2024
Differentiation syndrome associated with treatment with IDH2 inhibitor enasidenib: pooled analysis from clinical trials
Montesinos P, Fathi A, de Botton S, Stein E, Zeidan A, Zhu Y, Prebet T, Vigil C, Bluemmert I, Yu X, DiNardo C. Differentiation syndrome associated with treatment with IDH2 inhibitor enasidenib: pooled analysis from clinical trials. Blood Advances 2024, 8: 2509-2519. PMID: 38507688, PMCID: PMC11131052, DOI: 10.1182/bloodadvances.2023011914.Peer-Reviewed Original ResearchAcute myeloid leukemiaDevelopment of differentiation syndromeRisk factorsPooled analysisIDH2-mutant acute myeloid leukemiaClinical trialsAcute myeloid leukemia populationMedian time to onsetClinical features of DSBone marrow blastsNon-specific symptomsTime to onsetBaseline risk factorsTreatment of DSSymptoms of DSIdentified risk factorsFeatures of DSMarrow blastsSystemic steroidsPulmonary infiltratesClinical responseMutant IDH2 inhibitorMyeloid leukemiaClinical featuresGrade 3Toward 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 processTrialsTherapyClinical activity, pharmacokinetics, and pharmacodynamics of oral hypomethylating agents for myelodysplastic syndromes/neoplasms and acute myeloid leukemia: A multidisciplinary review
Haumschild R, Kennerly-Shah J, Barbarotta L, Zeidan A. Clinical activity, pharmacokinetics, and pharmacodynamics of oral hypomethylating agents for myelodysplastic syndromes/neoplasms and acute myeloid leukemia: A multidisciplinary review. Journal Of Oncology Pharmacy Practice 2024, 30: 721-736. PMID: 38509812, PMCID: PMC11118786, DOI: 10.1177/10781552241238979.Peer-Reviewed Original ResearchOral hypomethylating agentsAcute myeloid leukemiaHypomethylating agentsPK-PD profilesPharmacokinetic (PK)-pharmacodynamicMyeloid leukemiaTreatment selectionPK-PDConcentration-time curveIntravenous (IVImprove treatment outcomesCC-486IV decitabineOral azacitidineMaintenance therapySubcutaneous azacitidineNo significant differenceImprove quality of lifeAzacitidineClinical trialsClinical activityTreatment outcomesDisease settingsDecitabineDisease outcome
2023
Intensive 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 exposureClinical Outcomes in Patients With Refractory Anemia With Excess Blasts (RAEB) Who Receive Hypomethylating Agents (HMAs)
Zeidan A, Mearns E, Ng C, Shah A, Lamarre N, Yellow-Duke A, Alrawashdh N, Yang B, Cheng W, Bui C, Svensson A. Clinical Outcomes in Patients With Refractory Anemia With Excess Blasts (RAEB) Who Receive Hypomethylating Agents (HMAs). Clinical Lymphoma Myeloma & Leukemia 2023, 24: 177-186. PMID: 37996264, DOI: 10.1016/j.clml.2023.10.010.Peer-Reviewed Original ResearchEvent-free survivalAcute myeloid leukemiaMedian overall survivalOverall survivalHypomethylating agentExcess blastsRefractory anemiaReal-world settingMedian event-free survivalFirst-line therapyHematopoietic cell transplantationEligible patientsClinical outcomesCancer RegistryCell transplantationClinical benefitMedicare databaseClinical effectivenessAML progressionClinical trialsPatient outcomesMyeloid leukemiaPatientsOverall populationSignificant differencesManagement 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 chemotherapyUpdates on risk stratification and management of lower-risk myelodysplastic syndromes/neoplasms
Badar T, Madanat Y, Zeidan A. Updates on risk stratification and management of lower-risk myelodysplastic syndromes/neoplasms. Future Oncology 2023, 19: 1877-1889. PMID: 37750305, DOI: 10.2217/fon-2023-0454.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsErythropoiesis-stimulating agentsTreatment-naive patientsHigh-risk patientsMeaningful efficacyIndolent courseDismal prognosisRandomized trialsRisk stratificationNeoplasm patientsSerial monitoringClinical trialsNovel therapiesPatientsAppropriate managementModest responseGood responseNeoplasmsTrialsNovel compoundsLuspaterceptLenalidomidePrognosisAnemiaTherapyMore needsEpidemiology and Pathogenesis of Myelodysplastic Syndrome
Rotter L, Shimony S, Ling K, Chen E, Shallis R, Zeidan A, Stahl M. Epidemiology and Pathogenesis of Myelodysplastic Syndrome. The Cancer Journal 2023, 29: 111-121. PMID: 37195766, DOI: 10.1097/ppo.0000000000000665.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsMyelodysplastic syndromeClonal hematopoiesisMDS pathophysiologyFrank MDSOutcomes of patientsOngoing clinical trialsAcute myeloid leukemiaIndividualized therapeutic approachesRisk assessment toolVariable cytopeniasOverall incidenceUnderlying pathophysiologyClinical trialsIneffective hematopoiesisMyeloid leukemiaNovel therapiesClonal cytopeniaTherapeutic modalitiesClonal disorderTherapeutic approachesUnique molecular profileEpidemiological assessmentDisease evolutionUnknown significancePathophysiologyEvolution 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 landscapePathogenesisTherapyDiseaseSTIMULUS-MDS2 design and rationale: a phase III trial with the anti-TIM-3 sabatolimab (MBG453) + azacitidine in higher risk MDS and CMML-2
