2024
MDS-156 Efficacy of Imetelstat on Red Blood Cell (RBC)-Transfusion Independence (TI) in the Absence of Platelet Transfusions or Myeloid Growth Factors (MGF) 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. MDS-156 Efficacy of Imetelstat on Red Blood Cell (RBC)-Transfusion Independence (TI) in the Absence of Platelet Transfusions or Myeloid Growth Factors (MGF) in IMerge. Clinical Lymphoma Myeloma & Leukemia 2024, 24: s386. DOI: 10.1016/s2152-2650(24)01344-2.Peer-Reviewed Original ResearchLower-risk myelodysplastic syndromesMyeloid growth factorsErythropoiesis-stimulating agentsRBC-TIPlatelet transfusionsTransfusion-dependentHb levelsLong-term respondersPercentage of patientsHb riseRBC-TDPlacebo patientsNon-del(5qMyelodysplastic syndromePlacebo groupPrimary endpointSecondary endpointsInvestigator's discretionClinical benefitPlaceboAnalysis cutoffImetelstatDisease progressionTransfusionSupportive careMDS-157 Overall Survival (OS), Clinical Benefit, and Durable Red Blood Cell (RBC) Transfusion Independence (TI) With Imetelstat in the IMerge Phase 3 Trial of RBC-Transfusion Dependent (TD) Lower-Risk Myelodysplastic Syndromes (LR-MDS)
Santini V, Komrokji R, Sekeres M, Savona M, Fenaux P, Madanat Y, Oliva E, Buckstein R, Annaášová A, Germing U, Mittelman M, Thepot S, Riggs J, Dougherty S, Berry T, Navada S, Xia Q, Sun L, Zeidan A, Platzbecker U. MDS-157 Overall Survival (OS), Clinical Benefit, and Durable Red Blood Cell (RBC) Transfusion Independence (TI) With Imetelstat in the IMerge Phase 3 Trial of RBC-Transfusion Dependent (TD) Lower-Risk Myelodysplastic Syndromes (LR-MDS). Clinical Lymphoma Myeloma & Leukemia 2024, 24: s386-s387. DOI: 10.1016/s2152-2650(24)01345-4.Peer-Reviewed Original ResearchLower-risk myelodysplastic syndromesNon-del(5q) lower-risk myelodysplastic syndromesErythropoiesis-stimulating agentsRBC-TIOverall survivalRBC-TDNon-del(5qClinical benefitRed blood cellsHemoglobin increaseRBC transfusion dependenceStratified log-rank testMedian follow-upKaplan-Meier methodLog-rank testWithdrawal of consentMedian OSOS ratesHemoglobin riseMyelodysplastic syndromeOS analysisHemoglobin levelsAssess OSPlaceboImetelstatClinical 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, Valcárcel D, Fenaux P, Shortt J, Komrokji R. 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: s192. DOI: 10.1016/s2152-2650(24)00648-7.Peer-Reviewed Original ResearchOverall Survival (OS), Clinical Benefit, and Durable Red Blood Cell (RBC) Transfusion Independence (TI) With Imetelstat in the IMerge Phase 3 Trial of RBC-Transfusion Dependent (TD) Lower-Risk Myelodysplastic Syndromes (LR-MDS)
Santini V, Komrokji R, Sekeres M, Savona M, Fenaux P, Madanat Y, Oliva E, Buckstein R, Jonášová A, Germing U, Mittelman M, Thepot S, Riggs J, Dougherty S, Berry T, Navada S, Xia Q, Sun L, Zeidan A, Platzbecker U. Overall Survival (OS), Clinical Benefit, and Durable Red Blood Cell (RBC) Transfusion Independence (TI) With Imetelstat in the IMerge Phase 3 Trial of RBC-Transfusion Dependent (TD) Lower-Risk Myelodysplastic Syndromes (LR-MDS). Clinical Lymphoma Myeloma & Leukemia 2024, 24: s192. DOI: 10.1016/s2152-2650(24)00647-5.Peer-Reviewed Original ResearchOverall Survival (OS), Clinical Benefit, and Durable Red Blood Cell (RBC) Transfusion Independence (TI) With Imetelstat in the IMerge Phase 3 Trial of RBC-Transfusion Dependent (TD) Lower-Risk Myelodysplastic Syndromes (LR-MDS)
Santini V, Komrokji R, Sekeres M, Savona M, Fenaux P, Madanat Y, Oliva E, Buckstein R, Jonášová A, Germing U, Mittelman M, Thepot S, Riggs J, Dougherty S, Berry T, Navada S, Xia Q, Sun L, Zeidan A, Platzbecker U. Overall Survival (OS), Clinical Benefit, and Durable Red Blood Cell (RBC) Transfusion Independence (TI) With Imetelstat in the IMerge Phase 3 Trial of RBC-Transfusion Dependent (TD) Lower-Risk Myelodysplastic Syndromes (LR-MDS). Clinical Lymphoma Myeloma & Leukemia 2024, 24: s153. DOI: 10.1016/s2152-2650(24)00388-4.Peer-Reviewed Original ResearchEfficacy 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 medianLuspatercept
2023
Impact 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 mutationsLuspatercept 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 mutationsClinical Outcomes in Patients With Refractory Anemia With Excess Blasts (RAEB) Who Receive Hypomethylating Agents (HMAs)
Zeidan A, Mearns E, Ng C, Shah A, Lamarre N, Yellow-Duke A, Alrawashdh N, Yang B, Cheng W, Bui C, Svensson A. Clinical Outcomes in Patients With Refractory Anemia With Excess Blasts (RAEB) Who Receive Hypomethylating Agents (HMAs). Clinical Lymphoma Myeloma & Leukemia 2023, 24: 177-186. PMID: 37996264, DOI: 10.1016/j.clml.2023.10.010.Peer-Reviewed Original ResearchEvent-free survivalAcute myeloid leukemiaMedian overall survivalOverall survivalHypomethylating agentExcess blastsRefractory anemiaReal-world settingMedian event-free survivalFirst-line therapyHematopoietic cell transplantationEligible patientsClinical outcomesCancer RegistryCell transplantationClinical benefitMedicare databaseClinical effectivenessAML progressionClinical trialsPatient outcomesMyeloid leukemiaPatientsOverall populationSignificant differencesConsensus proposal for revised International Working Group 2023 response criteria for higher-risk myelodysplastic syndromes
