2024
Beyond HMAs: Novel targets and therapeutic approaches
Getz T, Bewersdorf J, Kewan T, Stempel J, Bidikian A, Shallis R, Stahl M, Zeidan A. Beyond HMAs: Novel targets and therapeutic approaches. Seminars In Hematology 2024 PMID: 39389839, DOI: 10.1053/j.seminhematol.2024.08.001.Peer-Reviewed Original ResearchAcute myeloid leukemiaDelays progression to acute myeloid leukemiaHeterogeneous group of clonal hematopoietic disordersGroup of clonal hematopoietic disordersMolecular International Prognostic Scoring SystemRandomized phase 3 clinical trialProgression to acute myeloid leukemiaInternational Prognostic Scoring SystemLower-risk MDS patientsRisk stratification of patientsPhase 3 clinical trialsCombination of azacitidineHypomethylating agent combinationsCurrent treatment landscapeFirst line therapyPrognostic Scoring SystemBiomarker-directed therapiesClonal hematopoietic disordersLack of therapeutic agentsStratification of patientsEarly phase trialsErythropoiesis stimulating agentsTreated with therapiesVariable clinical featuresStandard of careEfficacy 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 progressionCLO24-079: Results From Phase 3 Trial of Imetelstat, a First-in-Class Telomerase Inhibitor, in Patients With Red Blood Cell Transfusion Dependent (RBC-TD) Non-del(5q) Lower-Risk Myelodysplastic Syndromes (LR-MDS) Relapsed/Refractory to/Ineligible for Erythropoiesis Stimulating Agents (ESAs)
Madanat Y, Savona M, Sekeres M, Platzbecker U, Santini V, Fenaux P, Diez-Campelo M, Valcárcel D, Berry T, Dougherty S, Shah S, Sun L, Wan Y, Huang F, Navada S, Komrokji R, Zeidan A. CLO24-079: Results From Phase 3 Trial of Imetelstat, a First-in-Class Telomerase Inhibitor, in Patients With Red Blood Cell Transfusion Dependent (RBC-TD) Non-del(5q) Lower-Risk Myelodysplastic Syndromes (LR-MDS) Relapsed/Refractory to/Ineligible for Erythropoiesis Stimulating Agents (ESAs). Journal Of The National Comprehensive Cancer Network 2024, 22 DOI: 10.6004/jnccn.2023.7228.Peer-Reviewed Original Research
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 patientsDurable 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 responsePatient-Reported Outcomes (PRO) of Luspatercept Versus Epoetin Alfa in Erythropoiesis-Stimulating Agent (ESA)-Naïve, Transfusion-Dependent (TD), Lower-Risk Myelodysplastic Syndromes (LR-MDS): Results from the Phase 3 COMMANDS Study
Oliva E, Platzbecker U, Della Porta M, Garcia-Manero G, Santini V, Fenaux P, Shortt J, Komrokji R, Pelligra C, Guo S, Lord-Bessen J, Xiao H, Yucel A, Miteva D, Rose S, Kreitz S, Sekeres M, Zeidan A. Patient-Reported Outcomes (PRO) of Luspatercept Versus Epoetin Alfa in Erythropoiesis-Stimulating Agent (ESA)-Naïve, Transfusion-Dependent (TD), Lower-Risk Myelodysplastic Syndromes (LR-MDS): Results from the Phase 3 COMMANDS Study. Blood 2023, 142: 4596. DOI: 10.1182/blood-2023-174660.Peer-Reviewed Original ResearchLower-risk myelodysplastic syndromesEORTC QLQ-C30Patient-reported outcomesErythropoietin-stimulating agentsEpoetin alfaQLQ-C30FACT-AnSustained improvementTreatment armsESA-naïveTransfusion-DependentTreatment tolerabilityStratified Cox proportional hazards regression modelDay 1Cox proportional hazards regression modelCancer Therapy-Anemia (FACT-An) questionnaireLife Questionnaire Core 30Proportional hazards regression modelsMajority of patientsTreatment side effectsPost-baseline visitTransfusion-dependent patientsErythropoiesis stimulating agentsHazards regression modelsPhase 3
2017
Management of myelofibrosis: JAK inhibition and beyond
