2024
Combination therapy with hypomethylating agents and venetoclax versus intensive induction chemotherapy in IDH1‐ or IDH2‐mutant newly diagnosed acute myeloid leukemia—A multicenter cohort study
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, Ramos J, Stein A, Pullarkat V, Aldoss I, DeAngelo D, Neuberg D, Stone R, Garciaz S, Ball B, Stahl M. Combination therapy with hypomethylating agents and venetoclax versus intensive induction chemotherapy in IDH1‐ or IDH2‐mutant newly diagnosed acute myeloid leukemia—A multicenter cohort study. American Journal Of Hematology 2024, 99: 1640-1643. PMID: 38751104, DOI: 10.1002/ajh.27366.Peer-Reviewed Original Research
2023
Novel Approaches and Future Directions in Myelodysplastic Syndrome Treatment
Bewersdorf J, Xie Z, Zeidan A. Novel Approaches and Future Directions in Myelodysplastic Syndrome Treatment. The Cancer Journal 2023, 29: 195-202. PMID: 37195776, DOI: 10.1097/ppo.0000000000000658.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsHigh-risk MDS patientsInternational Prognostic Scoring SystemPhase III clinical trialsErythropoiesis-stimulating agentsPrognostic scoring systemRisk stratification toolAdvanced clinical testingStandard of careAcute myeloid leukemiaTelomerase inhibitor imetelstatEncouraging early resultsMyelodysplastic Syndromes TreatmentAnemic patientsAgent monotherapyMDS patientsStratification toolSyndrome treatmentCombination therapyDysplastic changesClinical trialsMyeloid leukemiaTreatment decisionsClonal disorderTreatment selectionClinical testing
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 inhibitorsVenetoclaxTherapyInvestigational venetoclax combination therapy in acute myeloid leukemia – a systematic review and meta-analysis
Shimony S, Rozental A, Bewersdorf J, Goldberg A, Stein E, Grimshaw A, Stone R, DeAngelo D, Wolach O, Stahl M. Investigational venetoclax combination therapy in acute myeloid leukemia – a systematic review and meta-analysis. Haematologica 2022, 107: 2955-2960. PMID: 36453519, PMCID: PMC9713559, DOI: 10.3324/haematol.2022.281453.Peer-Reviewed Original ResearchGilteritinib clinical activity in relapsed/refractory FLT3 mutated acute myeloid leukemia previously treated with FLT3 inhibitors
Numan Y, Rahman Z, Grenet J, Boisclair S, Bewersdorf JP, Collins C, Barth D, Fraga M, Bixby DL, Zeidan AM, Yilmaz M, Desai P, Mannis G, Deutsch YE, Abaza Y, Dinner S, Frankfurt O, Litzow M, Al‐Kali A, Foran JM, Sproat LZ, Jovanovic B, Daver N, Perl AE, Altman JK. Gilteritinib clinical activity in relapsed/refractory FLT3 mutated acute myeloid leukemia previously treated with FLT3 inhibitors. American Journal Of Hematology 2022, 97: 322-328. PMID: 34981560, DOI: 10.1002/ajh.26447.Peer-Reviewed Original ResearchConceptsAcute myeloid leukemiaMyeloid leukemiaRelapsed/Refractory Acute Myeloid LeukemiaComposite complete remission rateRefractory acute myeloid leukemiaLower median overall survivalComplete remission rateMedian overall survivalStem cell transplantCRC ratesLower CRCRefractory FLT3Median survivalRemission rateIntensive inductionOverall survivalCell transplantCombination therapyFLT3 inhibitorsFLT3 mutationsClinical activityUS CentersRetrospective analysisADMIRAL studyMitogen-activated protein kinase pathway
2021
The development and clinical use of oral hypomethylating agents in acute myeloid leukemia and myelodysplastic syndromes: dawn of the total oral therapy era
Schiffer M, Zhao J, Johnson A, Lee J, Bewersdorf JP, Zeidan AM. The development and clinical use of oral hypomethylating agents in acute myeloid leukemia and myelodysplastic syndromes: dawn of the total oral therapy era. Expert Review Of Anticancer Therapy 2021, 21: 989-1002. PMID: 33853476, DOI: 10.1080/14737140.2021.1918002.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsChronic myelomonocytic leukemiaAcute myeloid leukemiaMyelodysplastic syndromeMyeloid leukemiaMyelomonocytic leukemiaHypomethylating agentAllogeneic hematopoietic cell transplantPost-transplant maintenance therapyAcute myeloid leukemia (AML) treatmentHematopoietic cell transplantHigh-risk MDSMyeloid leukemia treatmentPotential combination therapyCC-486Induction chemotherapyOral azacitidineTherapy eraMaintenance therapyOral agentsAdult patientsCell transplantClinical benefitMaintenance treatmentCombination therapyPredictive biomarkersVenetoclax for the treatment of elderly or chemotherapy-ineligible patients with acute myeloid leukemia: a step in the right direction or a game changer?
