylating Agents (HMAs)
Zeidan A, Mearns E, Ng C, Shah A, Lamarre N, Yellow-Duke A, Alrawashdh N, Yang B, Cheng W, Bui C, Svensson A. Clinical Outcomes in Patients With Refractory Anemia With Excess Blasts (RAEB) Who Receive Hypomethylating Agents (HMAs). Clinical Lymphoma Myeloma & Leukemia 2023, 24: 177-186. PMID: 37996264, DOI: 10.1016/j.clml.2023.10.010.Peer-Reviewed Original ResearchEvent-free survivalAcute myeloid leukemiaMedian overall survivalOverall survivalHypomethylating agentExcess blastsRefractory anemiaReal-world settingMedian event-free survivalFirst-line therapyHematopoietic cell transplantationEligible patientsClinical outcomesCancer RegistryCell transplantationClinical benefitMedicare databaseClinical effectivenessAML progressionClinical trialsPatient outcomesMyeloid leukemiaPatientsOverall populationSignificant differencesWhen to use which molecular prognostic scoring system in the management of patients with MDS?
Kewan T, Bewersdorf J, Gurnari C, Xie Z, Stahl M, Zeidan A. When to use which molecular prognostic scoring system in the management of patients with MDS? Best Practice & Research Clinical Haematology 2023, 36: 101517. PMID: 38092484, DOI: 10.1016/j.beha.2023.101517.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsInternational Prognostic Scoring SystemPrognostic scoring systemAcute myeloid leukemiaScoring systemRisk stratificationRecurrent molecular alterationsHigh-risk patientsAppropriate risk stratificationManagement of patientsRecurrent genetic mutationsIntensive therapyMyeloid leukemiaTreatment strategiesPrognostic toolDisease pathogenesisMolecular alterationsHematopoietic cancersClinical decisionHeterogeneous groupGenetic mutationsNext-generation sequencingPrognostic systemPatientsVariable propensitySubsequent revisionManagement of Acute Myeloid Leukemia with Myelodysplasia-Related Changes and Therapy-Related Acute Myeloid Leukemia
Bewersdorf J, Zeidan A. Management of Acute Myeloid Leukemia with Myelodysplasia-Related Changes and Therapy-Related Acute Myeloid Leukemia. 2023, 119-128. DOI: 10.1007/978-981-99-3810-0_8.ChaptersTherapy-related AMLAcute myeloid leukemiaSecondary AMLAML-MRCMyeloid leukemiaRandomized phase III clinical trialsPhase III clinical trialsAdverse cytogenetic featuresOverall survival benefitDe novo AMLT-AML patientsYears of ageHigh-risk mutationsInduction chemotherapyMonosomal karyotypeCPX-351Intensive chemotherapyNovo AMLSurvival benefitTreatment landscapeAdverse prognosisFrontline treatmentSubgroup analysisClinical trialsConventional chemotherapySpliceosome mutations are associated with clinical response in a phase 1b/2 study of the PLK1 inhibitor onvansertib in combination with decitabine in relapsed or refractory acute myeloid leukemia
Croucher P, Ridinger M, Becker P, Lin T, Silberman S, Wang E, Zeidan A. Spliceosome mutations are associated with clinical response in a phase 1b/2 study of the PLK1 inhibitor onvansertib in combination with decitabine in relapsed or refractory acute myeloid leukemia. Annals Of Hematology 2023, 102: 3049-3059. PMID: 37702821, PMCID: PMC10567832, DOI: 10.1007/s00277-023-05442-9.Peer-Reviewed Original ResearchAcute myeloid leukemiaR AML patientsAML patientsMyeloid leukemiaRefractory (R/R) AMLRelapsed/refractory (R/R) AMLHigher CR/CRi ratesCR/CRi rateRefractory acute myeloid leukemiaGene signaturePhase 1b/2 studyPhase 1b/2 trialPhase 1b trialBone marrow blastsSF mutationsBone marrow samplesCRi rateComplete remissionMarrow blastsClinical responseCount recoveryInitial safetyMarrow samplesPotential therapyMolecular predictorsTargeting apoptosis dysregulation in myeloid malignancies - The promise of a therapeutic revolution
Santinelli E, Pascale M, Xie Z, Badar T, Stahl M, Bewersdorf J, Gurnari C, Zeidan A. Targeting apoptosis dysregulation in myeloid malignancies - The promise of a therapeutic revolution. Blood Reviews 2023, 62: 101130. PMID: 37679263, DOI: 10.1016/j.blre.2023.101130.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsAcute myeloid leukemiaMyeloid malignanciesLeukemia cell survivalBcl-2 signalingPro-apoptotic agentsClinical studiesMyeloid leukemiaMyeloid neoplasmsTherapeutic revolutionMolecular alterationsMyeloid neoplasiaTherapeutic landscapeSpecific drugsApoptosis dysregulationSynergistic efficacyNew drugsMechanism of apoptosisDrugsMalignancyCombination strategiesCell survivalAttractive targetApoptotic pathwayTreatmentApoptosisStandardising acute myeloid leukaemia classification systems: a perspective from a panel of international experts
