2023
The ELEMENT-MDS Trial: A Phase 3 Randomized Study Evaluating Luspatercept Versus Epoetin Alfa in Erythropoiesis-Stimulating Agent-Naive, Non-Transfusion-Dependent, Lower-Risk Myelodysplastic Syndromes
Zeidan A, Komrokji R, Buckstein R, Santini V, Rose S, Malini P, Lew G, Aggarwal D, Keeperman K, Jiang H, Giuseppi A, Zhang J, Cluzeau T, Shortt J, Platzbecker U. The ELEMENT-MDS Trial: A Phase 3 Randomized Study Evaluating Luspatercept Versus Epoetin Alfa in Erythropoiesis-Stimulating Agent-Naive, Non-Transfusion-Dependent, Lower-Risk Myelodysplastic Syndromes. Blood 2023, 142: 6503. DOI: 10.1182/blood-2023-178635.Peer-Reviewed Original ResearchRBC transfusion dependenceErythropoiesis-stimulating agentsLR-MDSEpoetin alfaMyelodysplastic syndromeTransfusion dependenceSecondary endpointsStarting doseOverall survivalTransfusion independenceWeek 1Baseline serum erythropoietin levelsIntermediate-risk myelodysplastic syndromesIPSS-R risk categoryLower-risk myelodysplastic syndromesRed blood cell transfusionHigh-risk myelodysplastic syndromeInternational Prognostic Scoring SystemAdditional secondary endpointsRBC transfusion independenceTransfusion-free survivalKey secondary endpointBlood cell transfusionPatient Global ImpressionPhase 3 studyDurable Continuous Transfusion Independence (TI) with Imetelstat in IMerge Phase 3 for Patients with Heavily Transfused Non-Del(5q) Lower-Risk Myelodysplastic Syndromes (LR-MDS) Relapsed/Refractory (R/R) to or Ineligible for Erythropoiesis-Stimulating Agents (ESAs)
Platzbecker U, Komrokji R, Zeidan A, Fenaux P, Sekeres M, Savona M, Madanat Y, Jonášová A, Illmer T, Sherman L, Berry T, Riggs J, Xia Q, Navada S, Wan Y, Huang F, Feller F, Santini V. Durable Continuous Transfusion Independence (TI) with Imetelstat in IMerge Phase 3 for Patients with Heavily Transfused Non-Del(5q) Lower-Risk Myelodysplastic Syndromes (LR-MDS) Relapsed/Refractory (R/R) to or Ineligible for Erythropoiesis-Stimulating Agents (ESAs). Blood 2023, 142: 4605. DOI: 10.1182/blood-2023-181154.Peer-Reviewed Original ResearchLower-risk myelodysplastic syndromesErythropoiesis stimulating agentsPhase 3 trialTransfusion independenceVariant allele frequencyEnd pointTransfusion burdenAdverse eventsRed blood cell transfusionExploratory end pointsFrequent adverse eventsPrimary end pointRBC transfusion burdenReversible grade 3Secondary end pointsBlood cell transfusionDisease-modifying activityKaplan-Meier methodDuration of responseLoss of responseAdditional baseline characteristicsHigh telomerase activityCell transfusionBaseline characteristicsClinical responseImpact of Genomic Landscape and Mutational Burden on Primary Endpoint Responses in the COMMANDS Study
Komrokji R, Guerrero M, Garcia-Manero G, Zeidan A, Platzbecker U, Hayati S, Vodala S. Impact of Genomic Landscape and Mutational Burden on Primary Endpoint Responses in the COMMANDS Study. Blood 2023, 142: 4591. DOI: 10.1182/blood-2023-178689.Peer-Reviewed Original ResearchErythropoiesis-stimulating agentsSuperior clinical benefitLR-MDSClinical benefitSimilar response ratesResponse rateRisk groupsMutational burdenGene mutationsRing sideroblastsRed blood cell transfusionInternational Prognostic Scoring SystemShorter leukemia-free survivalBaseline erythropoietin levelsComparable clinical benefitFavorable clinical benefitBlood cell transfusionLeukemia-free survivalProgression-free survivalSimilar clinical benefitsPrimary endpoint analysisPrognostic scoring systemBone marrow samplesSignificant differencesDriver gene mutationsEfficacy and safety of luspatercept versus epoetin alfa in erythropoiesis-stimulating agent-naive, transfusion-dependent, lower-risk myelodysplastic syndromes (COMMANDS): interim analysis of a phase 3, open-label, randomised controlled trial
