2024
Efficacy of imetelstat on red blood cell (RBC)-transfusion independence (TI) in the absence of platelet transfusions or myeloid growth factors 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. Efficacy of imetelstat on red blood cell (RBC)-transfusion independence (TI) in the absence of platelet transfusions or myeloid growth factors in IMerge. Journal Of Clinical Oncology 2024, 42: 6566-6566. DOI: 10.1200/jco.2024.42.16_suppl.6566.Peer-Reviewed Original ResearchLower-risk myelodysplastic syndromesRBC-TIMyeloid growth factorsPlatelet transfusionsTransfusion-dependentHb levelsGrowth factorGrowth factor supportLong-term respondersGrowth factor useErythropoiesis stimulating agentsHb riseSevere neutropeniaMyelodysplastic syndromePlacebo groupPrimary endpointSecondary endpointsFactor supportInvestigator's discretionClinical benefitAdverse eventsPlaceboAnalysis cutoffImetelstatDisease progressionClinical 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 medianLuspaterceptEFFICACY AND SAFETY OF LUSPATERCEPT VERSUS EPOETIN ALFA IN ERYTHROPOIESIS-STIMULATING AGENT (ESA)-NAIVE PATIENTS WITH TRANSFUSION-DEPENDENT LOWER-RISK MYELODYSPLASTIC SYNDROMES (LR-MDS): FULL ANALYSIS OF THE COMMANDS TRIAL
Garcia-Manero G, Platzbecker U, Santini V, Zeidan A, Fenaux P, 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, Prebet T, Degulys A, Paolini S, Cluzeau T, Della Porta M. EFFICACY AND SAFETY OF LUSPATERCEPT VERSUS EPOETIN ALFA IN ERYTHROPOIESIS-STIMULATING AGENT (ESA)-NAIVE PATIENTS WITH TRANSFUSION-DEPENDENT LOWER-RISK MYELODYSPLASTIC SYNDROMES (LR-MDS): FULL ANALYSIS OF THE COMMANDS TRIAL. Leukemia Research Reports 2024, 21: 100447. DOI: 10.1016/j.lrr.2024.100447.Peer-Reviewed Original ResearchLower-risk myelodysplastic syndromesTreatment-emergent adverse eventsEA-treated patientsRBC-TIPrimary endpointHI-ERed blood cell transfusion independenceHematological improvement-erythroidTransfusion independenceErythroid responseMyelodysplastic syndromeSecondary endpointsAdverse eventsFull analysisLuspaterceptAssessed efficacySafety resultsEpoetin alfaTreatment durationPatientsEndpointEfficacyDurationPost-treatmentAML
2023
Efficacy of Imetelstat in Achieving Red Blood Cell Transfusion Independence (RBC-TI) across Different Risk Subgroups in Patients with Lower-Risk Myelodysplastic Syndromes (LR-MDS) Relapsed/Refractory (R/R) to Erythropoiesis-Stimulating Agents (ESAs) in IMerge Phase 3 Study
Komrokji R, Santini V, Fenaux P, Savona M, Madanat Y, Berry T, Sherman L, Navada S, Feller F, Sun L, Xia Q, Wan Y, Huang F, Zeidan A, Platzbecker U. Efficacy of Imetelstat in Achieving Red Blood Cell Transfusion Independence (RBC-TI) across Different Risk Subgroups in Patients with Lower-Risk Myelodysplastic Syndromes (LR-MDS) Relapsed/Refractory (R/R) to Erythropoiesis-Stimulating Agents (ESAs) in IMerge Phase 3 Study. Blood 2023, 142: 194. DOI: 10.1182/blood-2023-181237.Peer-Reviewed Original ResearchInternational Prognostic Scoring SystemLower-risk myelodysplastic syndromesDifferent risk subgroupsErythropoiesis stimulating agentsLow-risk subgroupsRisk groupsRisk subgroupsResponse rateTI ratesRBC-TIClinical efficacyRisk categoriesHigh riskLower riskRed blood cell transfusion independenceIPSS risk groupPhase 3 portionIntermediate-risk groupCytogenetic risk groupHigh-risk patientsPhase 3 studyPrognostic scoring systemIntermediate-risk subgroupsHigh-risk subgroupsHigh-risk groupLong-Term Evaluation of Luspatercept in Erythropoiesis-Stimulating Agent (ESA)-Intolerant/Refractory Patients (pts) with Lower-Risk Myelodysplastic Syndromes (LR-MDS) in the Phase 3 MEDALIST Study
Santini V, Komrokji R, Garcia-Manero G, Buckstein R, Oliva E, Keeperman K, Rose S, Giuseppi A, Vilmont V, Lai Y, Miteva D, Aggarwal B, Platzbecker U, Fenaux P, Zeidan A. Long-Term Evaluation of Luspatercept in Erythropoiesis-Stimulating Agent (ESA)-Intolerant/Refractory Patients (pts) with Lower-Risk Myelodysplastic Syndromes (LR-MDS) in the Phase 3 MEDALIST Study. Blood 2023, 142: 915. DOI: 10.1182/blood-2023-178546.Peer-Reviewed Original ResearchLower-risk myelodysplastic syndromesTreatment-emergent adverse eventsLong-term efficacyEntire treatment periodExposure-adjusted incidence ratesMedian cumulative durationRBC-TITreatment periodCumulative durationData cutoffTreatment-related treatment-emergent adverse eventsCommon treatment-emergent adverse eventsRed blood cell transfusion independencePrevious short-term reportsLong-term safety profileAcute myeloid leukemia progressionRegular RBC transfusionsPermanent treatment discontinuationKaplan-Meier analysisErythropoiesis stimulating agentsShort-term reportsMyeloid leukemia progressionEligible ptsHR-MDSRefractory patientsImproved benefit of continuing luspatercept therapy: sub-analysis of patients with lower-risk MDS in the MEDALIST study
