2024
Targeted therapies for myelodysplastic syndromes/neoplasms (MDS): current landscape and future directions
Bidikian A, Bewersdorf J, Shallis R, Getz T, Stempel J, Kewan T, Stahl M, Zeidan A. Targeted therapies for myelodysplastic syndromes/neoplasms (MDS): current landscape and future directions. Expert Review Of Anticancer Therapy 2024, 24: 1131-1146. PMID: 39367718, DOI: 10.1080/14737140.2024.2414071.Peer-Reviewed Original ResearchErythropoiesis-stimulating agentsTargeted therapyLR-MDSHR-MDSHypoxia-inducible factorAllogeneic hematopoietic stem cell transplantationLandscape of targeted therapiesHematopoietic stem cell transplantationHeterogeneous group of hematologic malignanciesGroup of hematologic malignanciesMolecular prognostic toolsDuration of responseStem cell transplantationTrial designClinical trial designHypomethylating agentsCell transplantationHematologic malignanciesImprove patient outcomesRNA splicing machineryImmune evasionPrognostic toolTGF-betaTherapyEffective treatmentMDS-156 Efficacy of Imetelstat on Red Blood Cell (RBC)-Transfusion Independence (TI) in the Absence of Platelet Transfusions or Myeloid Growth Factors (MGF) in IMerge
Zeidan A, Santini V, Platzbecker U, Sekeres M, Savona M, Fenaux P, Madanat Y, Raza A, Xia Q, Sun L, Riggs J, Shah S, Navada S, Berry T, Komrokji R. MDS-156 Efficacy of Imetelstat on Red Blood Cell (RBC)-Transfusion Independence (TI) in the Absence of Platelet Transfusions or Myeloid Growth Factors (MGF) in IMerge. Clinical Lymphoma Myeloma & Leukemia 2024, 24: s386. DOI: 10.1016/s2152-2650(24)01344-2.Peer-Reviewed Original ResearchLower-risk myelodysplastic syndromesMyeloid growth factorsErythropoiesis-stimulating agentsRBC-TIPlatelet transfusionsTransfusion-dependentHb levelsLong-term respondersPercentage of patientsHb riseRBC-TDPlacebo patientsNon-del(5qMyelodysplastic syndromePlacebo groupPrimary endpointSecondary endpointsInvestigator's discretionClinical benefitPlaceboAnalysis cutoffImetelstatDisease progressionTransfusionSupportive careMDS-157 Overall Survival (OS), Clinical Benefit, and Durable Red Blood Cell (RBC) Transfusion Independence (TI) With Imetelstat in the IMerge Phase 3 Trial of RBC-Transfusion Dependent (TD) Lower-Risk Myelodysplastic Syndromes (LR-MDS)
Santini V, Komrokji R, Sekeres M, Savona M, Fenaux P, Madanat Y, Oliva E, Buckstein R, Annaášová A, Germing U, Mittelman M, Thepot S, Riggs J, Dougherty S, Berry T, Navada S, Xia Q, Sun L, Zeidan A, Platzbecker U. MDS-157 Overall Survival (OS), Clinical Benefit, and Durable Red Blood Cell (RBC) Transfusion Independence (TI) With Imetelstat in the IMerge Phase 3 Trial of RBC-Transfusion Dependent (TD) Lower-Risk Myelodysplastic Syndromes (LR-MDS). Clinical Lymphoma Myeloma & Leukemia 2024, 24: s386-s387. DOI: 10.1016/s2152-2650(24)01345-4.Peer-Reviewed Original ResearchLower-risk myelodysplastic syndromesNon-del(5q) lower-risk myelodysplastic syndromesErythropoiesis-stimulating agentsRBC-TIOverall survivalRBC-TDNon-del(5qClinical benefitRed blood cellsHemoglobin increaseRBC transfusion dependenceStratified log-rank testMedian follow-upKaplan-Meier methodLog-rank testWithdrawal of consentMedian OSOS ratesHemoglobin riseMyelodysplastic syndromeOS analysisHemoglobin levelsAssess OSPlaceboImetelstatTreatment of Myelodysplastic Syndromes for Older Patients: Current State of Science, Challenges, and Opportunities
