2023
Luspatercept Modulates Inflammation in the Bone Marrow, Restores Effective Erythropoiesis/Hematopoiesis, and Provides Sustained Clinical Benefit Versus Epoetin Alfa (EA): Biomarker Analysis from the Phase 3 COMMANDS Study
Hayati S, Zeidan A, Garcia-Manero G, Platzbecker U, Ahsan A, Verma A, Aluri S, Guerrero M, Gandhi A, Suragani R, Vodala S. Luspatercept Modulates Inflammation in the Bone Marrow, Restores Effective Erythropoiesis/Hematopoiesis, and Provides Sustained Clinical Benefit Versus Epoetin Alfa (EA): Biomarker Analysis from the Phase 3 COMMANDS Study. Blood 2023, 142: 1845. DOI: 10.1182/blood-2023-178674.Peer-Reviewed Original ResearchBM mononuclear cellsLow-risk MDSEpoetin alfaWk 48Myelodysplastic syndromeWk 24Clinical benefitPg/Bone marrowErythroid precursorsITT populationIL-1Ring sideroblastsN-terminal pro-brain natriuretic peptideLower-risk myelodysplastic syndromesPro-brain natriuretic peptideHematopoietic stem cellsDysplastic erythroid precursorsRBC transfusion independencePhase 3 trialSuperior clinical benefitSerum cytokine analysisAnti-inflammatory signalingIL-10 signalingComplete blood countImpact 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 mutationsLong-term utilization and benefit of luspatercept in transfusion-dependent, erythropoiesis-stimulating agent-refractory or -intolerant patients with lower-risk myelodysplastic syndromes with ring sideroblasts
Platzbecker U, Santini V, Komrokji R, Zeidan A, Garcia-Manero G, Buckstein R, Miteva D, Keeperman K, Holot N, Nadal J, Lai Y, Vodala S, Rosettani B, Giuseppi A, Yucel A, Fenaux P. Long-term utilization and benefit of luspatercept in transfusion-dependent, erythropoiesis-stimulating agent-refractory or -intolerant patients with lower-risk myelodysplastic syndromes with ring sideroblasts. Leukemia 2023, 37: 2314-2318. PMID: 37752285, PMCID: PMC10624606, DOI: 10.1038/s41375-023-02031-7.Peer-Reviewed Original ResearchWhy 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 mutationsApprovalInflammationImproved 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
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 minorityTherapyTransfusionMyelodysplasiaSideroblastsSyndromeTrialsWeeksMonths
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 bureau
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-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 increaseMDS-280: Longer-Term RBC Transfusion Reduction in the Phase 3 MEDALIST Study of Luspatercept in Patients with Lower-Risk MDS (LR-MDS) with Ring Sideroblasts (RS)
Komrokji R, Sekeres M, Zeidan A, Fenaux P, Platzbecker U, DeZern A, Greenberg P, Savona M, Jurcic J, Verma A, Mufti G, Buckstein R, Santini V, Laadem A, Ito R, Zhang J, Louis C, Linde P, Garcia-Manero G. MDS-280: Longer-Term RBC Transfusion Reduction in the Phase 3 MEDALIST Study of Luspatercept in Patients with Lower-Risk MDS (LR-MDS) with Ring Sideroblasts (RS). Clinical Lymphoma Myeloma & Leukemia 2020, 20: s322. DOI: 10.1016/s2152-2650(20)30979-4.Peer-Reviewed Original ResearchLonger-term RBC transfusion reduction in the phase III MEDALIST study of luspatercept in patients (pts) with lower-risk MDS with ring sideroblasts (RS).
Komrokji R, Sekeres M, Zeidan A, Fenaux P, List A, Dezern A, Greenberg P, Savona M, Jurcic J, Verma A, Mufti G, Buckstein R, Santini V, Laadem A, Ito R, Zhang J, Louis C, Linde P, Garcia-Manero G. Longer-term RBC transfusion reduction in the phase III MEDALIST study of luspatercept in patients (pts) with lower-risk MDS with ring sideroblasts (RS). Journal Of Clinical Oncology 2020, 38: 7518-7518. DOI: 10.1200/jco.2020.38.15_suppl.7518.Peer-Reviewed Original ResearchLow-risk MDSPBO armRing sideroblastsWeek 1Transfusion visitRBC transfusionSerum ferritinWeek 33Week 9Mean numberClass erythroid maturation agentRBC unitsBurden reductionPhase 3 trialLower-risk MDSErythroid maturation agentTransfusion reductionMaturation agentsTransfusion eventsClinical efficacyL vsLuspaterceptResponse episodesWeeksTransfusionClinical 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
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 transfusionClinical Effectiveness of Hypomethylating Agents (HMAs) and Lenalidomide (Len) in Older Patients (pts) with Refractory Anemia with Ring Sideroblasts: A Large Population-Based Study in the United States (US)
Wang X, Wang R, Zhang C, Zeidan A, Podoltsev N, Huntington S, Gore S, Davidoff A, Ma X. Clinical Effectiveness of Hypomethylating Agents (HMAs) and Lenalidomide (Len) in Older Patients (pts) with Refractory Anemia with Ring Sideroblasts: A Large Population-Based Study in the United States (US). Blood 2019, 134: 4748. DOI: 10.1182/blood-2019-128821.Peer-Reviewed Original ResearchPopulation-based studyLR-MDSMedian overall survivalOverall survivalClinical effectivenessHypomethylating agentCelgene CorporationMedian durationRed blood cellsMedian timeRing sideroblastsBoehringer IngelheimAdvisory CommitteeLarge population-based studyDaiichi SankyoOlder adultsAbnormal erythroid precursorsTransfusion independence rateEnd Results-MedicareHigh-risk MDSErythropoiesis-stimulating agentsKaplan-Meier statisticsComparative clinical effectivenessEnd of studyPart D coverage
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