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 therapyCharacterization 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 activityDurable 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
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 erythropoiesisPatientsBaselinePlaceboFerritinClinical 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