Kewan T, Stahl M, Bewersdorf J, Zeidan A. Treatment of Myelodysplastic Syndromes for Older Patients: Current State of Science, Challenges, and Opportunities. Current Hematologic Malignancy Reports 2024, 19: 138-150. PMID: 38632155, DOI: 10.1007/s11899-024-00733-y.Peer-Reviewed Original ResearchHematopoietic stem cell transplantationAllogeneic hematopoietic stem cell transplantationLower-risk MDSErythropoiesis-stimulating agentsHypomethylating agentsIPSS-MHR-MDSRisk stratificationMolecular International Prognostic Scoring SystemRisk of leukemia progressionTreated with hypomethylating agentsInternational Prognostic Scoring SystemTreatment of myelodysplastic syndromesOral hypomethylating agentsHigh-risk MDSPrognostic Scoring SystemStem cell transplantationEnhanced risk stratificationRecent FindingsRecent advancesRefine treatment strategiesQuality-of-life improvementAssociated with treatmentTreatment decision-makingIntensive chemotherapyMDS patients
2023
Imetelstat in patients with lower-risk myelodysplastic syndromes who have relapsed or are refractory to erythropoiesis-stimulating agents (IMerge): a multinational, randomised, double-blind, placebo-controlled, phase 3 trial
Platzbecker U, Santini V, Fenaux P, Sekeres M, Savona M, Madanat Y, Díez-Campelo M, Valcárcel D, Illmer T, Jonášová A, Bělohlávková P, Sherman L, Berry T, Dougherty S, Shah S, Xia Q, Sun L, Wan Y, Huang F, Ikin A, Navada S, Feller F, Komrokji R, Zeidan A. Imetelstat in patients with lower-risk myelodysplastic syndromes who have relapsed or are refractory to erythropoiesis-stimulating agents (IMerge): a multinational, randomised, double-blind, placebo-controlled, phase 3 trial. The Lancet 2023, 403: 249-260. PMID: 38048786, DOI: 10.1016/s0140-6736(23)01724-5.Peer-Reviewed Original ResearchLower-risk myelodysplastic syndromesErythropoiesis-stimulating agentsPlacebo groupAdverse eventsMyelodysplastic syndromeGrade 3Subsequent anti-cancer therapyTreatment-emergent adverse eventsTreatment-emergent grade 3Days of randomisationIPSS risk groupRBC transfusion burdenTransfusion independence rateTreatment-related deathsUnacceptable toxic effectsPlacebo-controlled trialDisease-modifying activityPhase 2 trialPhase 3 trialPrimary efficacy analysisProportion of patientsWithdrawal of consentUnmet medical needComputer-generated scheduleAnti-cancer therapyThe 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 studyCharacterization and Management of Cytopenias after Imetelstat Treatment in the IMerge Phase 3 Trial of Patients with Lower-Risk Myelodysplastic Syndromes (LR-MDS)
Zeidan A, Savona M, Madanat Y, Fenaux P, Komrokji R, Jonášová A, Illmer T, Sun L, Berry T, Feller F, Navada S, Santini V, Platzbecker U. Characterization and Management of Cytopenias after Imetelstat Treatment in the IMerge Phase 3 Trial of Patients with Lower-Risk Myelodysplastic Syndromes (LR-MDS). Blood 2023, 142: 6478. DOI: 10.1182/blood-2023-180962.Peer-Reviewed Original ResearchTreatment-emergent adverse eventsLower-risk myelodysplastic syndromesPhase 3 trialManagement of cytopeniasGrade 3Placebo groupDose adjustmentMedian timeTreatment delayDose reductionInternational Prognostic Scoring System risk groupsHematologic treatment-emergent adverse eventsRed blood cell transfusion dependencyImetelstat treatmentExperienced grade 3RBC transfusion burdenRBC transfusion independenceTreatment cycles 1Grade 4 neutropeniaGrade 4 thrombocytopeniaPrimary end pointGrowth factor supportErythropoiesis-stimulating agentsCycle 1High telomerase activityImpact of Mutational Status on Clinical Response to Imetelstat in Patients with Lower-Risk Myelodysplastic Syndromes in the IMerge Phase 3 Study
