2024
Data-driven, harmonised classification system for myelodysplastic syndromes: a consensus paper from the International Consortium for Myelodysplastic Syndromes
Komrokji R, Lanino L, Ball S, Bewersdorf J, Marchetti M, Maggioni G, Travaglino E, Al Ali N, Fenaux P, Platzbecker U, Santini V, Diez-Campelo M, Singh A, Jain A, Aguirre L, Tinsley-Vance S, Schwabkey Z, Chan O, Xie Z, Brunner A, Kuykendall A, Bennett J, Buckstein R, Bejar R, Carraway H, DeZern A, Griffiths E, Halene S, Hasserjian R, Lancet J, List A, Loghavi S, Odenike O, Padron E, Patnaik M, Roboz G, Stahl M, Sekeres M, Steensma D, Savona M, Taylor J, Xu M, Sweet K, Sallman D, Nimer S, Hourigan C, Wei A, Sauta E, D’Amico S, Asti G, Castellani G, Delleani M, Campagna A, Borate U, Sanz G, Efficace F, Gore S, Kim T, Daver N, Garcia-Manero G, Rozman M, Orfao A, Wang A, Foucar M, Germing U, Haferlach T, Scheinberg P, Miyazaki Y, Iastrebner M, Kulasekararaj A, Cluzeau T, Kordasti S, van de Loosdrecht A, Ades L, Zeidan A, Della Porta M, Syndromes I. Data-driven, harmonised classification system for myelodysplastic syndromes: a consensus paper from the International Consortium for Myelodysplastic Syndromes. The Lancet Haematology 2024, 11: e862-e872. PMID: 39393368, DOI: 10.1016/s2352-3026(24)00251-5.Peer-Reviewed Original ResearchGenomic featuresData-driven approachTP53 inactivationGenomic heterogeneityEntity labelsGenetic featuresDel(7q)/-7Myelodysplastic syndromeGenomic profilingData scientistsMutated SF3B1Cluster assignmentComplex karyotypeRUNX1 mutationsModified Delphi consensus processDel(5qIsolated del(5qAcute myeloid leukemiaData-drivenDelphi consensus processMarrow blastsMDS-167 Multilineage and Safety Results From the COMMANDS Trial in Transfusion-Dependent (TD), Erythropoiesis-Stimulating Agent (ESA)-Naive Patients With Very Low-, Low-, or Intermediate-Risk Myelodysplastic Syndromes (MDS)
Garcia-Manero G, Della Porta M, Santini V, Zeidan A, Komrokji R, Li J, Pilot R, Kreitz S, Pozharskaya V, Keeperman K, Lai Y, Valcarcel D, Fenaux P, Platzbecker U. MDS-167 Multilineage and Safety Results From the COMMANDS Trial in Transfusion-Dependent (TD), Erythropoiesis-Stimulating Agent (ESA)-Naive Patients With Very Low-, Low-, or Intermediate-Risk Myelodysplastic Syndromes (MDS). Clinical Lymphoma Myeloma & Leukemia 2024, 24: s388. DOI: 10.1016/s2152-2650(24)01347-8.Peer-Reviewed Original ResearchEA-treated patientsHematological improvement-erythroidAbsolute neutrophil countTransfusion-dependentLR-MDSMyelodysplastic syndromeRBC transfusionBaseline medianPlatelet lineageIntermediate-risk myelodysplastic syndromesESA-naiveBone marrow blastsLowered riskMarrow blastsPlatelet transfusionsRinged sideroblastsPlatelet countNeutrophil countLuspaterceptSafety resultsEpoetin alfaHI-NTreatment periodTransfusionPatientsMDS-166 Clinical Benefit of Luspatercept Treatment in Transfusion-Dependent (TD), Erythropoiesis-Stimulating Agent (ESA)-Naive Patients With Very Low-, Low-, or Intermediate-Risk Myelodysplastic Syndromes (MDS) in the COMMANDS Trial
