2024
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)
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 ResearchMeSH KeywordsAntineoplastic Combined Chemotherapy ProtocolsBridged Bicyclo Compounds, HeterocyclicHumansLeukemia, Myeloid, AcuteSulfonamidesTumor Suppressor Protein p53
2023
A multicenter phase Ib trial of the histone deacetylase inhibitor entinostat in combination with pembrolizumab in patients with myelodysplastic syndromes/neoplasms or acute myeloid leukemia refractory to hypomethylating agents
Bewersdorf J, Shallis R, Sharon E, Park S, Ramaswamy R, Roe C, Irish J, Caldwell A, Wei W, Yacoub A, Madanat Y, Zeidner J, Altman J, Odenike O, Yerrabothala S, Kovacsovics T, Podoltsev N, Halene S, Little R, Piekarz R, Gore S, Kim T, Zeidan A. A multicenter phase Ib trial of the histone deacetylase inhibitor entinostat in combination with pembrolizumab in patients with myelodysplastic syndromes/neoplasms or acute myeloid leukemia refractory to hypomethylating agents. Annals Of Hematology 2023, 103: 105-116. PMID: 38036712, DOI: 10.1007/s00277-023-05552-4.Peer-Reviewed Original ResearchMeSH KeywordsAntineoplastic Combined Chemotherapy ProtocolsHistone Deacetylase InhibitorsHumansLeukemia, Myeloid, AcuteMyelodysplastic SyndromesConceptsDose-limiting toxicityAcute myeloid leukemiaMarrow complete remissionPhase Ib trialAdverse eventsIb trialDose escalationNCI Cancer Therapy Evaluation ProgramAcute myeloid leukemia refractoryHematologic adverse eventsProtocol-defined responseDose level 1Anti-PD1 therapyAnti-PD1 antibodyDose-escalation designLimited clinical efficacySystems immunology approachHistone deacetylase inhibitor entinostatLeukemia refractoryMCR patientsComplete remissionRespiratory failureSuppressor cellsEscalation designClinical efficacyMoving toward disease modification in polycythemia vera
Bewersdorf J, How J, Masarova L, Bose P, Pemmaraju N, Mascarenhas J, Rampal R. Moving toward disease modification in polycythemia vera. Blood 2023, 142: 1859-1870. PMID: 37729609, DOI: 10.1182/blood.2023021503.Peer-Reviewed Original ResearchMeSH KeywordsHumansHydroxyureaInterferon-alphaJanus Kinase 2Leukemia, Myeloid, AcutePolycythemia VeraPrimary MyelofibrosisThrombocytosisThrombosisConceptsAcute myeloid leukemiaProgression to myelofibrosisPolycythemia veraCytoreductive therapyBCR-ABL1-negative myeloproliferative neoplasmsLow-risk PVLow-risk diseaseHistory of thrombosisHigh-risk diseaseDisease-modifying treatment modalitiesAssociated with higher ratesEvolving treatment landscapeClinically meaningful outcome measuresDisease-related symptomsInterferon alfaMyeloproliferative neoplasmsThromboembolic eventsPatient ageMyeloid leukemiaTreatment modalitiesIFN-a2bTherapeutic phlebotomyActivating mutationsVasomotor symptomsDisease courseWhen 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 StatementsMeSH KeywordsClinical Decision-MakingHumansLeukemia, Myeloid, AcuteMutationMyelodysplastic SyndromesPrognosisConceptsInternational 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 revisionTargeting 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 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 pathwaysProvidersHematopathologistsCliniciansDiagnosisEvolution of Therapeutic Benefit Measurement Criteria in Myelodysplastic Syndromes/Neoplasms
Stempel J, Xie Z, Bewersdorf J, Stahl M, Zeidan A. Evolution of Therapeutic Benefit Measurement Criteria in Myelodysplastic Syndromes/Neoplasms. The Cancer Journal 2023, 29: 203-211. PMID: 37195777, DOI: 10.1097/ppo.0000000000000666.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsInternational Working Group response criteriaResponse criteriaPhase III clinical trialsIWG 2006 criteriaRisk of progressionPatient-focused outcomesClonal myeloid neoplasmsAcute myeloid leukemiaTherapeutic response assessmentPatient-centered responsesNovel drug developmentHematologic recoveryProgressive cytopeniasClinical trialsIWG criteriaLong-term benefitsMyeloid leukemiaIneffective hematopoiesisMyeloid neoplasmsResponse assessmentDisease severityNovel 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 testingCost-Effectiveness Analyses in AML: What Have We Learned, How Should This Impact Patient Care, and What Needs to Be Done in the Future?
