2024
Sustained benefits of imetelstat on patient-reported fatigue in patients with lower-risk myelodysplastic syndromes ineligible for, or relapsed/refractory to, erythropoiesis-stimulating agents and high transfusion burden in the phase 3 IMerge study
Sekeres M, Santini V, Díez-Campelo M, Komrokji R, Fenaux P, Savona M, Madanat Y, Valcárcel-Ferreiras D, Oliva E, Regnault A, Creel K, Sengupta N, Dougherty S, Shah S, Sun L, Wan Y, Navada S, Zeidan A, Platzbecker U. Sustained benefits of imetelstat on patient-reported fatigue in patients with lower-risk myelodysplastic syndromes ineligible for, or relapsed/refractory to, erythropoiesis-stimulating agents and high transfusion burden in the phase 3 IMerge study. Leukemia & Lymphoma 2024, ahead-of-print: 1-6. PMID: 39535901, DOI: 10.1080/10428194.2024.2426057.Peer-Reviewed Original ResearchChanges in Red Blood Cell Transfusion Burden with Luspatercept Versus Epoetin Alfa in Patients with Lower-Risk Myelodysplastic Syndromes in the Phase 3, Open-Label, Randomized, Controlled COMMANDS Trial
Garcia-Manero G, Della Porta M, Santini V, Zeidan A, Komrokji R, Fenaux P, Valcárcel D, Shortt J, Glassberg M, Yucel A, Lai Y, Miteva D, Rose S, Hnoosh A, Platzbecker U. Changes in Red Blood Cell Transfusion Burden with Luspatercept Versus Epoetin Alfa in Patients with Lower-Risk Myelodysplastic Syndromes in the Phase 3, Open-Label, Randomized, Controlled COMMANDS Trial. Blood 2024, 144: 1832-1832. DOI: 10.1182/blood-2024-198304.Peer-Reviewed Original ResearchRegular red blood cell transfusionsLower-risk myelodysplastic syndromesErythropoiesis-stimulating agentsTreated with epoetin alfaEpoetin alfaRBC unitsLuspatercept treatmentTransfusion burdenMyelodysplastic syndromeOpen-labelFirst-in-class erythroid maturation agentRed blood cell transfusion burdenEfficacy of erythropoiesis-stimulating agentsRed blood cell transfusionErythroid maturation agentBlood cell transfusionBaseline Hb levelsArm of treatmentRBC-TICell transfusionMedian ageResponse durabilityChronic anemiaHb levelsLuspaterceptCorrelation of Patient-Reported Outcomes with Red Blood Cell Transfusion Reduction and Rise in Hemoglobin in Patients with Lower-Risk Myelodysplastic Syndromes in the IMerge Trial
Sekeres M, Santini V, Zeidan A, Platzbecker U, Komrokji R, Diez-Campelo M, Fenaux P, Savona M, Madanat Y, Valcarcel D, Regnault A, Creel K, Sengupta N, Dougherty S, Shah S, Sun L, Wan Y, Navada S, Oliva E. Correlation of Patient-Reported Outcomes with Red Blood Cell Transfusion Reduction and Rise in Hemoglobin in Patients with Lower-Risk Myelodysplastic Syndromes in the IMerge Trial. Blood 2024, 144: 3210. DOI: 10.1182/blood-2024-199636.Peer-Reviewed Original ResearchLower-risk myelodysplastic syndromesErythropoiesis-stimulating agentsPatient-reported outcomesFunctional Assessment of Cancer Therapy-AnemiaRed blood cellsAnemia symptomsQuality of lifeRBC-TDRBC-TITransfusion burdenPlacebo recipientsTransfusion independenceMyelodysplastic syndromeTransfusion reductionRed blood cell transfusion independenceFunctional Assessment of Chronic Illness Therapy (FACIT)-FatigueBaseline to cycleUnited States Food and Drug AdministrationStates Food and Drug AdministrationCorrelations of patient-reported outcomesFirst-in-classFunctional assessmentFood and Drug AdministrationMaintenance of quality of lifePost hoc analysisRenew Trial in Progress: A Phase 3, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Elritercept (KER-050) for the Treatment of Transfusion-Dependent Anemia in Adult Participants with Very Low-, Low-, or Intermediate-Risk Myelodysplastic Neoplasms (MDS)
Komrokji R, Diez-Campelo M, Chee L, Cluzeau T, DeZern A, Fenaux P, Garcia-Manero G, Giagounidis A, Platzbecker U, Della Porta M, Santini V, Sekeres M, Zeidan A, Buckstein R, Ross M, Jiang Y, Bobba S, Hankin M, Materna C, Graham C, Thamake S, Rovaldi C, Grayson D, Salstrom J. Renew Trial in Progress: A Phase 3, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Elritercept (KER-050) for the Treatment of Transfusion-Dependent Anemia in Adult Participants with Very Low-, Low-, or Intermediate-Risk Myelodysplastic Neoplasms (MDS). Blood 2024, 144: 3228.1-3228.1. DOI: 10.1182/blood-2024-200797.Peer-Reviewed Original ResearchDurability of responseMyelodysplastic neoplasmsFollow-up periodTransfusion burdenProportion of participantsAdverse eventsTransfusion independenceIneffective hematopoiesisDouble-blindPlacebo-controlled phase 3 studyAchievement of transfusion independenceMultiple stages of hematopoiesisSafety follow-up periodDouble-blind treatment periodLong-term follow-up periodSeverity of adverse eventsLong-term follow-upErythroid maturation agentLow transfusion burdenSustained hematologic improvementTreatment of transfusion-dependent anemiaPlacebo-controlled studyTransfusion-dependent anemiaPhase 3 studyProgression to AMLA Phase 2B, Open-Label Multicenter Study of Tebapivat (AG-946), a Potent Pyruvate Kinase Activator, in Patients with Anemia Due to Lower-Risk Myelodysplastic Syndromes