Shallis R, Daver N, Altman J, Komrokji R, Pollyea D, Badar T, Bewersdorf J, Bhatt V, de Botton S, de la Fuente Burguera A, Carraway H, Desai P, Dillon R, Duployez N, El Chaer F, Fathi A, Freeman S, Gojo I, Grunwald M, Jonas B, Konopleva M, Lin T, Mannis G, Mascarenhas J, Michaelis L, Mims A, Montesinos P, Pozdnyakova O, Pratz K, Schuh A, Sekeres M, Smith C, Stahl M, Subklewe M, Uy G, Voso M, Walter R, Wang E, Zeidner J, Žučenka A, Zeidan A. Standardising acute myeloid leukaemia classification systems: a perspective from a panel of international experts. The Lancet Haematology 2023, 10: e767-e776. PMID: 37572683, DOI: 10.1016/s2352-3026(23)00159-x.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsAcute myeloid leukemiaMyeloid leukemiaClinical trial eligibilityInternational consensus classificationHeath care providersHealth care providersTrial eligibilityClassification systemResponse assessmentDisease definitionConsensus classificationPatientsDrug developmentLeukemiaConsistent management strategiesInternational expertsRegulatory pathwaysProvidersHematopathologistsCliniciansDiagnosisRacial and Socioeconomic Disparities in Long-Term Outcomes in ≥1 Year Allogeneic Hematopoietic Cell Transplantation Survivors: A CIBMTR Analysis
Blue B, Brazauskas R, Chen K, Patel J, Zeidan A, Steinberg A, Ballen K, Kwok J, Rotz S, Perez M, Kelkar A, Ganguly S, Wingard J, Lad D, Sharma A, Badawy S, Lazarus H, Hashem H, Szwajcer D, Knight J, Bhatt N, Page K, Beattie S, Arai Y, Liu H, Arnold S, Freytes C, Abid M, Beitinjaneh A, Farhadfar N, Wirk B, Winestone L, Agrawal V, Preussler J, Seo S, Hashmi S, Lehmann L, Wood W, Rangarajan H, Saber W, Majhail N. Racial and Socioeconomic Disparities in Long-Term Outcomes in ≥1 Year Allogeneic Hematopoietic Cell Transplantation Survivors: A CIBMTR Analysis. Transplantation And Cellular Therapy 2023, 29: 709.e1-709.e11. PMID: 37482244, PMCID: PMC11258715, DOI: 10.1016/j.jtct.2023.07.013.Peer-Reviewed Original ResearchConceptsHematopoietic cell transplantationLong-term outcomesAllogeneic hematopoietic cell transplantationRace/ethnicityNonrelapse mortalityOverall survivalNon-Hispanic blacksNon-Hispanic whitesSocioeconomic statusMyeloid leukemiaNeighborhood poverty levelFirst allogeneic hematopoietic cell transplantationZip codesAdult allogeneic HCT recipientsMarrow Transplant Research databaseHematopoietic cell transplantation (HCT) survivorsAllogeneic hematopoietic cell transplantation survivorsAllogeneic HCT survivorsAllogeneic HCT recipientsHigh-poverty areasLong-term survivorsStandardized mortality ratioAcute lymphocytic leukemiaAcute myeloid leukemiaChronic myeloid leukemiaOral 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 StatementsConceptsAcute 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 malignanciesOlder patients with chronic myeloid leukemia face suboptimal molecular testing and tyrosine kinase inhibitor adherence
Shallis R, Wang R, Zeidan A, Huntington S, Neparidze N, Stempel J, Mendez L, Di M, Ma X, Podoltsev N. Older patients with chronic myeloid leukemia face suboptimal molecular testing and tyrosine kinase inhibitor adherence. Blood Advances 2023, 7: 3213-3224. PMID: 36939371, PMCID: PMC10338212, DOI: 10.1182/bloodadvances.2022009074.Peer-Reviewed Original ResearchConceptsChronic myeloid leukemiaTKI adherenceTKI initiationOlder patientsMyeloid leukemiaEnd Results-Medicare databaseTyrosine kinase inhibitor usePolymerase chain reaction testingQuantitative polymerase chain reaction testingOlder patient populationCare of patientsHealth care accessReal-world studyReal-world evidenceLow socioeconomic statusLow-income subsidyFirst yearInfluenza vaccinationInhibitor useWorse survivalTKI treatmentMultivariable analysisPatient populationOptimal monitoringCare accessPhase 1/2 Study of the Pan-PIM Kinase Inhibitor INCB053914 Alone or in Combination With Standard-of-Care Agents in Patients With Advanced Hematologic Malignancies
Patel M, Donnellan W, Byrne M, Asch A, Zeidan A, Baer M, Fathi A, Kuykendall A, Zheng F, Walker C, Cheng L, Marando C, Savona M. Phase 1/2 Study of the Pan-PIM Kinase Inhibitor INCB053914 Alone or in Combination With Standard-of-Care Agents in Patients With Advanced Hematologic Malignancies. Clinical Lymphoma Myeloma & Leukemia 2023, 23: 674-686. PMID: 37290996, DOI: 10.1016/j.clml.2023.05.002.Peer-Reviewed Original ResearchConceptsTreatment-emergent adverse eventsDose-limiting toxicityAdvanced hematologic malignanciesAcute myeloid leukemiaMyelodysplastic syndromeHematologic malignanciesCare agentsHigh-risk myelodysplastic syndromeMDS/myeloproliferative neoplasmPhase 1/2 studyEffective combination strategiesAdverse eventsComplete responseLymphoproliferative neoplasmsWeek 12Multiple myelomaSpleen volumeAcute leukemiaMyeloid leukemiaPreclinical modelsPatientsMyeloproliferative neoplasmsMoloney murine leukemia virus (PIM) kinasesMyelofibrosisKinase inhibitors