Platzbecker U, Della Porta M, Santini V, Zeidan A, Komrokji R, Shortt J, Valcarcel D, Jonasova A, Dimicoli-Salazar S, Tiong I, Lin C, Li J, Zhang J, Giuseppi A, Kreitz S, Pozharskaya V, Keeperman K, Rose S, Shetty J, Hayati S, Vodala S, Prebet T, Degulys A, Paolini S, Cluzeau T, Fenaux P, Garcia-Manero G. Efficacy and safety of luspatercept versus epoetin alfa in erythropoiesis-stimulating agent-naive, transfusion-dependent, lower-risk myelodysplastic syndromes (COMMANDS): interim analysis of a phase 3, open-label, randomised controlled trial. The Lancet 2023, 402: 373-385. PMID: 37311468, DOI: 10.1016/s0140-6736(23)00874-7.Peer-Reviewed Original ResearchConceptsLower-risk myelodysplastic syndromesRed blood cell transfusion independenceEpoetin alfa groupErythropoiesis-stimulating agentsEpoetin alfaMyelodysplastic syndromeInterim analysisPrimary endpointAdverse eventsAlfa groupTransfusion independenceLower riskBody weightTreatment-emergent adverse eventsTreatment-related adverse eventsRed blood cell transfusionDurable clinical efficacyMean hemoglobin increaseMedian treatment exposureBlood cell transfusionCOVID-19 pneumoniaSubgroup of patientsWeeks of treatmentTreatment of anemiaAcute myeloid leukemia
2022
Long-term utilization and benefit of luspatercept in patients (pts) with lower-risk myelodysplastic syndromes (LR-MDS) from the MEDALIST trial.
Fenaux P, Santini V, Komrokji R, Zeidan A, Garcia-Manero G, Buckstein R, Miteva D, Keeperman K, Holot N, Zhang J, Hughes C, Rosettani B, Yucel A, Platzbecker U. Long-term utilization and benefit of luspatercept in patients (pts) with lower-risk myelodysplastic syndromes (LR-MDS) from the MEDALIST trial. Journal Of Clinical Oncology 2022, 40: 7056-7056. DOI: 10.1200/jco.2022.40.16_suppl.7056.Peer-Reviewed Original ResearchLower-risk myelodysplastic syndromesAcute myeloid leukemiaErythropoiesis-stimulating agentsMedian cumulative durationCumulative durationRBC-TIMedian durationPlacebo armAML progressionRegular red blood cell transfusionsRed blood cell transfusionRBC transfusion independenceBlood cell transfusionHigh-risk MDSKaplan-Meier analysisLong-term followRate of progressionLong-term clinical valueEligible ptsCell transfusionPrimary endpointDurable responsesTransfusion independenceAML diagnosisDose escalation
2020
Feasibility of Peri-Transfusion Quality of Life Assessment for Patients with Myelodysplastic Syndromes
Abel G, Klepin H, Magnavita E, Jaung T, Shallis R, Bahl N, Dellinger-Johnston R, Winer E, Zeidan A. Feasibility of Peri-Transfusion Quality of Life Assessment for Patients with Myelodysplastic Syndromes. Blood 2020, 136: 25-26. DOI: 10.1182/blood-2020-139919.Peer-Reviewed Original ResearchECOG performance statusQuality of lifePerformance statusRBC transfusionMyelodysplastic syndromeExact testRed blood cell transfusionPatients' QOLDana-Farber Cancer InstituteTwo-sided Fisher's exact testMore RBC transfusionsPre-transfusion HbSetting of anemiaBlood cell transfusionHalf of patientsPost-transfusion increaseFisher's exact testCell transfusionPatient characteristicsUnstable anginaMedian HbMean ageTransfusion decisionsHb thresholdQoL assessment
