2024
Luspatercept versus epoetin alfa in erythropoiesis-stimulating agent-naive, transfusion-dependent, lower-risk myelodysplastic syndromes (COMMANDS): primary analysis of a phase 3, open-label, randomised, controlled trial
Della Porta M, Garcia-Manero G, Santini V, Zeidan A, Komrokji R, Shortt J, Valcárcel D, Jonasova A, Dimicoli-Salazar S, Tiong I, Lin C, Li J, Zhang J, Pilot R, Kreitz S, Pozharskaya V, Keeperman K, Rose S, Prebet T, Lai Y, Degulys A, Paolini S, Cluzeau T, Fenaux P, Platzbecker U. Luspatercept versus epoetin alfa in erythropoiesis-stimulating agent-naive, transfusion-dependent, lower-risk myelodysplastic syndromes (COMMANDS): primary analysis of a phase 3, open-label, randomised, controlled trial. The Lancet Haematology 2024, 11: e646-e658. PMID: 39038479, DOI: 10.1016/s2352-3026(24)00203-5.Peer-Reviewed Original ResearchLower-risk myelodysplastic syndromesRed blood cell transfusion independenceTreatment-emergent adverse eventsMedian follow-upEpoetin alfa groupMyelodysplastic syndromeLuspatercept groupTransfusion-dependentSerum erythropoietin concentrationPrimary endpointEpoetin alfaTransfusion independenceOpen-labelAlfa groupAdverse eventsFollow-upRed blood cell transfusion burdenErythropoietin concentrationIntention-to-treat populationControlled trialsCommon grade 3Epoetin alfa recipientsMean haemoglobin increasePrimary analysisProportion of patientsClinical 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 patientsImpact 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 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 leukemiaImproved 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
2021
Phase 3 VERONA study of venetoclax with azacitidine to assess change in complete remission and overall survival in treatment-naïve higher-risk myelodysplastic syndromes.
Zeidan A, Garcia J, Fenaux P, Platzbecker U, Miyazaki Y, Xiao Z, Zhou Y, Naqvi K, Kye S, Garcia-Manero G. Phase 3 VERONA study of venetoclax with azacitidine to assess change in complete remission and overall survival in treatment-naïve higher-risk myelodysplastic syndromes. Journal Of Clinical Oncology 2021, 39: tps7054-tps7054. DOI: 10.1200/jco.2021.39.15_suppl.tps7054.Peer-Reviewed Original ResearchHematopoietic stem cell transplantOverall survivalAcute myeloid leukemiaCR rateComplete remissionTransfusion independenceCell transplantationDisease progressionMyeloid leukemiaDay 1B-cell lymphoma-2 inhibitorRed blood cell transfusion independenceHigh-risk myelodysplastic syndromeAllogenic stem cell transplantationCo-morbid patientsIWG 2006 criteriaPhase 1b studyPlatelet transfusion independenceMedian overall survivalFirst-line treatmentPhase 3 studyBone marrow blastsDe novo patientsHematopoietic cell transplantationStudy days 1
2020
Clinical outcomes of older patients with AML receiving hypomethylating agents: a large population-based study in the United States
Zeidan AM, Wang R, Wang X, Shallis RM, Podoltsev NA, Bewersdorf JP, Huntington SF, Neparidze N, Giri S, Gore SD, Davidoff AJ, Ma X. Clinical outcomes of older patients with AML receiving hypomethylating agents: a large population-based study in the United States. Blood Advances 2020, 4: 2192-2201. PMID: 32433746, PMCID: PMC7252544, DOI: 10.1182/bloodadvances.2020001779.Peer-Reviewed Original ResearchConceptsAcute myeloid leukemiaDecitabine-treated patientsTransfusion independenceRed blood cell transfusion independenceLarge population-based studyOlder AML patientsRBC transfusion independenceEnd Results-MedicarePopulation-based studyStandard of careAgent azacitidineMedian survivalOlder patientsIntensive therapyAML patientsClinical outcomesClinical benefitMyeloid leukemiaMortality riskPatientsAzacitidineDecitabineOlder adultsOne-thirdMeaningful differences
2018
The use of immunosuppressive therapy in MDS: clinical outcomes and their predictors in a large international patient cohort
Stahl M, DeVeaux M, de Witte T, Neukirchen J, Sekeres MA, Brunner AM, Roboz GJ, Steensma DP, Bhatt VR, Platzbecker U, Cluzeau T, Prata PH, Itzykson R, Fenaux P, Fathi AT, Smith A, Germing U, Ritchie EK, Verma V, Nazha A, Maciejewski JP, Podoltsev NA, Prebet T, Santini V, Gore SD, Komrokji RS, Zeidan AM. The use of immunosuppressive therapy in MDS: clinical outcomes and their predictors in a large international patient cohort. Blood Advances 2018, 2: 1765-1772. PMID: 30037803, PMCID: PMC6058241, DOI: 10.1182/bloodadvances.2018019414.Peer-Reviewed Original ResearchConceptsAnti-thymocyte globulinRBC transfusion independenceImmunosuppressive therapyTransfusion independenceOverall response rateHypocellular bone marrowMyelodysplastic syndromeOverall survivalBone marrowRed blood cell transfusion independenceHorse anti-thymocyte globulinRabbit anti-thymocyte globulinInternational Working Group criteriaCox proportional hazards modelSingle-center natureMedian overall survivalKaplan-Meier methodLarge international cohortLarge international patient cohortProportional hazards modelInternational patient cohortPredictors of benefitParoxysmal nocturnal hemoglobinuriaLogistic regression modelsSteroid monotherapy