Zeidan A, Giagounidis A, Sekeres M, Xiao Z, Sanz G, Van Hoef M, Ma F, Hertle S, Santini V. STIMULUS-MDS2 design and rationale: a phase III trial with the anti-TIM-3 sabatolimab (MBG453) + azacitidine in higher risk MDS and CMML-2. Future Oncology 2023, 19: 631-642. PMID: 37083373, DOI: 10.2217/fon-2022-1237.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsHigh-risk myelodysplastic syndromeChronic myelomonocytic leukemiaMyelodysplastic syndromeCMML-2Tim-3Hematopoietic stem cell transplantationT-cell immunoglobulin domainMucin domain 3Risk myelodysplastic syndromesPhase III trialsStem cell transplantationLeukemic stem cellsFavorable tolerabilityIII trialsNovel immunotherapiesPoor outcomeCell transplantationLeukemic blastsClinical trialsNovel therapiesMyelomonocytic leukemiaDurable benefitImmune systemMyeloid malignanciesMeaningful improvementsWhy 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 agentsConsiderations for Drug Development in Myelodysplastic Syndromes
Sekeres M, Kim N, DeZern A, Norsworthy K, Garcia J, de Claro R, Theoret M, Jen E, Ehrlich L, Zeidan A, Komrokji R. Considerations for Drug Development in Myelodysplastic Syndromes. Clinical Cancer Research 2023, 29: 2573-2579. PMID: 36688922, PMCID: PMC10349686, DOI: 10.1158/1078-0432.ccr-22-3348.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsMyelodysplastic syndromeTrial designDrug developmentResponse criteriaLow-risk diseaseHigh-risk patientsFuture trial designClinical trial designQuality of lifeValidation of PatientHigh-need populationDurable responsesOverall survivalAnemic patientsTransfusion dependencyClinical benefitPatient populationAdvanced ageClinical trialsDose reductionOutcome instrumentsNew therapiesPreclinical modelingPatientsActive drugAdvances in myelodysplastic syndromes: promising novel agents and combination strategies
Madanat Y, Xie Z, Zeidan A. Advances in myelodysplastic syndromes: promising novel agents and combination strategies. Expert Review Of Hematology 2023, 16: 51-63. PMID: 36620919, DOI: 10.1080/17474086.2023.2166923.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsHigh-risk myelodysplastic syndromeMultiple novel agentsMyelodysplastic syndromeNovel agentsClinical trialsTreatment optionsPhase III clinical trialsSelect clinical trialsLow-risk diseaseClonal hematopoietic stem cell neoplasmHigh-risk diseaseBest treatment optionHematopoietic stem cell neoplasmsInnate immune systemStem cell neoplasmMechanism of actionHMA therapyEarly safetyTreatment paradigmEfficacy dataCell neoplasmsDrug combinationsClinical developmentUnmet needImmune system
2022
TP53‐altered acute myeloid leukemia and myelodysplastic syndrome with excess blasts should be approached as a single entity
Shallis R, Daver N, Altman J, Hasserjian R, Kantarjian H, Platzbecker U, Santini V, Wei A, Sallman D, Zeidan A. TP53‐altered acute myeloid leukemia and myelodysplastic syndrome with excess blasts should be approached as a single entity. Cancer 2022, 129: 175-180. PMID: 36397669, DOI: 10.1002/cncr.34535.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsEvaluating complete remission with partial hematologic recovery (CRh) as a response criterion in myelodysplastic syndromes (MDS)
Brunner A, Gavralidis A, Ali N, Hunter A, Komrokji R, Zeidan A, Sallman D. Evaluating complete remission with partial hematologic recovery (CRh) as a response criterion in myelodysplastic syndromes (MDS). Blood Cancer Journal 2022, 12: 153. PMID: 36379923, PMCID: PMC9666661, DOI: 10.1038/s41408-022-00748-9.Peer-Reviewed Original ResearchConceptsPartial hematologic recoveryMyelodysplastic syndromeHematologic recoveryResponse criteriaCR/CRhIWG 2006 criteriaDuration of therapyBest overall responseTime of therapyCR responseCRH responseDNMTi therapyOS associationComplete remissionMedian OSOverall survivalAdult patientsAllogeneic transplantsMedian ageMDS patientsMultivariable analysisClinical trialsSimilar survivalPatientsTherapyCHIPing away the progression potential of CHIP: A new reality in the making
Xie Z, Zeidan AM. CHIPing away the progression potential of CHIP: A new reality in the making. Blood Reviews 2022, 58: 101001. PMID: 35989137, DOI: 10.1016/j.blre.2022.101001.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsClonal hematopoiesisEffective preventive strategiesEvidence-based recommendationsClinical sequelaeInterventional trialsClinical outcomesClinical trialsPreventive strategiesInterventional strategiesProgression potentialClinical implicationsIndeterminate potentialTrialsMolecular mechanismsLatest updatesHematopoiesisUrgent need