2019
Assessment of Longer-Term Efficacy and Safety in the Phase 3, Randomized, Double-Blind, Placebo-Controlled MEDALIST Trial of Luspatercept to Treat Anemia in Patients (Pts) with Revised International Prognostic Scoring System (IPSS-R) Very Low-, Low-, or Intermediate-Risk Myelodysplastic Syndromes (MDS) with Ring Sideroblasts (RS) Who Require Red Blood Cell (RBC) Transfusions
Fenaux P, Mufti G, Buckstein R, Santini V, Díez-Campelo M, Finelli C, Cazzola M, Ilhan O, Sekeres M, Komrokji R, List A, Zeidan A, Verma A, Laadem A, Ito R, Zhang J, Rampersad A, Sinsimer D, Linde P, Garcia-Manero G, Platzbecker U. Assessment of Longer-Term Efficacy and Safety in the Phase 3, Randomized, Double-Blind, Placebo-Controlled MEDALIST Trial of Luspatercept to Treat Anemia in Patients (Pts) with Revised International Prognostic Scoring System (IPSS-R) Very Low-, Low-, or Intermediate-Risk Myelodysplastic Syndromes (MDS) with Ring Sideroblasts (RS) Who Require Red Blood Cell (RBC) Transfusions. Blood 2019, 134: 841. DOI: 10.1182/blood-2019-123064.Peer-Reviewed Original ResearchErythropoiesis-stimulating agentsIntermediate-risk myelodysplastic syndromesRBC-TIClinical benefitMyelodysplastic syndromeData cutoffHighest dose levelTransfusion burdenCelgene CorporationRing sideroblastsSpeakers bureauMedian durationDose levelsInternational Working Group 2006 criteriaClass erythroid maturation agentGrade 1Red blood cell transfusionInternational Prognostic Scoring SystemLower-risk myelodysplastic syndromesAdvisory CommitteeLow-risk MDSRBC transfusion independenceRegular RBC transfusionsMedian treatment durationBlood cell transfusionA Phase I Study of CC-90002, a Monoclonal Antibody Targeting CD47, in Patients with Relapsed and/or Refractory (R/R) Acute Myeloid Leukemia (AML) and High-Risk Myelodysplastic Syndromes (MDS): Final Results
Zeidan A, DeAngelo D, Palmer J, Seet C, Tallman M, Wei X, Li Y, Hock N, Burgess M, Hege K, Stock W. A Phase I Study of CC-90002, a Monoclonal Antibody Targeting CD47, in Patients with Relapsed and/or Refractory (R/R) Acute Myeloid Leukemia (AML) and High-Risk Myelodysplastic Syndromes (MDS): Final Results. Blood 2019, 134: 1320. DOI: 10.1182/blood-2019-125363.Peer-Reviewed Original ResearchTreatment-emergent adverse eventsR AMLHigh-risk myelodysplastic syndromeAnti-drug antibodiesAcute myeloid leukemiaMyelodysplastic syndromeADC therapeuticsJazz PharmaceuticalsDaiichi SankyoCelgene CorporationFebrile neutropeniaDose levelsDevelopment of ADAGrade treatment-emergent adverse eventsSerious treatment-emergent adverse eventsGeneral physical health deteriorationPhase I multicenter studyPrior stem cell transplantRefractory acute myeloid leukemiaRed blood cell transfusionBCR-ABL kinase domainAdvisory CommitteeAnti-CD47 monoclonal antibodyExcess blasts-2Grade 4 sepsisRBC transfusion independence among lower risk MDS patients receiving hypomethylating agents: a population-level analysis
Zeidan AM, Zhu W, Stahl M, Wang R, Huntington SF, Giri S, Podoltsev NA, Gore SD, Ma X, Davidoff AJ. RBC transfusion independence among lower risk MDS patients receiving hypomethylating agents: a population-level analysis. Leukemia & Lymphoma 2019, 60: 3181-3187. PMID: 31170846, DOI: 10.1080/10428194.2019.1622700.Peer-Reviewed Original ResearchConceptsRBC transfusion independenceLR-MDS patientsTransfusion independenceHMA initiationRBC transfusionClinical effectivenessReal-life clinical effectivenessRed blood cell transfusionLower-risk myelodysplastic syndromesLow-risk MDS patientsRisk MDS patientsBlood cell transfusionRisk myelodysplastic syndromesHMA therapyLR-MDSCell transfusionMost patientsDisease courseMDS patientsMedicare databaseMyelodysplastic syndromePopulation-level estimatesLower oddsTransfusionPatients
