2024
Toward a more patient‐centered drug development process in clinical trials for patients with myelodysplastic syndromes/neoplasms (MDS): Practical considerations from the International Consortium for MDS (icMDS)
Efficace F, Buckstein R, Abel G, Giesinger J, Fenaux P, Bewersdorf J, Brunner A, Bejar R, Borate U, DeZern A, Greenberg P, Roboz G, Savona M, Sparano F, Boultwood J, Komrokji R, Sallman D, Xie Z, Sanz G, Carraway H, Taylor J, Nimer S, Della Porta M, Santini V, Stahl M, Platzbecker U, Sekeres M, Zeidan A. Toward a more patient‐centered drug development process in clinical trials for patients with myelodysplastic syndromes/neoplasms (MDS): Practical considerations from the International Consortium for MDS (icMDS). HemaSphere 2024, 8: e69. PMID: 38774655, PMCID: PMC11106800, DOI: 10.1002/hem3.69.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsPatient-reported outcomesPatient-reported outcome dataHealth-related qualityPatient-reported outcome endpointsHealth-related quality of lifeClinical trialsImprove patients' health-related qualityPatients' health-related qualityPatient-reported outcome itemsQuality of lifeTime-to-event analysisRandomized controlled trialsTreatment decision-makingPatient carePatient populationTreatment advancesControlled trialsPatientsIncurable diseaseAssessment strategiesHRQoLBenefit/risk assessmentDrug development processTrialsTherapy
2023
E7820, an Anti-Cancer Sulfonamide, in Combination with Venetoclax in Patients with Splicing Factor Mutant Myeloid Malignancies: A Phase II Clinical Trial
Bewersdorf J, Chandhok N, Watts J, Derkach A, Abdel-Wahab O, Stein E, Taylor J. E7820, an Anti-Cancer Sulfonamide, in Combination with Venetoclax in Patients with Splicing Factor Mutant Myeloid Malignancies: A Phase II Clinical Trial. Blood 2023, 142: 1547. DOI: 10.1182/blood-2023-182369.Peer-Reviewed Original ResearchAcute myeloid leukemiaEastern Cooperative Oncology GroupPhase II clinical trialChronic myelomonocytic leukemiaMyelodysplastic syndromePatient-derived xenograftsII clinical trialsPreclinical dataSplicing factor genesMyeloid malignanciesClinical trialsAdequate end-organ functionContext of combination therapyDay 1Safety run-in phaseRefractory acute myeloid leukemiaSimon 2-stage designResponse rateDynamic BH3 profilingCycles of therapyNegative prognostic impactEvent-free survivalMyelodysplastic syndrome patientsHuman acute myeloid leukemiaPhase II trialIntensive 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 exposureE7820, an anti-cancer sulfonamide, degrades RBM39 in patients with splicing factor mutant myeloid malignancies: a phase II clinical trial
Bewersdorf J, Stahl M, Taylor J, Mi X, Chandhok N, Watts J, Derkach A, Wysocki M, Lu S, Bourcier J, Hogg S, Rahman J, Chaudhry S, Totiger T, Abdel-Wahab O, Stein E. E7820, an anti-cancer sulfonamide, degrades RBM39 in patients with splicing factor mutant myeloid malignancies: a phase II clinical trial. Leukemia 2023, 37: 2512-2516. PMID: 37814121, PMCID: PMC10681888, DOI: 10.1038/s41375-023-02050-4.Peer-Reviewed Original ResearchManagement 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 chemotherapyEvolution 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 testingWhat’s Next after Hypomethylating Agents Failure in Myeloid Neoplasms? A Rational Approach
Awada H, Gurnari C, Xie Z, Bewersdorf J, Zeidan A. What’s Next after Hypomethylating Agents Failure in Myeloid Neoplasms? A Rational Approach. Cancers 2023, 15: 2248. PMID: 37190176, PMCID: PMC10137017, DOI: 10.3390/cancers15082248.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsAcute myeloid leukemiaMDS/AML patientsEarly clinical trialsPotential therapeutic agentAML patientsMultidrug combinationsClinical trialsMyeloid leukemiaMyeloid neoplasmsRational approachSingle agentCurrent managementTherapeutic potentialStandardized guidelinesTherapeutic agentsMutational characteristicsPatientsNeoplasmsLatest findingsGenomic factorsCellular adaptationAgentsHMA resistanceFailureLeukemiaCurrent landscape of translational and clinical research in myelodysplastic syndromes/neoplasms (MDS): Proceedings from the 1st International Workshop on MDS (iwMDS) Of the International Consortium for MDS (icMDS)