Zeidan A, Platzbecker U, Della Porta M, Santini V, Garcia-Manero G, Li J, Kreitz S, Pozharskaya V, Rose S, Lai Y, Davidárcel D, Fenaux P, Shortt J, Komrokji R. MDS-166 Clinical Benefit of Luspatercept Treatment in Transfusion-Dependent (TD), Erythropoiesis-Stimulating Agent (ESA)-Naive Patients With Very Low-, Low-, or Intermediate-Risk Myelodysplastic Syndromes (MDS) in the COMMANDS Trial. Clinical Lymphoma Myeloma & Leukemia 2024, 24: s387-s388. DOI: 10.1016/s2152-2650(24)01346-6.Peer-Reviewed Original ResearchEA patientsTransfusion-dependentRBC unitsLuspatercept treatmentRBC-TITransfusion burdenMyelodysplastic syndromeLR-MDSRBC transfusionIntermediate-risk myelodysplastic syndromesEA-treated patientsRBC transfusion independenceBone marrow blastsLowered riskTransfusion independenceMarrow blastsTreatment initiationCumulative medianLuspaterceptEpoetin alfaESA-naivePatients adultsEffective treatmentPatientsInterquartile rangeClinical benefit of luspatercept treatment (tx) in transfusion-dependent (TD), erythropoiesis-stimulating agent (ESA)–naive patients (pts) with very low-, low- or intermediate-risk myelodysplastic syndromes (MDS) in the COMMANDS trial.
Zeidan A, Platzbecker U, Della Porta M, Santini V, Garcia-Manero G, Li J, Kreitz S, Pozharskaya V, Rose S, Lai Y, Valcárcel D, Fenaux P, Shortt J, Komrokji R. Clinical benefit of luspatercept treatment (tx) in transfusion-dependent (TD), erythropoiesis-stimulating agent (ESA)–naive patients (pts) with very low-, low- or intermediate-risk myelodysplastic syndromes (MDS) in the COMMANDS trial. Journal Of Clinical Oncology 2024, 42: 6565-6565. DOI: 10.1200/jco.2024.42.16_suppl.6565.Peer-Reviewed Original ResearchRed blood cell unitsLower-risk MDSRBC-TITransfusion burdenRed blood cellsTransfusion-dependentMyelodysplastic syndromeClinical benefitRed blood cell transfusion independenceAssessment of clinical benefitIntermediate-risk myelodysplastic syndromesLower-risk myelodysplastic syndromesBone marrow blastsClinically meaningful responseYears of ageLuspatercept treatmentMarrow blastsTransfusion independenceMean HbRinged sideroblastsEligible ptsMean hemoglobinHb levelsCumulative medianLuspaterceptDifferentiation 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 3
2023
Validation of the Composite Complete Response (cCR) Definitions in the International Working Group (IWG) 2023 Criteria in Patients (Pts) with Higher-Risk Myelodysplastic Syndromes/Neoplasms (HR-MDS) Treated with Hypomethylating Agents (HMA) - a Large, Multicenter, Retrospective Analysis from the Validate Database
Bewersdorf J, Kewan T, Blaha O, Stahl M, Al Ali N, DeZern A, Sekeres M, Uy G, Carraway H, Desai P, Griffiths E, Stein E, Brunner A, McMahon C, Zeidner J, Savona M, Stempel J, Chandhok N, Logothetis C, Roboz G, Rolles B, Wang E, Harris A, Amaya M, Hawkins H, Grenet J, Shallis R, Xie Z, Maciejewski J, Sallman D, Della Porta M, Komrokji R, Zeidan A. Validation of the Composite Complete Response (cCR) Definitions in the International Working Group (IWG) 2023 Criteria in Patients (Pts) with Higher-Risk Myelodysplastic Syndromes/Neoplasms (HR-MDS) Treated with Hypomethylating Agents (HMA) - a Large, Multicenter, Retrospective Analysis from the Validate Database. Blood 2023, 142: 324. DOI: 10.1182/blood-2023-180299.Peer-Reviewed Original ResearchImproved OSHypomethylating agentHMA initiationMedian OSResponse assessmentTP53 mutationsResponse definitionsPartial hematologic recoveryPredictors of OSMultivariable Cox modelBone marrow blastsKaplan-Meier analysisLog-rank testOverall response rateEfficacy of therapyMultivariable regression modelsReal-world analysisAllo-HCTBM assessmentBM evaluationHemoglobin thresholdHematologic recoveryMarrow blastsMedian durationMedian ageData-Driven Harmonization of 2022 Who and ICC Classifications of Myelodysplastic Syndromes/Neoplasms (MDS): A Study By the International Consortium for MDS (icMDS)