2018
Transfusion Independence in Lower-Risk, Non-del5(q) Myelodysplastic Syndromes (LR-MDS) Among Patients (pts) Initiating Hypomethylating Agents (HMAs) While Receiving Red Blood Cell (RBC) Transfusions
Zeidan A, Zhu W, Wang R, Stahl M, Huntington S, Giri S, Podoltsev N, Gore S, Ma X, Davidoff A. Transfusion Independence in Lower-Risk, Non-del5(q) Myelodysplastic Syndromes (LR-MDS) Among Patients (pts) Initiating Hypomethylating Agents (HMAs) While Receiving Red Blood Cell (RBC) Transfusions. Blood 2018, 132: 838. DOI: 10.1182/blood-2018-99-116497.Peer-Reviewed Original ResearchRBC transfusion independenceHMA initiationTransfusion independenceTransfusion dependenceLR-MDSClinical trial dataHypomethylating agentTransfusion statusMedian timeMedian TI durationCox modelContinuous Medicare Parts ATrial dataRed blood cell transfusionDiagnosis of MDSRBC transfusion dependenceSubset of ptsBlood cell transfusionEnd Results-MedicareErythropoiesis-stimulating agentsHigh-risk diseaseMultivariate Cox modelTreatment of MDSEnd of studyTI durationThe Medalist Trial: Results of a Phase 3, Randomized, Double-Blind, Placebo-Controlled Study of Luspatercept to Treat Anemia in Patients with Very Low-, Low-, or Intermediate-Risk Myelodysplastic Syndromes (MDS) with Ring Sideroblasts (RS) Who Require Red Blood Cell (RBC) Transfusions
Fenaux P, Platzbecker U, Mufti G, Garcia-Manero G, Buckstein R, Santini V, Díez-Campelo M, Finelli C, Cazzola M, Ilhan O, Sekeres M, Falantes J, Arrizabalaga B, Salvi F, Giai V, Vyas P, Bowen D, Selleslag D, DeZern A, Jurcic J, Germing U, Götze K, Quesnel B, Beyne-Rauzy O, Cluzeau T, Voso M, Mazure D, Vellenga E, Greenberg P, Hellström-Lindberg E, Zeidan A, Laadem A, Benzohra A, Zhang J, Rampersad A, Linde P, Sherman M, Komrokji R, List A. The Medalist Trial: Results of a Phase 3, Randomized, Double-Blind, Placebo-Controlled Study of Luspatercept to Treat Anemia in Patients with Very Low-, Low-, or Intermediate-Risk Myelodysplastic Syndromes (MDS) with Ring Sideroblasts (RS) Who Require Red Blood Cell (RBC) Transfusions. Blood 2018, 132: 1. DOI: 10.1182/blood-2018-99-110805.Peer-Reviewed Original ResearchIntermediate-risk myelodysplastic syndromesErythropoiesis-stimulating agentsIU/LKey secondary endpointMyelodysplastic syndromeRBC-TIRBC transfusionRing sideroblastsSpeakers bureauSecondary endpointsPrimary endpointWeek 1Class erythroid maturation agentRed blood cell transfusionInternational Prognostic Scoring SystemLower-risk myelodysplastic syndromesAdvisory CommitteeAbsence of transfusionIWG 2006 criteriaMean hemoglobin increaseRBC transfusion dependenceRBC transfusion independencePatient baseline characteristicsPlacebo-controlled studyBlood cell transfusionThe effect of iron chelation therapy on overall survival in sickle cell disease and β‐thalassemia: A systematic review
