2023
Targeting 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 StatementsMeSH KeywordsAntineoplastic AgentsApoptosisHumansLeukemia, Myeloid, AcuteMyeloproliferative DisordersConceptsAcute 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 pathwayTreatmentApoptosis
2022
Efficacy 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
A review of FLT3 inhibitors in acute myeloid leukemia
Zhao JC, Agarwal S, Ahmad H, Amin K, Bewersdorf JP, Zeidan AM. A review of FLT3 inhibitors in acute myeloid leukemia. Blood Reviews 2021, 52: 100905. PMID: 34774343, PMCID: PMC9846716, DOI: 10.1016/j.blre.2021.100905.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsMeSH KeywordsAntineoplastic AgentsFms-Like Tyrosine Kinase 3HumansLeukemia, Myeloid, AcuteMutationPrognosisProtein Kinase InhibitorsConceptsAcute myeloid leukemiaFLT3 mutationsMyeloid leukemiaTreatment of AMLInhibitor maintenance therapyDrug resistance mechanismsCommon genetic aberrationsConsolidation chemotherapyRefractory FLT3Maintenance therapyPoor prognosisPrognostic implicationsStromal protectionFLT3 inhibitorsStandard inductionADMIRAL studyFLT3Genetic aberrationsLeukemiaResistance mechanismsMutationsMonotherapyChemotherapyPrognosisGilteritinibMaintenance therapies in acute myeloid leukemia: the renaissance of an old therapeutic concept
Bewersdorf J, Tallman M, Stahl M. Maintenance therapies in acute myeloid leukemia: the renaissance of an old therapeutic concept. Current Opinion In Oncology 2021, 33: 658-669. PMID: 34341323, DOI: 10.1097/cco.0000000000000778.Peer-Reviewed Original ResearchConceptsAcute myeloid leukemiaAcute myeloid leukemia patientsMaintenance therapyAllo-HCTOverall survivalIntensive chemotherapyMyeloid leukemiaPersistence of leukemic cellsSafety of maintenance therapyAllogeneic hematopoietic cell transplantationRelapse-free survivalDuration of remissionHematopoietic cell transplantationIndividualized therapeutic approachFLT3 inhibitor sorafenibCC-486Induction chemotherapyOS benefitDisease relapseCell transplantationInhibitor sorafenibImproved survivalPatient selectionTargeted agentsLeukemic cellsManagement of patients with higher-risk myelodysplastic syndromes after failure of hypomethylating agents: What is on the horizon?
Bewersdorf JP, Zeidan AM. Management of patients with higher-risk myelodysplastic syndromes after failure of hypomethylating agents: What is on the horizon? Best Practice & Research Clinical Haematology 2021, 34: 101245. PMID: 33762100, DOI: 10.1016/j.beha.2021.101245.Peer-Reviewed Original ResearchMeSH KeywordsAntineoplastic AgentsAzacitidineDNA MethylationEnzyme InhibitorsHumansMyelodysplastic SyndromesRemission InductionTreatment OutcomeConceptsImmune checkpoint inhibitorsHigh-risk myelodysplastic syndromeHMA failureMyelodysplastic syndromeAgent azacitidineSalvage therapyNovel immune checkpoint inhibitorsEffective salvage therapyBCL-2 inhibitor venetoclaxCommon clinical dilemmaManagement of patientsStandard of careRationale drug developmentCheckpoint inhibitorsFrontline therapyMost patientsComplete responseMDS patientsFrontline settingFrontline treatmentShorter survivalClinical dilemmaInhibitor venetoclaxClinical testingPatients
2020
Management of higher risk myelodysplastic syndromes after hypomethylating agents failure: are we about to exit the black hole?