Zeidan A, Platzbecker U, Bewersdorf J, Stahl M, Adès L, Borate U, Bowen D, Buckstein R, Brunner A, Carraway H, Daver N, Díez-Campelo M, de Witte T, DeZern A, Efficace F, Garcia-Manero G, Garcia J, Germing U, Giagounidis A, Griffiths E, Hasserjian R, Hellström-Lindberg E, Iastrebner M, Komrokji R, Kulasekararaj A, Malcovati L, Miyazaki Y, Odenike O, Santini V, Sanz G, Scheinberg P, Stauder R, van de Loosdrecht A, Wei A, Sekeres M, Fenaux P. Consensus proposal for revised International Working Group 2023 response criteria for higher-risk myelodysplastic syndromes. Blood 2023, 141: 2047-2061. PMID: 36724453, DOI: 10.1182/blood.2022018604.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsHigh-risk MDSComplete remissionResponse criteriaInternational Working GroupClinical trialsHigh-risk myelodysplastic syndromeEnd pointMarrow complete remissionPartial hematologic recoveryClinical end pointsPatient-centered outcomesNovel investigational drugsVariable clinical presentationEvent end pointsHemoglobin thresholdHematologic recoveryCount recoveryClinical presentationClinical benefitMyelodysplastic syndromeIWG criteriaMyelodysplastic neoplasmsConsensus recommendationsInvestigational drugsNew agentsConsiderations for Drug Development in Myelodysplastic Syndromes
Sekeres M, Kim N, DeZern A, Norsworthy K, Garcia J, de Claro R, Theoret M, Jen E, Ehrlich L, Zeidan A, Komrokji R. Considerations for Drug Development in Myelodysplastic Syndromes. Clinical Cancer Research 2023, 29: 2573-2579. PMID: 36688922, PMCID: PMC10349686, DOI: 10.1158/1078-0432.ccr-22-3348.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsMyelodysplastic syndromeTrial designDrug developmentResponse criteriaLow-risk diseaseHigh-risk patientsFuture trial designClinical trial designQuality of lifeValidation of PatientHigh-need populationDurable responsesOverall survivalAnemic patientsTransfusion dependencyClinical benefitPatient populationAdvanced ageClinical trialsDose reductionOutcome instrumentsNew therapiesPreclinical modelingPatientsActive drugImproved 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
A phase 1b study of glasdegib + azacitidine in patients with untreated acute myeloid leukemia and higher-risk myelodysplastic syndromes
Sekeres MA, Schuster M, Joris M, Krauter J, Maertens J, Breems D, Gyan E, Kovacsovics T, Verma A, Vyas P, Wang ES, Ching K, O’Brien T, Gallo Stampino C, Ma WW, Kudla A, Chan G, Zeidan AM. A phase 1b study of glasdegib + azacitidine in patients with untreated acute myeloid leukemia and higher-risk myelodysplastic syndromes. Annals Of Hematology 2022, 101: 1689-1701. PMID: 35488900, DOI: 10.1007/s00277-022-04853-4.Peer-Reviewed Original ResearchConceptsAcute myeloid leukemiaHigh-risk myelodysplastic syndromePhase 1b studyChronic myelomonocytic leukemiaMyelodysplastic syndromeExpansion cohortSafety profileMDS cohortMyeloid leukemiaTreatment-emergent adverse eventsUntreated acute myeloid leukemiaNon-hematologic gradeMedian overall survivalAcceptable safety profileOverall response rateDrug-drug interactionsSafety cohortIntensive chemotherapyAdverse eventsOverall survivalClinical benefitQT prolongationAML cohortMyelomonocytic leukemiaGlasdegib
2020
Comparison of Gilteritinib and Salvage Chemotherapy in FLT3-Mutated Acute Myeloid Leukemia on the Number Needed to Treat for Various Clinical Outcomes: A Secondary Analysis of the Admiral Trial
Pandya B, Qi C, Yang H, Garnham A, Shah M, Zeidan A. Comparison of Gilteritinib and Salvage Chemotherapy in FLT3-Mutated Acute Myeloid Leukemia on the Number Needed to Treat for Various Clinical Outcomes: A Secondary Analysis of the Admiral Trial. Blood 2020, 136: 7. DOI: 10.1182/blood-2020-136184.Peer-Reviewed Original ResearchCR/CRhAcute myeloid leukemiaSalvage chemotherapyADMIRAL trialOverall survivalAML patientsClinical benefitMore patientsSurvival outcomesMyeloid leukemiaAstellas PharmaComplete remission/complete remissionConfidence intervalsTyrosine kinase 3 mutationsLonger median overall survivalDismal survival outcomesIncomplete hematologic recoveryIncomplete platelet recoveryMedian overall survivalSuperior clinical benefitSignificant clinical benefitAbsolute rate differenceSelective FLT3 inhibitorHigh response rateEvent rate differenceEfficacy 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 armsClinical 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 differencesClinical 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