Agarwal S, Kowalski A, Schiffer M, Zhao J, Bewersdorf JP, Zeidan AM. Venetoclax for the treatment of elderly or chemotherapy-ineligible patients with acute myeloid leukemia: a step in the right direction or a game changer? Expert Review Of Hematology 2021, 14: 199-210. PMID: 33459064, DOI: 10.1080/17474086.2021.1876559.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsAcute myeloid leukemiaIntensive chemotherapyAML patientsTherapeutic optionsMyeloid leukemiaComposite complete remission rateOral BCL-2 inhibitorChemotherapy-ineligible patientsNovel triplet combinationLow-dose cytarabineComplete remission rateDurability of responseAttractive therapeutic optionPubMed/MEDLINERemission rateElderly patientsTreatment landscapeAML treatmentPoor prognosisAggressive malignancyCombination therapyBcl-2 inhibitorsMechanisms of resistanceClinical dataToxicity profile
2020
Randomized trials with checkpoint inhibitors in acute myeloid leukaemia and myelodysplastic syndromes: What have we learned so far and where are we heading?
Bewersdorf JP, Zeidan AM. Randomized trials with checkpoint inhibitors in acute myeloid leukaemia and myelodysplastic syndromes: What have we learned so far and where are we heading? Best Practice & Research Clinical Haematology 2020, 33: 101222. PMID: 33279182, DOI: 10.1016/j.beha.2020.101222.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsAcute myeloid leukemiaRandomized clinical trialsMyelodysplastic syndromeClinical trialsCheckpoint inhibitorsMyeloid leukemiaRecent randomized clinical trialsRecent clinical trial dataEarly phase clinical trialsImmune checkpoint inhibitorsMultiple novel agentsClinical trial dataPhase clinical trialsClinical trial designSynergistic combination therapyImmunophenotypic biomarkersRandomized trialsCombination therapySolid malignanciesNovel agentsTrial designTrial dataNovel targetAvailable evidenceTrialsGilteritinib Remains Clinically Active in Relapsed/Refractory FLT3 Mutated AML Previously Treated with FLT3 inhibitors
Numan Y, Rahman Z, Grenet J, Boisclair S, Bewersdorf J, Barth D, Zeidan A, Yilmaz M, Dinner S, Deutsch Y, Frankfurt O, Litzow M, Al-Kali A, Foran J, Sproat L, Jovanovic B, Daver N, Perl A, Altman J. Gilteritinib Remains Clinically Active in Relapsed/Refractory FLT3 Mutated AML Previously Treated with FLT3 inhibitors. Blood 2020, 136: 5-7. DOI: 10.1182/blood-2020-137251.Peer-Reviewed Original ResearchStem cell transplantMedian survivalFLT3 mutationsBristol-Myers SquibbDaiichi SankyoBoehringer IngelheimCRC ratesLymphoma SocietyCombination therapyPolymerase chain reactionFLT3-ITDSingle agentDrug resistanceAdvisory CommitteeBone marrow flow cytometryComposite complete remissionFLT3-D835 mutationsHigher CRCS ratesNon-transplanted patientsPoor median survivalKaplan-Meier curvesMulti-institutional analysisLog-rank testBayer HealthCare PharmaceuticalsMAPK pathwayNovel and combination therapies for polycythemia vera and essential thrombocythemia: the dawn of a new era
Bewersdorf JP, Zeidan AM. Novel and combination therapies for polycythemia vera and essential thrombocythemia: the dawn of a new era. Expert Review Of Hematology 2020, 13: 1189-1199. PMID: 33076714, PMCID: PMC7722191, DOI: 10.1080/17474086.2020.1839887.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsMeSH KeywordsBone MarrowClinical Trials as TopicCombined Modality TherapyDNA MethylationDrugs, InvestigationalForecastingHistone CodeHumansHydroxyureaInflammationInterferon-alphaJanus Kinase 2Molecular Diagnostic TechniquesMolecular Targeted TherapyMutation, MissenseNitrilesPolycythemia VeraPyrazolesPyrimidinesSignal TransductionTherapies, InvestigationalThrombocythemia, EssentialThrombophiliaThrombosisTumor MicroenvironmentConceptsEssential thrombocythemiaPolycythemia veraNovel agentsPV patientsTreatment selectionHigh-risk essential thrombocythemiaAberrant immune regulationFirst-line treatmentDisease-modifying potentialRecent clinical trialsNegative myeloproliferative neoplasmsBone marrow microenvironmentImmune pathobiologyCombination therapyClinical trialsClinical studiesImmune regulationPV pathogenesisConference abstractsBCR-ABL1Individualized approachMolecular testingClonal proliferationMyeloproliferative neoplasmsPatientsImmune 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 targetPatientsMalignancyTherapyBiomarkersEmerging treatment options for patients with high-risk myelodysplastic syndrome