Zeidan A, Sekeres M, Al-Samkari H, Carraway H, DeZern A, Mittelman M, Little M, Beynon V, Dai X, Sommakia S, Despotovic J, Patel P, Dibacco M, Fattizzo B, Stein E, Sallman D, Kulasekararaj A, Platzbecker U, Fenaux P. A Phase 2B, Open-Label Multicenter Study of Tebapivat (AG-946), a Potent Pyruvate Kinase Activator, in Patients with Anemia Due to Lower-Risk Myelodysplastic Syndromes. Blood 2024, 144: 6708-6708. DOI: 10.1182/blood-2024-203073.Peer-Reviewed Original ResearchLower-risk MDSErythropoiesis-stimulating agentsLower-risk myelodysplastic syndromesRed blood cell unitsMyelodysplastic syndromeProportion of patientsDose levelsRed blood cellsIPSS-RTransfusion burdenOpen-labelFirst doseRevised International Prognostic Scoring SystemHistory of acute myeloid leukemiaMDS mouse modelsMedian duration of responsePhase 2bInternational Prognostic Scoring SystemOpen-label multicenter studyAssociated with increased morbidityBone marrow neoplasmsHigh transfusion burdenIPSS-R scoreLow transfusion burdenDose level 1MDS-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 medianLuspatercept
2023
Improvement of Patient-Reported Outcomes Among Heavily Pretreated Patients with Lower-Risk Myelodysplastic Syndromes and High Transfusion Burden Treated with Imetelstat on the IMerge Phase 3 Trial
Sekeres M, Diez-Campelo M, Zeidan A, Platzbecker U, Regnault A, Creel K, Sengupta N, Wan Y, Sun L, Xia Q, Berry T, Dougherty S, Shah S, Navada S, Santini V, Valcárcel D. Improvement of Patient-Reported Outcomes Among Heavily Pretreated Patients with Lower-Risk Myelodysplastic Syndromes and High Transfusion Burden Treated with Imetelstat on the IMerge Phase 3 Trial. Blood 2023, 142: 6479. DOI: 10.1182/blood-2023-181103.Peer-Reviewed Original ResearchLower-risk myelodysplastic syndromesPatient-reported outcomesHigh transfusion burdenTransfusion burdenPlacebo groupMyelodysplastic syndromeTreatment groupsFunctional assessmentCancer Therapy-AnemiaPatient-reported fatigueTransfusion independence rateChronic Illness TherapyPhase 3 trialInferior overall survivalTransfusion-dependent anemiaLeast square meansImprovement of patientsPRO end pointsComposite scorePositive mean changesQuality of lifeFACT-AnTreat populationDyspnea scoreOverall survivalDurable 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 responseImproved 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
Real-World Treatment Patterns and Transfusion Burden Among Newly Diagnosed Older Adults with Acute Myeloid Leukemia
Zeidan A, Cheng W, Kamalakar R, Miller C, Bui C, Montez M, Yee T, Wu Z, Huntington S. Real-World Treatment Patterns and Transfusion Burden Among Newly Diagnosed Older Adults with Acute Myeloid Leukemia. Blood 2022, 140: 3282-3283. DOI: 10.1182/blood-2022-160002.Peer-Reviewed Original Research
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 armsMDS-171: Effects of Luspatercept on Serum Ferritin in Patients with Lower-Risk Myelodysplastic Syndromes (LR-MDS) with Ring Sideroblasts (RS) in the Phase 3 MEDALIST Trial
Fenaux P, Santini V, Mufti G, Diez-Campelo M, Finelli C, Sekeres M, Quesnel B, Beyne-Rauzy O, Garcia-Manero G, Komrokji R, Buckstein R, Voso M, Selleslag D, DeZern A, Greenberg P, Zeidan A, Adès L, Verma A, Savona M, Laadem A, Ito R, Zhang J, Rampersad A, Sinsimer D, Morison J, Louis C, Linde P, Platzbecker U. MDS-171: Effects of Luspatercept on Serum Ferritin 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: s317. DOI: 10.1016/s2152-2650(20)30971-x.Peer-Reviewed Original ResearchBaseline serum ferritinPlacebo-treated patientsLower-risk myelodysplastic syndromesMean serum ferritinSerum ferritinWeek 9Ring sideroblastsRBC transfusion burdenTransfusion reductionTrial patientsPlacebo armTransfusion burdenRBC transfusionTherapy useSignificant morbidityLSM changeMyelodysplastic syndromeIron overloadLuspaterceptWeek 33Ineffective erythropoiesisPatientsBaselinePlaceboFerritinMDS-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