Bewersdorf J, Huntington S, Zeidan A. Cost-Effectiveness Analyses in AML: What Have We Learned, How Should This Impact Patient Care, and What Needs to Be Done in the Future? Journal Of The National Comprehensive Cancer Network 2023, 21: 522-528. PMID: 37037494, DOI: 10.6004/jnccn.2023.70012.Peer-Reviewed Original ResearchMeSH KeywordsAdultCost-Benefit AnalysisCost-Effectiveness AnalysisHumansLeukemia, Myeloid, AcutePatient CareUnited StatesConceptsCost-effectiveness analysisEconomic modeling techniquesCost-effectiveness studiesFinite financial resourcesDrug pricesHealth policy decisionsPolicy decisionsFinancial resourcesResource allocationUnited StatesPublic interestCostHealthcare systemPricesSuch analysesLimited resourcesAllocationCountriesConsumersData sourcesPayersAssumptionBenefitsBudgetary considerationsDifferent interventionsSurvival of TP53-mutated acute myeloid leukemia patients receiving allogeneic stem cell transplantation after first induction or salvage therapy: results from the Consortium on Myeloid Malignancies and Neoplastic Diseases (COMMAND)
Badar T, Atallah E, Shallis R, Saliba A, Patel A, Bewersdorf J, Grenet J, Stahl M, Duvall A, Burkart M, Palmisiano N, Bradshaw D, Kubiak M, Dinner S, Goldberg A, Abaza Y, Murthy G, Kota V, Litzow M. Survival of TP53-mutated acute myeloid leukemia patients receiving allogeneic stem cell transplantation after first induction or salvage therapy: results from the Consortium on Myeloid Malignancies and Neoplastic Diseases (COMMAND). Leukemia 2023, 37: 799-806. PMID: 36807649, DOI: 10.1038/s41375-023-01847-7.Peer-Reviewed Original ResearchConceptsEvent-free survivalAllo-HSCTOverall survivalChronic GVHDAllogeneic hematopoietic stem cell transplantAllogeneic stem cell transplantationMedian event-free survivalHematopoietic stem cell transplantAcute myeloid leukemia patientsMedian overall survivalPost allo-HSCTReduced intensity conditioningStem cell transplantStem cell transplantationLong-term outcomesMyeloid leukemia patientsMulti-center studyAcute graftComplete remissionHost diseaseSalvage therapyComplex cytogeneticsMyeloablative conditioningMedian ageCell transplant
2022
Disparities in receiving disease‐directed therapy, allogeneic stem cell transplantation in non‐Hispanic Black patients with TP53‐mutated acute myeloid leukemia
Badar T, Litzow M, Shallis R, Patel A, Saliba A, Burkart M, Bewersdorf J, Stahl M, De Camargo Correia G, Murthy S, Abaza Y, Duvall A, Bradshaw D, Kota V, Dinner S, Goldberg A, Palmisiano N, Al Kali A, Atallah E. Disparities in receiving disease‐directed therapy, allogeneic stem cell transplantation in non‐Hispanic Black patients with TP53‐mutated acute myeloid leukemia. Cancer 2022, 129: 934-945. PMID: 36545710, DOI: 10.1002/cncr.34604.Peer-Reviewed Original ResearchMeSH KeywordsBlack PeopleHealthcare DisparitiesHematopoietic Stem Cell TransplantationHumansLeukemia, Myeloid, AcuteRetrospective StudiesTumor Suppressor Protein p53White PeopleConceptsAcute myeloid leukemiaAllogeneic stem cell transplantationNHB patientsStem cell transplantationNHW patientsCell transplantationMyeloid leukemiaTherapy-related acute myeloid leukemiaNon-Hispanic black patientsCurative-intent therapyLow-intensity chemotherapyBest supportive careComplete response rateMedian patient ageProportion of patientsSubset of patientsDisease-directed therapyHigher proportionIntensive chemotherapyPatient ageSupportive careBlack patientsClinical outcomesTreatment disparitiesRetrospective studyCost-effectiveness of azacitidine and ivosidenib in newly diagnosed older, intensive chemotherapy-ineligible patients with IDH1-mutant acute myeloid leukemia
