2023
Why 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
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
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 ResearchConceptsHigh-risk myelodysplastic syndromeRisk myelodysplastic syndromesAcute myeloid leukemiaMyelodysplastic syndromePrognostic implicationsMyeloid leukemiaTP53 alterationsPatientsSyndromeTherapyLeukemiaPhase 1 study of anti-CD47 monoclonal antibody CC-90002 in patients with relapsed/refractory acute myeloid leukemia and high-risk myelodysplastic syndromes
Zeidan AM, DeAngelo DJ, Palmer J, Seet CS, Tallman MS, Wei X, Raymon H, Sriraman P, Kopytek S, Bewersdorf JP, Burgess MR, Hege K, Stock W. Phase 1 study of anti-CD47 monoclonal antibody CC-90002 in patients with relapsed/refractory acute myeloid leukemia and high-risk myelodysplastic syndromes. Annals Of Hematology 2022, 101: 557-569. PMID: 34981142, PMCID: PMC9414073, DOI: 10.1007/s00277-021-04734-2.Peer-Reviewed Original ResearchConceptsAnti-drug antibodiesAcute myeloid leukemiaDose-limiting toxicityRefractory acute myeloid leukemiaHigh-risk myelodysplastic syndromeMyelodysplastic syndromeMyeloid leukemiaCommon treatment-emergent adverse eventsTreatment-emergent adverse eventsADA-positive patientsPhase 2 dosePresence/frequencyUnexpected safety findingsPhase 1 studyAnti-CD47 antibodyCD47-SIRPα interactionMacrophage-mediated killingHematological cancer cell linesFebrile neutropeniaMonotherapy activityCancer cell linesPrimary endpointSecondary endpointsAdverse eventsObjective response
2021
Immune and Epigenetic Landscape of TP53-mutated Acute Myeloid Leukemia (AML) and Higher-Risk Myelodysplastic Syndromes (HR-MDS)
Zeidan A, Bewersdorf J, Hasle V, Thompson E, de Menezes D, Rose S, Boss I, Fox B. Immune and Epigenetic Landscape of TP53-mutated Acute Myeloid Leukemia (AML) and Higher-Risk Myelodysplastic Syndromes (HR-MDS). Blood 2021, 138: 3371. DOI: 10.1182/blood-2021-146329.Peer-Reviewed Original ResearchHigh-risk myelodysplastic syndromeClinical Trials CommitteeAcute myeloid leukemiaBristol-Myers SquibbCurrent equity holderPoor-risk cytogeneticsVariant allele frequencyAML ptsOverall response rateTrials CommitteeMedian OSTP53 mutationsMyeloid neoplasmsFlow cytometryPeripheral bloodT cell genesHigh expressionBone marrowAverage variant allele frequencyRandomized phase 2 studyBone marrow flow cytometryT-cell gene signatureTumor cellsBM blast percentageIPSS-R scoreVenetoclax-based combinations in AML and high-risk MDS prior to and following allogeneic hematopoietic cell transplant
Bewersdorf JP, Derkach A, Gowda L, Menghrajani K, DeWolf S, Ruiz JD, Ponce DM, Shaffer BC, Tamari R, Young JW, Jakubowski AA, Gyurkocza B, Chan A, Xiao W, Glass J, King AC, Cai SF, Daniyan A, Famulare C, Cuello BM, Podoltsev NA, Roshal M, Giralt S, Perales MA, Seropian S, Cho C, Zeidan AM, Prebet T, Stein EM, Tallman MS, Goldberg AD, Stahl M. Venetoclax-based combinations in AML and high-risk MDS prior to and following allogeneic hematopoietic cell transplant. Leukemia & Lymphoma 2021, 62: 3394-3401. PMID: 34477024, PMCID: PMC9012492, DOI: 10.1080/10428194.2021.1966788.Peer-Reviewed Original ResearchConceptsAcute myeloid leukemiaAllogeneic hematopoietic cell transplantAllo-HCTHematopoietic cell transplantSalvage therapyMyelodysplastic syndromeCell transplantMemorial Sloan-Kettering Cancer CenterHigh-risk myelodysplastic syndromeSecond allo-HCTSalvage treatment optionOverall response rateMedian followMedian OSVenetoclax therapyRetrospective studyCancer CenterTreatment optionsOS estimatesMyeloid leukemiaPatientsResponse rateTherapyTransplantMonthsManagement 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 ResearchConceptsImmune 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 MeetingFollowing in the footsteps of acute myeloid leukemia: are we witnessing the start of a therapeutic revolution for higher-risk myelodysplastic syndromes?
Bewersdorf JP, Zeidan AM. Following in the footsteps of acute myeloid leukemia: are we witnessing the start of a therapeutic revolution for higher-risk myelodysplastic syndromes? Leukemia & Lymphoma 2020, 61: 2295-2312. PMID: 32421403, PMCID: PMC7670856, DOI: 10.1080/10428194.2020.1761968.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsHigh-risk myelodysplastic syndromeAcute myeloid leukemiaMyelodysplastic syndromeMyeloid leukemiaAllogeneic hematopoietic stem cell transplantationGenetic testingHematopoietic stem cell transplantationImmune checkpoint inhibitorsCurative treatment optionMainstay of therapyRecent therapeutic advancesStem cell transplantationCurrent treatment approachesAgent azacitidineCheckpoint inhibitorsMost patientsMDS patientsAvailable therapiesCell transplantationPatient subgroupsTreatment optionsTherapeutic advancesIDH inhibitorsIndividualized treatmentNew agentsEmerging 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
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