Lanino L, Ball S, Bewersdorf J, Marchetti M, Maggioni G, Travaglino E, Al Ali N, Fenaux P, Platzbecker U, Santini V, Diez-Campelo M, Singh A, Jain A, Aguirre L, Tinsley-Vance S, Schwabkey Z, Chan O, Xie Z, Brunner A, Kuykendall A, Bennett J, Buckstein R, Bejar R, Carraway H, DeZern A, Griffiths E, Halene S, Hasserjian R, Lancet J, List A, Loghavi S, Odenike O, Padron E, Patnaik M, Roboz G, Stahl M, Sekeres M, Steensma D, Savona M, Taylor J, Xu M, Sweet K, Sallman D, Nimer S, Hourigan C, Wei A, Sauta E, D'Amico S, Asti G, Castellani G, Borate U, Sanz G, Efficace F, Gore S, Kim T, Daver N, Garcia-Manero G, Rozman M, Orfao A, Wang S, Foucar M, Germing U, Haferlach T, Scheinberg P, Miyazaki Y, Iastrebner M, Kulasekararaj A, Cluzeau T, Kordasti S, van de Loosdrecht A, Ades L, Zeidan A, Komrokji R, Della Porta M. Data-Driven Harmonization of 2022 Who and ICC Classifications of Myelodysplastic Syndromes/Neoplasms (MDS): A Study By the International Consortium for MDS (icMDS). Blood 2023, 142: 998. DOI: 10.1182/blood-2023-186580.Peer-Reviewed Original ResearchBlast countMost patientsTP53 mutationsTET2 mutationsChromosomal abnormalitiesMore TP53 mutationsBone marrow blastsGene mutationsSF3B1 mutationsClinical decision-making processHigh-risk mutationsMarrow blastsMultilineage dysplasiaPatient characteristicsAML patientsClinical entityInternational cohortSHAP analysisMDS casesPatientsClinical relevanceCytogenetic abnormalitiesClinical settingComplex karyotypeU2AF1 mutationsCombining Gene Mutation with Transcriptomic Data Improves Outcome Prediction in Myelodysplastic Syndromes
Sauta E, Zampini M, Dall'Olio D, Sala C, Todisco G, Travaglino E, Lanino L, Tentori C, Maggioni G, D'Amico S, Asti G, Dall'Olio L, Mosca E, Ubezio M, Campagna A, Riva E, Bicchieri M, Savevski V, Santoro A, Kordasti S, Santini V, Diez-Campelo M, Kubasch A, Platzbecker U, Fenaux P, Zhao L, Zeidan A, Haferlach T, Castellani G, Della Porta M. Combining Gene Mutation with Transcriptomic Data Improves Outcome Prediction in Myelodysplastic Syndromes. Blood 2023, 142: 1863. DOI: 10.1182/blood-2023-186222.Peer-Reviewed Original ResearchAcute myeloid leukemiaProportional hazards modelOverall survivalClinical outcomesMyelodysplastic syndromeClinical featuresMDS patientsPrognostic informationConcordance indexCox proportional hazards modelConventional prognostic scoresIPSS-R scorePrimary end pointBone marrow blastsHarrell's concordance indexPeripheral blood cytopeniasPrognostic scoring systemRisk of progressionAdditional prognostic informationCytogenetic alterationsGene mutationsIndividual patient levelSame clinical phenotypeBlood cytopeniasMarrow blastsSpliceosome mutations are associated with clinical response in a phase 1b/2 study of the PLK1 inhibitor onvansertib in combination with decitabine in relapsed or refractory acute myeloid leukemia