Bewersdorf J, Patel K, Goshua G, Shallis R, Podoltsev N, Stahl M, Stein E, Huntington S, Zeidan A. Cost-effectiveness of azacitidine and ivosidenib in newly diagnosed older, intensive chemotherapy-ineligible patients with IDH1-mutant acute myeloid leukemia. Leukemia & Lymphoma 2022, 64: 454-461. PMID: 36493798, PMCID: PMC9957935, DOI: 10.1080/10428194.2022.2140288.Peer-Reviewed Original ResearchMeSH KeywordsAzacitidineCost-Benefit AnalysisHumansIsocitrate DehydrogenaseLeukemia, Myeloid, AcutePyridinesQuality-Adjusted Life YearsUnited StatesHitting the brakes on accelerated and blast-phase myeloproliferative neoplasms: current and emerging concepts
Bewersdorf J, Rampal R. Hitting the brakes on accelerated and blast-phase myeloproliferative neoplasms: current and emerging concepts. Hematology 2022, 2022: 218-224. PMID: 36485103, PMCID: PMC9820986, DOI: 10.1182/hematology.2022000341.Peer-Reviewed Original ResearchMeSH KeywordsBlast CrisisHumansLeukemia, Myeloid, AcuteMutationMyeloproliferative DisordersPrognosisConceptsMyeloproliferative neoplasmsBlast-phase MPNBlast-phase myeloproliferative neoplasmsAllogeneic hematopoietic cell transplantationBCR-ABL-negative myeloproliferative neoplasmsStages of clinical developmentMedian overall survivalHigh-risk molecular featuresHematopoietic cell transplantationCurative therapeutic modalityPrognosis of patientsAcute myeloid leukemiaMinority of patientsClinical trial enrollmentMPN-BPMyeloid blastsCurative intentHypomethylating agentsOverall survivalCell transplantationPeripheral bloodMyeloid leukemiaPalliative treatmentBone marrowClinical developmentPrognostic implications of mono-hit and multi-hit TP53 alterations in patients with acute myeloid leukemia and higher risk myelodysplastic syndromes treated with azacitidine-based therapy
Zeidan A, Bewersdorf J, Hasle V, Shallis R, Thompson E, de Menezes D, Rose S, Boss I, Halene S, Haferlach T, Fox B. Prognostic implications of mono-hit and multi-hit TP53 alterations in patients with acute myeloid leukemia and higher risk myelodysplastic syndromes treated with azacitidine-based therapy. Leukemia 2022, 37: 240-243. PMID: 36437356, DOI: 10.1038/s41375-022-01766-z.Peer-Reviewed Original ResearchMeSH KeywordsAntimetabolites, AntineoplasticAzacitidineHumansLeukemia, Myeloid, AcuteMyelodysplastic SyndromesPrognosisTumor Suppressor Protein p53Molecular predictors of immunophenotypic measurable residual disease clearance in acute myeloid leukemia
Stahl M, Derkach A, Farnoud N, Bewersdorf J, Robinson T, Famulare C, Cho C, Devlin S, Menghrajani K, Patel M, Cai S, Miles L, Bowman R, Geyer M, Dunbar A, Epstein‐Peterson Z, McGovern E, Schulman J, Glass J, Taylor J, Viny A, Stein E, Getta B, Arcila M, Gao Q, Barker J, Shaffer B, Papadopoulos E, Gyurkocza B, Perales M, Abdel‐Wahab O, Levine R, Giralt S, Zhang Y, Xiao W, Pai N, Papaemmanuil E, Tallman M, Roshal M, Goldberg A. Molecular predictors of immunophenotypic measurable residual disease clearance in acute myeloid leukemia. American Journal Of Hematology 2022, 98: 79-89. PMID: 36251406, PMCID: PMC10080561, DOI: 10.1002/ajh.26757.Peer-Reviewed Original ResearchMeSH KeywordsHematopoietic Stem Cell TransplantationHumansLeukemia, Myeloid, AcuteNeoplasm, ResidualPrognosisRemission InductionStem Cell TransplantationTransplantation, HomologousConceptsMeasurable residual diseaseAcute myeloid leukemiaAllo-SCTInduction chemotherapyPersistent diseaseMyeloid leukemiaAllogeneic stem cell transplantationStem cell transplantationMonosomy 5Residual diseaseDisease clearanceKaryotypic abnormalitiesPrognostic factorsCell transplantationMolecular predictorsMRD clearanceRemissionClinical trialsNext-generation sequencingChemotherapyPatientsMutation patternsTherapyLeukemiaMRDVenetoclax-based salvage therapy in patients with relapsed/refractory acute myeloid leukemia previously treated with FLT3 or IDH1/2 inhibitors