Bewersdorf J, Xie Z, Bejar R, Borate U, Boultwood J, Brunner A, Buckstein R, Carraway H, Churpek J, Daver N, Porta M, DeZern A, Fenaux P, Figueroa M, Gore S, Griffiths E, Halene S, Hasserjian R, Hourigan C, Kim T, Komrokji R, Kuchroo V, List A, Loghavi S, Majeti R, Odenike O, Patnaik M, Platzbecker U, Roboz G, Sallman D, Santini V, Sanz G, Sekeres M, Stahl M, Starczynowski D, Steensma D, Taylor J, Abdel-Wahab O, Xu M, Savona M, Wei A, Zeidan A. Current landscape of translational and clinical research in myelodysplastic syndromes/neoplasms (MDS): Proceedings from the 1st International Workshop on MDS (iwMDS) Of the International Consortium for MDS (icMDS). Blood Reviews 2023, 60: 101072. PMID: 36934059, DOI: 10.1016/j.blre.2023.101072.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsImmune checkpoint inhibitorsSpecific molecular alterationsNovel animal modelInnate immune systemCheckpoint inhibitorsImmune dysregulationMDS patientsClinical trialsNovel therapiesTherapeutic strategiesAnimal modelsGermline predispositionImmune systemMolecular alterationsClinical researchInternational ConsortiumNeoplasmsClinical workGenetic landscapeInternational WorkshopPatientsCurrent landscapePathogenesisTherapyDiseaseWhy do we not have more drugs approved for MDS? A critical viewpoint on novel drug development in MDS
Frumm S, Shimony S, Stone R, DeAngelo D, Bewersdorf J, Zeidan A, Stahl M. Why do we not have more drugs approved for MDS? A critical viewpoint on novel drug development in MDS. Blood Reviews 2023, 60: 101056. PMID: 36805300, DOI: 10.1016/j.blre.2023.101056.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsMyelodysplastic syndromeDNA methyltransferase inhibitorLow risk (LR) MDSHigh-risk myelodysplastic syndromeHigh transfusion needsRisk myelodysplastic syndromesCurrent treatment landscapeErythropoiesis-stimulating agentsNovel drug developmentHR-MDSTreatment landscapeTransfusion needsTargetable mutationsClinical trialsMDS pathogenesisNew agentsRing sideroblastsMore drugsUnmet needTherapy developmentDrug developmentMethyltransferase inhibitorFactor mutationsApprovalInflammationConsensus 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 StatementsConceptsHigh-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 agents
2022
A Phase II Clinical Trial of E7820 for Patients with Relapsed/Refractory Myeloid Malignancies with Mutations in Splicing Factor Genes
Bewersdorf J, Stahl M, Taylor J, Chandhok N, Watts J, Derkach A, Wysocki M, Kostantakis V, Lu S, Bourcier J, Hogg S, Totiger T, Abdel-Wahab O, Stein E. A Phase II Clinical Trial of E7820 for Patients with Relapsed/Refractory Myeloid Malignancies with Mutations in Splicing Factor Genes. Blood 2022, 140: 9065-9067. DOI: 10.1182/blood-2022-156830.Peer-Reviewed Original ResearchMolecular 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 ResearchConceptsMeasurable residual diseaseAcute myeloid leukemiaAllo-SCTInduction chemotherapyPersistent diseaseMyeloid leukemiaAllogeneic stem cell transplantationStem cell transplantationMonosomy 5Residual diseaseDisease clearanceKaryotypic abnormalitiesPrognostic factorsCell transplantationMolecular predictorsMRD clearanceRemissionClinical trialsNext-generation sequencingChemotherapyPatientsMutation patternsTherapyLeukemiaMRD
2021
Hypomethylating Agents and FLT3 Inhibitors As Maintenance Treatment for Acute Myeloid Leukemia and Myelodysplastic Syndrome After Allogeneic Hematopoietic Stem Cell Transplantation–A Systematic Review and Meta-Analysis