Croucher P, Ridinger M, Becker P, Lin T, Silberman S, Wang E, Zeidan A. Spliceosome mutations are associated with clinical response in a phase 1b/2 study of the PLK1 inhibitor onvansertib in combination with decitabine in relapsed or refractory acute myeloid leukemia. Annals Of Hematology 2023, 102: 3049-3059. PMID: 37702821, PMCID: PMC10567832, DOI: 10.1007/s00277-023-05442-9.Peer-Reviewed Original ResearchAcute myeloid leukemiaR AML patientsAML patientsMyeloid leukemiaRefractory (R/R) AMLRelapsed/refractory (R/R) AMLHigher CR/CRi ratesCR/CRi rateRefractory acute myeloid leukemiaGene signaturePhase 1b/2 studyPhase 1b/2 trialPhase 1b trialBone marrow blastsSF mutationsBone marrow samplesCRi rateComplete remissionMarrow blastsClinical responseCount recoveryInitial safetyMarrow samplesPotential therapyMolecular predictors
2021
Evaluating Complete Remission with Incomplete Hematologic Recovery (CRh) As a Response Criterion in Myelodysplastic Syndromes (MDS)
Brunner A, Gavralidis A, Al Ali N, Komrokji R, Zeidan A, Sallman D. Evaluating Complete Remission with Incomplete Hematologic Recovery (CRh) As a Response Criterion in Myelodysplastic Syndromes (MDS). Blood 2021, 138: 1522. DOI: 10.1182/blood-2021-151815.Peer-Reviewed Original ResearchClinical Trials CommitteeStable diseaseComplete remissionHMA therapyBone marrow blastsHematologic improvementProgressive diseaseMyelodysplastic syndromePartial remissionTrials CommitteeResponse criteriaMarrow blastsOverall survivalSpeakers bureauHigh-risk myelodysplastic syndromeAdvisory CommitteeIncomplete hematologic recoveryIWG 2006 criteriaMethod of KaplanRisk myelodysplastic syndromesOngoing prospective studyMoffitt Cancer CenterBest overall responsePrediction of OSMassachusetts General Hospital
2020
A Phase Ib Study of Onvansertib, a Novel Oral PLK1 Inhibitor, in Combination Therapy for Patients with Relapsed or Refractory Acute Myeloid Leukemia
Zeidan AM, Ridinger M, Lin TL, Becker PS, Schiller GJ, Patel PA, Spira AI, Tsai ML, Samuëlsz E, Silberman SL, Erlander M, Wang ES. A Phase Ib Study of Onvansertib, a Novel Oral PLK1 Inhibitor, in Combination Therapy for Patients with Relapsed or Refractory Acute Myeloid Leukemia. Clinical Cancer Research 2020, 26: 6132-6140. PMID: 32998961, DOI: 10.1158/1078-0432.ccr-20-2586.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAntineoplastic Combined Chemotherapy ProtocolsCytarabineDecitabineDrug Resistance, NeoplasmFemaleFollow-Up StudiesHumansLeukemia, Myeloid, AcuteMaleMaximum Tolerated DoseMiddle AgedNeoplasm Recurrence, LocalPiperazinesPrognosisPyrazolesQuinazolinesSalvage TherapyConceptsAcute myeloid leukemiaPhase Ib studyMyeloid leukemiaIb studyRefractory (R/R) AMLFirst-cycle dose-limiting toxicitiesRefractory acute myeloid leukemiaOngoing phase II trialAntileukemic activityMost grade 3Low-dose cytarabinePhase II trialBone marrow blastsDose-limiting toxicityPLK1 inhibitorsPolo-like kinase 1Evaluable patientsExploratory endpointsComplete remissionII trialPrimary endpointAdverse eventsClinical responseMarrow blastsCount recovery
2019
A Phase 1b Study Evaluating the Safety and Efficacy of Venetoclax As Monotherapy or in Combination with Azacitidine for the Treatment of Relapsed/Refractory Myelodysplastic Syndrome
