2024
Targeted therapies for myelodysplastic syndromes/neoplasms (MDS): current landscape and future directions
Bidikian A, Bewersdorf J, Shallis R, Getz T, Stempel J, Kewan T, Stahl M, Zeidan A. Targeted therapies for myelodysplastic syndromes/neoplasms (MDS): current landscape and future directions. Expert Review Of Anticancer Therapy 2024, 24: 1131-1146. PMID: 39367718, DOI: 10.1080/14737140.2024.2414071.Peer-Reviewed Original ResearchErythropoiesis-stimulating agentsTargeted therapyLR-MDSHR-MDSHypoxia-inducible factorAllogeneic hematopoietic stem cell transplantationLandscape of targeted therapiesHematopoietic stem cell transplantationHeterogeneous group of hematologic malignanciesGroup of hematologic malignanciesMolecular prognostic toolsDuration of responseStem cell transplantationTrial designClinical trial designHypomethylating agentsCell transplantationHematologic malignanciesImprove patient outcomesRNA splicing machineryImmune evasionPrognostic toolTGF-betaTherapyEffective treatmentTreatment of Myelodysplastic Syndromes for Older Patients: Current State of Science, Challenges, and Opportunities
Kewan T, Stahl M, Bewersdorf J, Zeidan A. Treatment of Myelodysplastic Syndromes for Older Patients: Current State of Science, Challenges, and Opportunities. Current Hematologic Malignancy Reports 2024, 19: 138-150. PMID: 38632155, DOI: 10.1007/s11899-024-00733-y.Peer-Reviewed Original ResearchHematopoietic stem cell transplantationAllogeneic hematopoietic stem cell transplantationLower-risk MDSErythropoiesis-stimulating agentsHypomethylating agentsIPSS-MHR-MDSRisk stratificationMolecular International Prognostic Scoring SystemRisk of leukemia progressionTreated with hypomethylating agentsInternational Prognostic Scoring SystemTreatment of myelodysplastic syndromesOral hypomethylating agentsHigh-risk MDSPrognostic Scoring SystemStem cell transplantationEnhanced risk stratificationRecent FindingsRecent advancesRefine treatment strategiesQuality-of-life improvementAssociated with treatmentTreatment decision-makingIntensive chemotherapyMDS patients
2023
Validation of the Molecular International Prognostic Scoring System (IPSS-M) in Patients (Pts) with Myelodysplastic Syndromes/Neoplasms (MDS) Who Were Treated with Hypomethylating Agents (HMA)
Kewan T, Bewersdorf J, Blaha O, Stahl M, Al Ali N, DeZern A, Sekeres M, Carraway H, Desai P, Griffiths E, Stein E, Brunner A, Amaya M, Zeidner J, Savona M, Stempel J, Chandhok N, Logothetis C, Ramaswamy R, Rose A, Roboz G, Rolles B, Wang E, Harris A, Shallis R, Xie Z, Padron E, Maciejewski J, Sallman D, Della Porta M, Komrokji R, Zeidan A. Validation of the Molecular International Prognostic Scoring System (IPSS-M) in Patients (Pts) with Myelodysplastic Syndromes/Neoplasms (MDS) Who Were Treated with Hypomethylating Agents (HMA). Blood 2023, 142: 3240. DOI: 10.1182/blood-2023-186340.Peer-Reviewed Original ResearchComplete remission rateOverall response rateOutcome of ptsMedian overall survivalOverall survivalHypomethylating agentHMA initiationHR-MDSC-indexRisk groupsScoring systemInternational Prognostic Scoring SystemResponse criteriaPrognostic scoring systemHigh-risk diseaseLarge multicenter cohortHigh-risk groupHarrell's C-indexLog-rank testPrediction of outcomeDifferent scoring systemsSubsequent validation studiesHMA cyclesMedian followAllogeneic HSCTLong-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 patientsSafety, Pharmacodynamic, and Anti-Tumor Activity of SL-172154 As Monotherapy and in Combination with Azacitidine (AZA) in Relapsed/Refractory (R/R) Acute Myeloid Leukemia (AML) and Higher-Risk Myelodysplastic Syndromes/Neoplasms (HR-MDS) Patients (pts)
Daver N, Stein A, Bixby D, Chai-Ho W, Zeidner J, Maher K, Stevens D, Stahl M, Yee K, Curran E, Ito S, Sochacki A, Sallman D, Hernandez R, Metenou S, Ma B, Kato K, Zeidan A. Safety, Pharmacodynamic, and Anti-Tumor Activity of SL-172154 As Monotherapy and in Combination with Azacitidine (AZA) in Relapsed/Refractory (R/R) Acute Myeloid Leukemia (AML) and Higher-Risk Myelodysplastic Syndromes/Neoplasms (HR-MDS) Patients (pts). Blood 2023, 142: 4278. DOI: 10.1182/blood-2023-173991.Peer-Reviewed Original ResearchR AMLAcute myeloid leukemiaTreatment-emergent AEsInfusion-related reactionsDose-limiting toxicityDose-escalation cohortsHR-MDSDose-dependent increaseComplete remissionObjective responseAnti-tumor activityBone marrowHypomethylating agentAllo-HCTAML ptsEvaluable ptsEscalation cohortsDose escalationRelapsed/Refractory Acute Myeloid LeukemiaMedian age 70 yearsMorphologic leukemia-free statePhase 1 dose escalationSIRPα-Fc fusion proteinRefractory acute myeloid leukemiaMarrow complete remissionOral therapy for myelodysplastic syndromes/neoplasms and acute myeloid leukemia: a revolution in progress