Bewersdorf JP, Zeidan AM. Management of higher risk myelodysplastic syndromes after hypomethylating agents failure: are we about to exit the black hole? Expert Review Of Hematology 2020, 13: 1131-1142. PMID: 32876498, DOI: 10.1080/17474086.2020.1819233.Peer-Reviewed Original ResearchMeSH KeywordsAntineoplastic AgentsBiomarkersCombined Modality TherapyDisease ManagementDisease SusceptibilityDNA MethylationDrug DevelopmentDrug Resistance, NeoplasmHumansMolecular Targeted TherapyMutationMyelodysplastic SyndromesPrognosisRemission InductionRetreatmentTreatment FailureTreatment OutcomeConceptsHigh-risk myelodysplastic syndromeHMA failureMyelodysplastic syndromeHR-MDS patientsRisk myelodysplastic syndromesMainstay of treatmentImmune pathogenesisMost patientsComplete responseImmune therapyAbysmal prognosisNovel agentsTherapeutic approachesTherapeutic conceptsImmune evasionTreatment approachesPatientsGenetic testingSyndromePathogenesisTreatmentMolecular mechanismsRecent studiesFailureAnnual MeetingImmune checkpoint inhibition in myeloid malignancies: Moving beyond the PD-1/PD-L1 and CTLA-4 pathways
Bewersdorf JP, Shallis RM, Zeidan AM. Immune checkpoint inhibition in myeloid malignancies: Moving beyond the PD-1/PD-L1 and CTLA-4 pathways. Blood Reviews 2020, 45: 100709. PMID: 32487480, DOI: 10.1016/j.blre.2020.100709.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsImmune checkpoint inhibitorsMyeloid malignanciesPD-1/PD-L1CTLA-4 pathwayImmune checkpoint inhibitionAcute myeloid leukemiaSafe combination therapyICI therapyImmunologic landscapeCheckpoint inhibitorsDisease coursePD-L1Checkpoint inhibitionMyelodysplastic syndromeCombination therapyMechanisms of resistanceClinical trialsMyeloid leukemiaClinical developmentPotential biomarkersNovel targetPatientsMalignancyTherapyBiomarkers
2019
Hedgehog pathway inhibition as a therapeutic target in acute myeloid leukemia
Shallis RM, Bewersdorf JP, Boddu PC, Zeidan AM. Hedgehog pathway inhibition as a therapeutic target in acute myeloid leukemia. Expert Review Of Anticancer Therapy 2019, 19: 717-729. PMID: 31422721, DOI: 10.1080/14737140.2019.1652095.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsAcute myeloid leukemiaHh pathway inhibitorsMyeloid leukemiaSurvival of AMLPathway inhibitorHh pathwayPoor-risk diseaseHedgehog pathway inhibitionStem cellsCombination therapyClinical trialsFirst approvalTherapeutic strategiesTherapeutic targetPathway inhibitionHematopoietic stem cellsNeoplasm therapyOlder populationTherapyHedgehog pathwayFurther studiesLeukemiaNormal hematopoiesisAdult stem cellsInhibitorsHealthcare expenses for treatment of acute myeloid leukemia
Bewersdorf JP, Shallis R, Wang R, Huntington S, Perreault S, Ma X, Zeidan AM. Healthcare expenses for treatment of acute myeloid leukemia. Expert Review Of Hematology 2019, 12: 641-650. PMID: 31159602, DOI: 10.1080/17474086.2019.1627869.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsMeSH KeywordsAntineoplastic AgentsCost-Benefit AnalysisHealth Care CostsHematopoietic Stem Cell TransplantationHospitalizationHumansLeukemia, Myeloid, AcuteConceptsHematopoietic stem cell transplantInsurance statusHealthcare costsTreatment approachesAllogeneic hematopoietic stem cell transplantAcute myeloid leukemia (AML) treatmentStem cell transplantTreatment costsDirect healthcare costsInpatient treatment costsPatient insurance statusPersonalized treatment approachesAcute myeloid leukemiaMyeloid leukemia treatmentInfluence health policyIntensive chemotherapyOral therapyCell transplantMain cost driversMyeloid leukemiaNovel agentsMedical outcomesLeukemia treatmentHealthcare resourcesAMLTransforming growth factor (TGF)-β pathway as a therapeutic target in lower risk myelodysplastic syndromes
Bewersdorf JP, Zeidan AM. Transforming growth factor (TGF)-β pathway as a therapeutic target in lower risk myelodysplastic syndromes. Leukemia 2019, 33: 1303-1312. PMID: 30962581, DOI: 10.1038/s41375-019-0448-2.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsMeSH KeywordsAnimalsAntineoplastic AgentsHumansMolecular Targeted TherapyMyelodysplastic SyndromesSignal TransductionTransforming Growth Factor betaConceptsErythropoiesis stimulating agentsMyelodysplastic syndromeGrowth factorIneffective erythropoiesisLower-risk myelodysplastic syndromesTGF-β pathway inhibitorLR-MDS patientsFurther therapeutic optionsRisk myelodysplastic syndromesLimited therapy optionsTGF-β receptor activationPromising therapeutic approachPhysiologic conditionsTGF-β pathwayAberrant TGFImmunomodulator lenalidomideLR-MDSMyelosuppressive effectsTherapeutic optionsTherapy optionsLife impairmentAdditional potential targetsClinical dataMDS pathogenesisTherapeutic approachesAre we witnessing the start of a therapeutic revolution in acute myeloid leukemia?
Bewersdorf JP, Stahl M, Zeidan AM. Are we witnessing the start of a therapeutic revolution in acute myeloid leukemia? Leukemia & Lymphoma 2019, 60: 1354-1369. PMID: 30652518, DOI: 10.1080/10428194.2018.1546854.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsAML patientsPivotal clinical trial dataOverall survival rateAcute myeloid leukemiaClinical trial dataMechanism of actionIntensive chemotherapyRefractory AMLOlder patientsAML treatmentCD33 antibodyPreclinical dataMyeloid leukemiaClinical developmentTherapeutic revolutionUS FoodDrug AdministrationSurvival rateAdvanced stagePatientsFDA approvalTrial dataPromising agentNovel therapeuticsNew drugs