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. Venetoclax-based salvage therapy in patients with relapsed/refractory acute myeloid leukemia previously treated with FLT3 or IDH1/2 inhibitors. Leukemia & Lymphoma 2022, 64: 188-196. PMID: 36287540, PMCID: PMC9905301, DOI: 10.1080/10428194.2022.2136952.Peer-Reviewed Original ResearchMeSH KeywordsBridged Bicyclo Compounds, HeterocyclicFms-Like Tyrosine Kinase 3HumansIsocitrate DehydrogenaseLeukemia, Myeloid, AcuteRetrospective StudiesSalvage TherapyConceptsAcute myeloid leukemiaSalvage therapyIDH1/2 inhibitorsIDH2 inhibitorsMyeloid leukemiaResponse rateRefractory acute myeloid leukemiaEffective salvage therapyLow-dose cytarabineMedian overall survivalRetrospective cohort studyOverall response rateLow response rateCohort studyOverall survivalAML patientsTreatment optionsFLT3 inhibitorsITD mutationPatientsTherapyFLT3Little dataVenetoclaxInhibitorsFinding consistency in classifications of myeloid neoplasms: a perspective on behalf of the International Workshop for Myelodysplastic Syndromes
Zeidan AM, Bewersdorf JP, Buckstein R, Sekeres MA, Steensma DP, Platzbecker U, Loghavi S, Boultwood J, Bejar R, Bennett JM, Borate U, Brunner AM, Carraway H, Churpek JE, Daver NG, Della Porta M, DeZern AE, Efficace F, Fenaux P, Figueroa ME, Greenberg P, Griffiths EA, Halene S, Hasserjian RP, Hourigan CS, Kim N, Kim TK, Komrokji RS, Kutchroo V, List AF, Little RF, Majeti R, Nazha A, Nimer SD, Odenike O, Padron E, Patnaik MM, Roboz GJ, Sallman DA, Sanz G, Stahl M, Starczynowski DT, Taylor J, Xie Z, Xu M, Savona MR, Wei AH, Abdel-Wahab O, Santini V. Finding consistency in classifications of myeloid neoplasms: a perspective on behalf of the International Workshop for Myelodysplastic Syndromes. Leukemia 2022, 36: 2939-2946. PMID: 36266326, DOI: 10.1038/s41375-022-01724-9.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsEfficacy 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 ResearchAberrant EVI1 splicing contributes to EVI1-rearranged leukemia
Tanaka A, Nakano T, Nomura M, Yamazaki H, Bewersdorf J, Mulet-Lazaro R, Hogg S, Liu B, Penson A, Yokoyama A, Zang W, Havermans M, Koizumi M, Hayashi Y, Cho H, Kanai A, Lee S, Xiao M, Koike Y, Zhang Y, Fukumoto M, Aoyama Y, Konuma T, Kunimoto H, Inaba T, Nakajima H, Honda H, Kawamoto H, Delwel R, Abdel-Wahab O, Inoue D. Aberrant EVI1 splicing contributes to EVI1-rearranged leukemia. Blood 2022, 140: 875-888. PMID: 35709354, PMCID: PMC9412007, DOI: 10.1182/blood.2021015325.Peer-Reviewed Original ResearchConceptsAcute myeloid leukemiaMyeloid leukemiaEVI1 isoformsSF3B1 mutationsAberrant 3' splice sitesSelf-renewal of hematopoietic stem cellsSplicing factor SF3B1Zinc finger domainExonic splicing enhancerIn-frame insertionCryptic branch pointPathogenesis of myeloid leukemiaPatient-derived cell linesHematopoietic stem cellsRNA-splicingSplicing enhancerSplice siteEpigenomic analysesMutant SF3B1Promoter usageExon 13Leukemic transformationSplice variantsGenomic alterationsUpregulated transcripts