Germing U, Fenaux P, Platzbecker U, Buckstein R, Santini V, Díez-Campelo M, Yucel A, Tang D, Fabre S, Zhang G, Zoffoli R, Ha X, Miteva D, Hughes C, Komrokji R, Zeidan A, Garcia-Manero G. Improved benefit of continuing luspatercept therapy: sub-analysis of patients with lower-risk MDS in the MEDALIST study. Annals Of Hematology 2023, 102: 311-321. PMID: 36635381, PMCID: PMC9889415, DOI: 10.1007/s00277-022-05071-8.Peer-Reviewed Original ResearchConceptsRBC transfusion burdenTransfusion burdenWeek 25Transfusion unitsRBC-TIInitial nonrespondersHemoglobin levelsErythroid responseClinical benefitRed blood cell transfusion independenceLower-risk myelodysplastic syndromesPlacebo-treated patientsSerum ferritin levelsAdditional clinical benefitWeeks of treatmentLower-risk MDSTransfusion independenceFerritin levelsSerum ferritinMyelodysplastic syndromeRing sideroblastsPatientsClinical practiceLuspaterceptMaximum dose
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
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
Efficacy and Safety of Luspatercept Treatment in Patients with Myelodysplastic Syndrome/Myeloproliferative Neoplasm with Ring Sideroblasts and Thrombocytosis (MDS/MPN-RS-T): A Retrospective Analysis from the Medalist Study
Komrokji R, Platzbecker U, Fenaux P, Garcia-Manero G, Mufti G, Santini V, Diez-Campelo M, Finelli C, Jurcic J, Greenberg P, Sekeres M, Zeidan A, DeZern A, Savona M, Shetty J, Ito R, Zhang G, Ha X, Sinsimer D, Backstrom J, Verma A. Efficacy and Safety of Luspatercept Treatment in Patients with Myelodysplastic Syndrome/Myeloproliferative Neoplasm with Ring Sideroblasts and Thrombocytosis (MDS/MPN-RS-T): A Retrospective Analysis from the Medalist Study. Blood 2020, 136: 13-15. DOI: 10.1182/blood-2020-137232.Peer-Reviewed Original ResearchMDS/MPN-RSCurrent equity holderMedian leukocyte countMedian platelet countPlacebo armRing sideroblastsSpeakers bureauRBC-TIPrimary endpointClinical benefitPlatelet countTreatment optionsLeukocyte countRetrospective analysisMyelodysplastic syndrome/myeloproliferative neoplasmClass erythroid maturation agentMean serum ferritin levelWk 1Boehringer IngelheimAdvisory CommitteeDaiichi SankyoClinical benefit responseMean Hb increaseRBC transfusion independenceRegular RBC transfusionsMDS-175: Assessment of Dose-Dependent Response to Luspatercept in Patients with Lower-Risk Myelodysplastic Syndromes (LR-MDS) with Ring Sideroblasts (RS) in the Phase 3 MEDALIST Trial
Platzbecker U, Fenaux P, Mufti G, Garcia-Manero G, Komrokji R, Buckstein R, Diez-Campelo M, Finelli C, Sekeres M, Selleslag D, DeZern A, Quesnel B, Beyne-Rauzy O, Voso M, Greenberg P, Zeidan A, Adès L, Verma A, Savona M, Laadem A, Ito R, Zhang J, Rampersad A, Morison J, Louis C, Linde P, Santini V. MDS-175: Assessment of Dose-Dependent Response to Luspatercept in Patients with Lower-Risk Myelodysplastic Syndromes (LR-MDS) with Ring Sideroblasts (RS) in the Phase 3 MEDALIST Trial. Clinical Lymphoma Myeloma & Leukemia 2020, 20: s318. DOI: 10.1016/s2152-2650(20)30972-1.Peer-Reviewed Original ResearchTreatment-emergent adverse eventsLower-risk myelodysplastic syndromesRBC-TIRing sideroblastsDose levelsDose reductions/delaysMaximum doseLR-MDS patientsRBC transfusion independenceMajority of patientsMaintenance of responseSame dose levelFirst responseDose delaysDose-dependent responseEligible patientsDose titrationNew onsetTransfusion burdenTransfusion independenceAdverse eventsDose escalationMedian timeMyelodysplastic syndromeHemoglobin increaseClinical 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 options
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 transfusion
2018
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
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 transfusion