Ballas SK, Zeidan AM, Duong VH, DeVeaux M, Heeney MM. The effect of iron chelation therapy on overall survival in sickle cell disease and β‐thalassemia: A systematic review. American Journal Of Hematology 2018, 93: 943-952. PMID: 29635754, DOI: 10.1002/ajh.25103.Peer-Reviewed Original ResearchConceptsIron chelation therapySickle cell diseaseEvent-free survivalChelation therapyOverall survivalCell diseaseΒ-thalassemiaSystematic reviewRed blood cell transfusionBlood cell transfusionBetter overall survivalSerum ferritin levelsLife-threatening anemiaTransfusion-dependent patientsStandard of careIron chelation agentsLiver iron contentNew oral drugsCell transfusionFrequent transfusionsOral agentsDiabetes mellitusHeart failureLiver cirrhosisFerritin levels
2017
Overcoming barriers to treating iron overload in patients with lower-risk myelodysplastic syndrome
Zeidan AM, Pullarkat VA, Komrokji RS. Overcoming barriers to treating iron overload in patients with lower-risk myelodysplastic syndrome. Critical Reviews In Oncology/Hematology 2017, 117: 57-66. PMID: 28807236, DOI: 10.1016/j.critrevonc.2017.07.002.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsIron chelation therapyIron overloadMyelodysplastic syndromeFrequent red blood cell transfusionsLower-risk myelodysplastic syndromesRed blood cell transfusionLow-risk MDS patientsHeterogeneous hematopoietic neoplasmsRandomized trial evidenceBlood cell transfusionAcute myeloid leukemiaTissue iron depositionCell transfusionSupportive careMDS patientsTrial evidenceMyeloid leukemiaChelation therapyThalassemia patientsIneffective erythropoiesisBetter survivalPatientsEndocrine toxicityIron depositionHematopoietic neoplasms
2015
North American Cooperative Group Members' Patterns of Blood Products Transfusion for Patients with Acute Leukemia
Pine A, Lee E, Sekeres M, Steensma D, Prebet T, DeZern A, Komrokji R, Litzow M, Luger S, Stone R, Erba H, Garcia-Manero G, Lee A, Podoltsev N, Barbarotta L, Hendrickson J, Gore S, Zeidan A. North American Cooperative Group Members' Patterns of Blood Products Transfusion for Patients with Acute Leukemia. Blood 2015, 126: 1138. DOI: 10.1182/blood.v126.23.1138.1138.Peer-Reviewed Original ResearchRed blood cell transfusionNon-bleeding patientsBlood cell transfusionBone marrow biopsyBlood product transfusionSouthwest Oncology GroupPlatelet transfusionsOutpatient settingAcute leukemiaPlatelet levelsCell transfusionHemoglobin levelsTransfusion practiceLumbar punctureFibrinogen levelsProduct transfusionHospitalized patientsOncology GroupClinical trialsPlatelet thresholdMost respondersConsensus evidence-based guidelinesMost providersEastern Cooperative Oncology GroupStable hospitalized patientsVariations in erythropoiesis-stimulating agent administration in transfusion-dependent myelodysplastic syndromes impact response
Duong VH, Baer MR, Hendrick F, Weiss SR, Sato M, Zeidan AM, Gore SD, Davidoff AJ. Variations in erythropoiesis-stimulating agent administration in transfusion-dependent myelodysplastic syndromes impact response. Leukemia Research 2015, 39: 586-591. PMID: 25869077, PMCID: PMC4441842, DOI: 10.1016/j.leukres.2015.03.013.Peer-Reviewed Original ResearchConceptsErythropoiesis-stimulating agentsUse of darbepoetinTransfusion independenceESA initiationTransfusion dependenceMyelodysplastic syndromeESA useTransfusion-dependent MDS patientsRed blood cell transfusionNumber of weeksCox proportional hazards modelErythropoiesis-stimulating agent administrationEnd Results-MedicareWeeks of therapyBlood cell transfusionWeeks of treatmentPopulation-based studyKaplan-Meier statisticsProportional hazards modelAssociation of timingHigh response rateCell transfusionEarly administrationSurveillance EpidemiologyESA administration