Santini V, Zeidan A, Fenaux P, Madanat Y, Berry T, Feller F, Sun L, Xia Q, Wan Y, Huang F, Savona M, Platzbecker U. Impact of Mutational Status on Clinical Response to Imetelstat in Patients with Lower-Risk Myelodysplastic Syndromes in the IMerge Phase 3 Study. Blood 2023, 142: 4603. DOI: 10.1182/blood-2023-179378.Peer-Reviewed Original ResearchLower-risk myelodysplastic syndromesPlacebo groupTransfusion independenceTI ratesHot spot mutationsPoor prognosisMyelodysplastic syndromeRed blood cell transfusion independenceASXL1 mutationsErythropoiesis-stimulating agentsPhase 3 studyStudy of patientsTI responsesPresence of mutationsSpecific mutationsClinical responseStudy entryClinical efficacyClinical benefitPeripheral bloodMutation subgroupsDNMT3A mutationsEpigenetic modifiersPatientsRUNX1 mutationsImpact 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 mutationsUpdates 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 needsEfficacy 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 leukemiaNovel 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 testingWhy 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 mutationsApprovalInflammation
2022
Longer-term benefit of luspatercept in transfusion-dependent lower-risk myelodysplastic syndromes with ring sideroblasts
Zeidan AM, Platzbecker U, Garcia-Manero G, Sekeres MA, Fenaux P, DeZern AE, Greenberg PL, Savona MR, Jurcic JG, Verma A, Mufti G, Buckstein R, Santini V, Shetty JK, Ito R, Zhang J, Zhang G, Ha X, Backstrom JT, Komrokji RS. Longer-term benefit of luspatercept in transfusion-dependent lower-risk myelodysplastic syndromes with ring sideroblasts. Blood 2022, 140: 2170-2174. PMID: 35797468, PMCID: PMC10653038, DOI: 10.1182/blood.2022016171.Peer-Reviewed Original ResearchConceptsLower-risk myelodysplastic syndromesLow-risk myelodysplasiaErythropoiesis-stimulating agentsEligible patientsTransfusion independenceMyelodysplastic syndromeLong-term benefitsLuspaterceptMedian durabilityRing sideroblastsPatientsIncremental benefitPlaceboSignificant minorityTherapyTransfusionMyelodysplasiaSideroblastsSyndromeTrialsWeeksMonthsLong-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
2021
Analysis of Duration of Response, Exposure-Adjusted Safety and Progression to Acute Myeloid Leukemia (AML) for Patients with Lower-Risk Myelodysplastic Syndromes (LR-MDS) Receiving Luspatercept in the MEDALIST Study
Platzbecker U, Santini V, Komrokji R, Zeidan A, Garcia-Manero G, Buckstein R, Rose S, Fabre S, Miteva D, Zhang J, Yucel A, Hughes C, Fenaux P. Analysis of Duration of Response, Exposure-Adjusted Safety and Progression to Acute Myeloid Leukemia (AML) for Patients with Lower-Risk Myelodysplastic Syndromes (LR-MDS) Receiving Luspatercept in the MEDALIST Study. Blood 2021, 138: 1524. DOI: 10.1182/blood-2021-145723.Peer-Reviewed Original ResearchLower-risk myelodysplastic syndromesTreatment-emergent adverse eventsClinical Trials CommitteeAcute myeloid leukemiaErythropoiesis-stimulating agentsExposure-adjusted incidence ratesRBC-TITrials CommitteeEntire treatment periodDuration of treatmentRing sideroblastsAML progressionCurrent equity holderMedian durationTreatment optionsIncidence rateTreatment periodWk 1Only treatment-emergent adverse eventClass erythroid maturation agentMDS/myeloproliferative neoplasmAdvisory CommitteeRegular RBC transfusionsTolerable safety profileSpeakers bureauIMerge: A phase 3 study to evaluate imetelstat in transfusion-dependent subjects with IPSS low or intermediate-1 risk myelodysplastic syndromes that are relapsed/refractory to erythropoiesis-stimulating agent treatment.