Stahl M, Zeidan AM. Management of myelofibrosis: JAK inhibition and beyond. Expert Review Of Hematology 2017, 10: 459-477. PMID: 28395559, DOI: 10.1080/17474086.2017.1317590.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsBone marrow fibrosisMarrow fibrosisAbnormal cytokine expressionClinical trial evidenceJAK2 V617F allele burdenErythropoiesis stimulating agentsNovel therapeutic optionsAnti-fibrosis agentsV617F allele burdenJAK2 inhibitor ruxolitinibNovel therapeutic agentsJAK2 V617F mutationConstitutional symptomsCytoreductive drugsSymptom burdenImmunomodulatory drugsSurvival improvementJAK1/2 inhibitorMF patientsTherapeutic optionsTrial evidenceCytokine expressionExtramedullary hematopoiesisPrognostic assessmentRuxolitinib monotherapyManagement of lower-risk myelodysplastic syndromes without del5q: current approach and future trends
Stahl M, Zeidan AM. Management of lower-risk myelodysplastic syndromes without del5q: current approach and future trends. Expert Review Of Hematology 2017, 10: 345-364. PMID: 28277851, DOI: 10.1080/17474086.2017.1297704.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsErythropoiesis stimulating agentsMyelodysplastic syndromeLR-MDSImmunosuppressive therapyTreatment modalitiesLower-risk myelodysplastic syndromesTGF-β pathway inhibitorCombination treatment modalitiesLR-MDS patientsPromising investigational agentsSubset of patientsAvailable therapeutic modalitiesGoals of careStandard therapeutic optionPredictors of responseCurrent treatment modalitiesAcute myeloid leukemiaQuality of lifeBone marrow failureRisk assessment toolSymptom controlBlood cytopeniasInvestigational agentsTherapeutic optionsClinical behavior
2015
Patient Cost Sharing and Receipt of Erythropoiesis-Stimulating Agents Through Medicare Part D
Davidoff AJ, Hendrick FB, Zeidan AM, Baer MR, Stuart BC, Shenolikar RA, Gore SD. Patient Cost Sharing and Receipt of Erythropoiesis-Stimulating Agents Through Medicare Part D. JCO Oncology Practice 2015, 11: e190-e198. PMID: 25563701, PMCID: PMC4371123, DOI: 10.1200/jop.2014.001527.Peer-Reviewed Original ResearchConceptsErythropoiesis-stimulating agentsLow-income subsidyMyelodysplastic syndromePhysician's officePart DOOP paymentsErythropoiesis stimulating agentsPart D claimsMedicare Part APatient cost sharingMedicare Part DESA useAnemia managementD claimsInjected medicationsDiagnosis codesMultivariable modelHome injectionMedicare beneficiariesPart BPatientsPocket costsPatient accessPrescription benefitsCost sharing
2012
Association Between FDA Safety Warnings, CMS Coverage Restrictions and Adherence to Guidelines for ESA Use in Patients with Myelodysplastic Syndromes
Hendrick F, Davidoff A, Zeidan A, Gore S, Baer M. Association Between FDA Safety Warnings, CMS Coverage Restrictions and Adherence to Guidelines for ESA Use in Patients with Myelodysplastic Syndromes. Blood 2012, 120: 971. DOI: 10.1182/blood.v120.21.971.971.Peer-Reviewed Original ResearchErythropoiesis stimulating agentsCMS national coverage determinationsFDA safety warningsESA useNational Coverage DeterminationMyelodysplastic syndromeESA initiationSerum EPO levelsMDS patientsUse of ESAsEPO levelsChronic renal failureOff-label indicationsProportion of patientsChemotherapy-related anemiaSpecific clinical parametersOff-label useTreatment of anemiaEnd of studySerum erythropoietin levelsLikelihood of responseLogistic regression modelsThromboembolic eventsTransfusion useAdverse eventsMedicare Prescription Drug Coverage and Home Use of Erythropoiesis-Stimulating Agents for MDS-Associated Anemia: A Medicare-Database Analysis.
Davidoff A, Hendrick F, Stuart B, Zeidan A, Shenolikar R, Gore S, Baer M. Medicare Prescription Drug Coverage and Home Use of Erythropoiesis-Stimulating Agents for MDS-Associated Anemia: A Medicare-Database Analysis. Blood 2012, 120: 3176. DOI: 10.1182/blood.v120.21.3176.3176.Peer-Reviewed Original ResearchErythropoiesis stimulating agentsLow-income subsidyPart D claimsMyelodysplastic syndromePart D plansPrior authorizationStudy cohortD claimsOOP paymentsMDS diagnosisPart DUse of ESAsPart D.Lower-risk myelodysplastic syndromesPoor functional statusChronic renal failureD plansErythropoiesis-stimulating agentsMultivariate logistic regressionTreatment of anemiaPart D coverageMedicare Part APlan characteristicsPrescription drug coveragePatient-level observations