Zeidan A, Pollyea D, Garcia J, Brunner A, Roncolato F, Borate U, Odenike O, Bajel A, Watson A, Götze K, Nolte F, Tan P, Hong W, Dunbar M, Zhou Y, Gressick L, Ainsworth W, Harb J, Salem A, Hayslip J, Swords R, Garcia-Manero G. A Phase 1b Study Evaluating the Safety and Efficacy of Venetoclax As Monotherapy or in Combination with Azacitidine for the Treatment of Relapsed/Refractory Myelodysplastic Syndrome. Blood 2019, 134: 565. DOI: 10.1182/blood-2019-124994.Peer-Reviewed Original ResearchStock/stock optionsTreatment-emergent adverse eventsProgression-free survivalMedian progression-free survivalAbbVie IncOverall survivalFebrile neutropeniaStable diseaseMarrow blastsMyelodysplastic syndromeBcl-2 inhibitorsAstra ZenecaFrequent treatment-emergent adverse eventsInternational Working Group 2006 criteriaSerious treatment-emergent adverse eventsAllogeneic stem cell transplantationAdvisory CommitteeDaiichi SankyoCycles of AZACycles of decitabineECOG performance statusPhase 1b studyPhase 2 dosePredominant grade 3Refractory myelodysplastic syndrome
2018
Hypomethylating agents in relapsed and refractory AML: outcomes and their predictors in a large international patient cohort
Stahl M, DeVeaux M, Montesinos P, Itzykson R, Ritchie EK, Sekeres MA, Barnard JD, Podoltsev NA, Brunner AM, Komrokji RS, Bhatt VR, Al-Kali A, Cluzeau T, Santini V, Fathi AT, Roboz GJ, Fenaux P, Litzow MR, Perreault S, Kim TK, Prebet T, Vey N, Verma V, Germing U, Bergua JM, Serrano J, Gore SD, Zeidan AM. Hypomethylating agents in relapsed and refractory AML: outcomes and their predictors in a large international patient cohort. Blood Advances 2018, 2: 923-932. PMID: 29685952, PMCID: PMC5916007, DOI: 10.1182/bloodadvances.2018016121.Peer-Reviewed Original ResearchConceptsOverall survivalRR-AMLMedian OSOlder acute myeloid leukemia patientsAcute myeloid leukemia patientsCR/CRiIncomplete count recoveryMedian overall survivalDecreased overall survivalBone marrow blastsReasonable therapeutic optionMyeloid leukemia patientsPredictors of responseImproved response ratesLarge international patient cohortInternational patient cohortGood responseComplete remissionHematologic improvementRefractory AMLMarrow blastsMedian ageCount recoveryFrontline treatmentTherapeutic options
2015
Differential Response to Hypomethylating Agents Based on Sex: A Report on Behalf of the MDS Clinical Research Consortium (MDS CRC)
DeZern A, Zeidan A, Barnard J, Hand W, Al Ali N, Brown F, Zimmerman C, Roboz G, Komrokji R, Garcia-Manero G, Steensma D, Sekeres M. Differential Response to Hypomethylating Agents Based on Sex: A Report on Behalf of the MDS Clinical Research Consortium (MDS CRC). Blood 2015, 126: 2889. DOI: 10.1182/blood.v126.23.2889.2889.Peer-Reviewed Original ResearchHigh-risk myelodysplastic syndromeMedian overall survivalBone marrow blastsFirst-line therapyOverall survivalTime of presentationMyelodysplastic syndromeMedian OSBlast percentageBetter OSMarrow blastsCytogenetic categoriesBone marrow blast percentageMDS Clinical Research ConsortiumStandard first-line therapyInternational Working Group criteriaCox PH analysisCox proportional analysisMarrow blast percentageSpeakers bureauClinical Research ConsortiumLog-rank testDate of deathFuture prospective investigationsMann-Whitney U test