Bewersdorf JP, Carraway H, Prebet T. Emerging treatment options for patients with high-risk myelodysplastic syndrome. Therapeutic Advances In Hematology 2020, 11: 2040620720955006. PMID: 33240476, PMCID: PMC7675905, DOI: 10.1177/2040620720955006.Peer-Reviewed Original ResearchAcute myeloid leukemiaMyelodysplastic syndromeHigh-risk myelodysplastic syndromeClonal hematopoietic stem cell disordersDriver mutationsCombinations of HMAsImmune checkpoint inhibitorsMinority of patientsModest survival benefitPeripheral blood cytopeniasTargetable driver mutationsHematopoietic stem cell disordersStem cell disordersDysplastic cell morphologyUnited States FoodAgent azacitidineCheckpoint inhibitorsIntensive chemotherapyOral agentsBlood cytopeniasSurvival benefitMDS patientsCombination therapyMDS treatmentTreatment options
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 cellsInhibitorsOne plus one does not always equal two, especially with regard to hypomethylating agents: the question of synergy of azacitidine and lenalidomide for treatment of relapsed acute myeloid leukemia and myelodysplastic syndromes post allogeneic hematopoietic stem cell transplant
Bewersdorf JP, Stahl M, Zeidan AM. One plus one does not always equal two, especially with regard to hypomethylating agents: the question of synergy of azacitidine and lenalidomide for treatment of relapsed acute myeloid leukemia and myelodysplastic syndromes post allogeneic hematopoietic stem cell transplant. Expert Review Of Hematology 2019, 12: 575-578. PMID: 31225770, DOI: 10.1080/17474086.2019.1635005.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsMeSH KeywordsAntigens, CDAzacitidineCD8-Positive T-LymphocytesClinical Trials as TopicDrug Therapy, CombinationFemaleHematopoietic Stem Cell TransplantationHumansLenalidomideLeukemia, Myeloid, AcuteLymphocyte Activation Gene 3 ProteinMaleMiddle AgedMyelodysplastic SyndromesProgrammed Cell Death 1 ReceptorRecurrenceTransplantation, HomologousConceptsAcute myeloid leukemiaHematopoietic stem cell transplantStem cell transplantMyelodysplastic syndromeMyeloid leukemiaAllo-HSCTCell transplantAllogeneic hematopoietic stem cell transplantResponse rateAllogeneic stem cell transplantationNovel salvage therapiesPhase Ib studyStem cell transplantationOverall response rateCycles of treatmentCases of graftHigh response rateMechanism of actionCombination lenalidomideSalvage therapyHost diseaseMost patientsCurative treatmentCombination therapyDisease stageEpigenetic therapy combinations in acute myeloid leukemia: what are the options?
Bewersdorf JP, Shallis R, Stahl M, Zeidan AM. Epigenetic therapy combinations in acute myeloid leukemia: what are the options? Therapeutic Advances In Hematology 2019, 10: 2040620718816698. PMID: 30719265, PMCID: PMC6348528, DOI: 10.1177/2040620718816698.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsAcute myeloid leukemiaCombination therapyTherapy combinationsMyeloid leukemiaEpigenetic therapyAdvanced clinical testingTherapeutic optionsClinical trialsConventional chemotherapyClinical dataPreclinical studiesAML pathogenesisClinical practiceSingle agentClinical testingTherapyLeukemic pathogenesisDriver mutationsDNA methylationHistone methylation inhibitorPathogenesisLeukemiaDehydrogenase inhibitorEpigenetic alterationsActual DNA sequence