Bewersdorf JP, Allen C, Mirza AS, Grimshaw AA, Giri S, Podoltsev NA, Gowda L, Cho C, Tallman MS, Zeidan AM, Stahl M. Hypomethylating Agents and FLT3 Inhibitors As Maintenance Treatment for Acute Myeloid Leukemia and Myelodysplastic Syndrome After Allogeneic Hematopoietic Stem Cell Transplantation–A Systematic Review and Meta-Analysis. Transplantation And Cellular Therapy 2021, 27: 997.e1-997.e11. PMID: 34551341, PMCID: PMC9533376, DOI: 10.1016/j.jtct.2021.09.005.Peer-Reviewed Original ResearchConceptsAcute myeloid leukemiaRelapse-free survivalMaintenance therapyMyelodysplastic syndromeFLT3 inhibitorsAllo-HCTHazard ratioMaintenance treatmentClinical trialsMyeloid leukemiaAllogeneic hematopoietic stem cell transplantationControl groupSystematic reviewAllogeneic hematopoietic cell transplantMeasurable residual disease statusHematopoietic stem cell transplantationMeasurable residual disease testingNon-relapse mortalityHematopoietic cell transplantPre-emptive treatmentResidual disease statusStem cell transplantationFavorable safety profileSame patient cohortRandom-effects model
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 evidenceTrialsSafety and Efficacy of Maintenance Treatment Following Allogeneic Hematopoietic Cell Transplant in Acute Myeloid Leukemia and Myelodysplastic Syndrome - a Systematic Review and Meta-Analysis
Bewersdorf J, Tallman M, Cho C, Zeidan A, Stahl M. Safety and Efficacy of Maintenance Treatment Following Allogeneic Hematopoietic Cell Transplant in Acute Myeloid Leukemia and Myelodysplastic Syndrome - a Systematic Review and Meta-Analysis. Blood 2020, 136: 34-35. DOI: 10.1182/blood-2020-136671.Peer-Reviewed Original ResearchAcute myeloid leukemiaRelapse-free survivalAllogeneic hematopoietic cell transplantHematopoietic cell transplantFLT3 inhibitorsMyelodysplastic syndromeAllo-HCTOverall survivalRFS ratesChronic GVHDMaintenance therapyCell transplantPatient selectionClinical trialsMyeloid leukemiaADC therapeuticsSystematic reviewMinimal residual disease testingAdvisory CommitteeDaiichi SankyoHigh-risk geneticsRate of GVHDPre-emptive treatmentCareful patient selectionPrognosis of patientsNovel 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 neoplasmsPatientsInterferon alpha therapy in essential thrombocythemia and polycythemia vera—a systematic review and meta-analysis
Bewersdorf JP, Giri S, Wang R, Podoltsev N, Williams RT, Tallman MS, Rampal RK, Zeidan AM, Stahl M. Interferon alpha therapy in essential thrombocythemia and polycythemia vera—a systematic review and meta-analysis. Leukemia 2020, 35: 1643-1660. PMID: 32868875, PMCID: PMC7917159, DOI: 10.1038/s41375-020-01020-4.Peer-Reviewed Original ResearchConceptsOverall response ratePEG-IFNPolycythemia veraEssential thrombocythemiaHematologic responsePV patientsResponse rateSystematic reviewMeta-regression analysis resultsSafe long-term treatmentPartial hematologic responseSafety of interferonInterferon-alpha therapyLong-term treatmentRandom-effects modelMeta-regression analysisWeb of ScienceTreatment discontinuationCochrane RegistryAdverse eventsComplete responsePartial responsePrimary outcomeThromboembolic complicationsClinical trialsImmune 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
Hypomethylating agent (HMA) therapy use and survival in older adults with Refractory Anemia with Excess Blasts (RAEB) in the United States (USA): a large propensity score-matched population-based study†
Davidoff AJ, Hu X, Bewersdorf JP, Wang R, Podoltsev NA, Huntington SF, Gore SD, Ma X, Zeidan AM. Hypomethylating agent (HMA) therapy use and survival in older adults with Refractory Anemia with Excess Blasts (RAEB) in the United States (USA): a large propensity score-matched population-based study†. Leukemia & Lymphoma 2019, 61: 1178-1187. PMID: 31878809, PMCID: PMC7735409, DOI: 10.1080/10428194.2019.1703970.Peer-Reviewed Original ResearchConceptsHigh-risk myelodysplastic syndromeExcess blastsRefractory anemiaOverall survival benefitRetrospective cohort studyMedian OSOS benefitRAEB patientsCohort studySurvival benefitTherapy useMyelodysplastic syndromeClinical trialsLower riskMedicare dataPatientsPropensity scoreOlder adultsDiagnosisAnemiaQuartileUnited StatesAssociationEnd resultOS