Platzbecker U, Komrokji R, Fenaux P, Zeidan A, Sekeres M, Savona M, Madanat Y, Sherman L, Dougherty S, Sun L, Huang F, Wan Y, Rizo A, Berry T, Feller F, Santini V. IMerge: A phase 3 study to evaluate imetelstat in transfusion-dependent subjects with IPSS low or intermediate-1 risk myelodysplastic syndromes that are relapsed/refractory to erythropoiesis-stimulating agent treatment. Journal Of Clinical Oncology 2021, 39: tps7056-tps7056. DOI: 10.1200/jco.2021.39.15_suppl.tps7056.Peer-Reviewed Original ResearchInternational Prognostic Scoring SystemErythropoiesis-stimulating agentsPhase 3 partRisk myelodysplastic syndromesMyelodysplastic syndromeRBC-TIRed blood cell (RBC) transfusion-dependent patientsErythropoiesis-stimulating agent treatmentLower-risk myelodysplastic syndromesPhase 2 partProgression of MDSRBC transfusion independenceTransfusion dependent subjectsPlacebo-controlled trialPhase 2/3 studyPhase 3 studyPrognostic scoring systemCurrent treatment optionsTransfusion-dependent patientsQuality of lifeMedian TI durationRate of CRVariant allele frequencyMechanism of actionAdult pts
2020
MDS-179: Clinical Benefit of Luspatercept in Patients with Lower-Risk Myelodysplastic Syndromes (LR-MDS) and High Transfusion Burden (HTB) in the Phase 3 MEDALIST Study
Zeidan A, Garcia-Manero G, DeZern A, Fenaux P, Greenberg P, Savona M, Jurcic J, Verma A, Mufti G, Buckstein R, Santini V, Laadem A, Zhang J, Rampersad A, Sinsimer D, Louis C, Linde P, Platzbecker U, Sekeres M. MDS-179: Clinical Benefit of Luspatercept in Patients with Lower-Risk Myelodysplastic Syndromes (LR-MDS) and High Transfusion Burden (HTB) in the Phase 3 MEDALIST Study. Clinical Lymphoma Myeloma & Leukemia 2020, 20: s318-s319. DOI: 10.1016/s2152-2650(20)30973-3.Peer-Reviewed Original ResearchLower-risk myelodysplastic syndromesTreatment-emergent adverse eventsHigh transfusion burdenRBC transfusion independenceRing sideroblastsTransfusion burdenTransfusion eventsClinical benefitWeek 1Serious treatment-emergent adverse eventsSignificant clinical unmet needPlacebo-treated patientsRBC transfusion burdenRegular RBC transfusionsClinical unmet needErythropoiesis-stimulating agentsOverall study populationEligible patientsPlacebo patientsAdverse eventsMedian durationPlacebo armRBC transfusionMedian timeTreatment armsClinical benefit of luspatercept in patients (pts) with lower-risk MDS (LR-MDS) and high transfusion burden in the phase III MEDALIST study.
Zeidan A, Garcia-Manero G, Dezern A, Fenaux P, Greenberg P, Savona M, Jurcic J, Verma A, Mufti G, Buckstein R, Santini V, Laadem A, Zhang J, Rampersad A, Sinsimer D, Louis C, Linde P, List A, Sekeres M. Clinical benefit of luspatercept in patients (pts) with lower-risk MDS (LR-MDS) and high transfusion burden in the phase III MEDALIST study. Journal Of Clinical Oncology 2020, 38: 7554-7554. DOI: 10.1200/jco.2020.38.15_suppl.7554.Peer-Reviewed Original ResearchTreatment-emergent adverse eventsLow-risk MDSRBC transfusion burdenTransfusion burdenRing sideroblastsRBC-TITransfusion eventsClinical benefitWeek 1Significant clinical unmet needPT populationHigh transfusion burdenRBC transfusion independenceRegular RBC transfusionsAcceptable safety profilePhase 3 studyClinical unmet needErythropoiesis-stimulating agentsSerious AEsMedian durationAdverse eventsMedian timeRBC transfusionSafety profileTreatment optionsLuspatercept in Patients with Lower-Risk Myelodysplastic Syndromes
Fenaux P, Platzbecker U, Mufti GJ, Garcia-Manero G, Buckstein R, Santini V, Díez-Campelo M, Finelli C, Cazzola M, Ilhan O, Sekeres MA, Falantes JF, Arrizabalaga B, Salvi F, Giai V, Vyas P, Bowen D, Selleslag D, DeZern AE, Jurcic JG, Germing U, Götze KS, Quesnel B, Beyne-Rauzy O, Cluzeau T, Voso MT, Mazure D, Vellenga E, Greenberg PL, Hellström-Lindberg E, Zeidan AM, Adès L, Verma A, Savona MR, Laadem A, Benzohra A, Zhang J, Rampersad A, Dunshee DR, Linde PG, Sherman ML, Komrokji RS, List AF. Luspatercept in Patients with Lower-Risk Myelodysplastic Syndromes. New England Journal Of Medicine 2020, 382: 140-151. PMID: 31914241, DOI: 10.1056/nejmoa1908892.Peer-Reviewed Original ResearchConceptsLower-risk myelodysplastic syndromesRed cell transfusionKey secondary end pointRegular red cell transfusionsSecondary end pointsMyelodysplastic syndromeTransfusion independenceAdverse eventsWeek 1Placebo groupEnd pointRing sideroblastsErythropoiesis-stimulating agent therapyIntermediate-risk myelodysplastic syndromesPrimary end pointPhase 2 studyPhase 3 trialErythropoiesis-stimulating agentsSeverity of anemiaGrowth factor βBaseline characteristicsAgent therapyLuspaterceptPatientsSyndrome