Venugopal S, Shallis R, Zeidan A. Oral therapy for myelodysplastic syndromes/neoplasms and acute myeloid leukemia: a revolution in progress. Expert Review Of Anticancer Therapy 2023, 23: 903-911. PMID: 37470508, DOI: 10.1080/14737140.2023.2238897.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsAcute myeloid leukemiaOral therapyMyeloid leukemiaAllogeneic hematopoietic stem cell transplantationHematopoietic stem cell transplantationDisease-related complicationsDisease-directed therapyStem cell transplantationQuality of lifeCC-486HR-MDSOral azacitidineClinic visitsMost patientsGood tolerabilityIntensive therapyOptimal regimensCell transplantationTherapy combinationsTreatment optionsMedication administrationPatient outcomesMyeloid neoplasmsClinical developmentMyeloid malignanciesWhy 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 mutationsApprovalInflammation
2020
The Direct Medical Costs of Treatment Discontinuation Among Higher-Risk Myelodysplastic Syndrome Patients Receiving Hypomethylating Agents
Joshi N, Kale H, Corman S, Hill K, Wert T, Zeidan A. The Direct Medical Costs of Treatment Discontinuation Among Higher-Risk Myelodysplastic Syndrome Patients Receiving Hypomethylating Agents. Blood 2020, 136: 17-18. DOI: 10.1182/blood-2020-139642.Peer-Reviewed Original ResearchNon-persistent groupHealthcare resource useDirect medical costsHigh-risk myelodysplastic syndrome (MDS) patientsHR-MDS patientsNon-persistent patientsMyelodysplastic syndrome patientsHMA treatmentCurrent equity holderMedical costsHR-MDSPersistent patientsSyndrome patientsPropensity score-based inverse probabilityContinuous Medicare enrollmentTotal PPPM costsEnd Results-MedicareStem cell transplantRetrospective cohort designHealthcare spendingLoss of responseSubstantial cost burdenHospice care useCurrent employmentER costs
2019
A Randomized, Double-Blind, Placebo-Controlled, Phase II Study of MBG453 Added to Hypomethylating Agents (HMAs) in Patients (pts) with Intermediate, High, or Very High Risk Myelodysplastic Syndrome (MDS): Stimulus-MDS1
Zeidan A, Miyazaki Y, Platzbecker U, Malek K, Niolat J, Kiertsman F, Fenaux P. A Randomized, Double-Blind, Placebo-Controlled, Phase II Study of MBG453 Added to Hypomethylating Agents (HMAs) in Patients (pts) with Intermediate, High, or Very High Risk Myelodysplastic Syndrome (MDS): Stimulus-MDS1. Blood 2019, 134: 4259. DOI: 10.1182/blood-2019-127041.Peer-Reviewed Original ResearchLeukemia-free survivalProgression-free survivalAcute myeloid leukemiaHR-MDSMyelodysplastic syndromeOverall survivalHypomethylating agentTim-3Leukemic stem cellsClinical trialsHigh riskGood safety/tolerability profileInternational Working Group 2006 criteriaSolid tumorsDiagnosis of AMLAllogeneic hematopoietic stem cell transplantationMulticenter phase II clinical trialPrior treatmentAnti-Tim-3 antibodyIPSS-R risk categorySafety/tolerability profileCelgene CorporationTherapy-related myelodysplastic syndromeHigh-risk myelodysplastic syndromeInternational Prognostic Scoring System
2017
Hypomethylating agent (HMA) therapy use and survival in older patients with higher risk myelodysplastic syndromes (HR-MDS) in the United States (USA): A large population-based study.
Zeidan A, Hu X, Long J, Wang R, Huntington S, Podoltsev N, Giri S, Stahl M, Gore S, Ma X, Davidoff A. Hypomethylating agent (HMA) therapy use and survival in older patients with higher risk myelodysplastic syndromes (HR-MDS) in the United States (USA): A large population-based study. Journal Of Clinical Oncology 2017, 35: 7057-7057. DOI: 10.1200/jco.2017.35.15_suppl.7057.Peer-Reviewed Original ResearchOverall survivalHR-MDSDiagnosis yearUS population-based analysisEnd Results-Medicare dataHigh-risk myelodysplastic syndromeLarge population-based studyConventional care regimensMedian overall survivalRetrospective cohort studyRisk myelodysplastic syndromesPopulation-based studyRecent registry dataPopulation-based analysisUse of decitabineAZA-001Unselected natureCohort studyConventional careExcess blastsOlder patientsTherapy usePatient selectionSurvival prolongationCare regimensA phase I trial of ipilimumab (ipi) in patients (pts) with myelodysplastic syndromes (MDS) after hypomethylating agent (HMAs) failure.
Zeidan A, Knaus H, Robinson T, Zeidner J, Blackford A, Rizzieri D, Frattini M, Levy M, Schroeder M, Ferguson A, Sheldon K, Dezern A, Gojo I, Gore S, Streicher H, Luznik L, Duffield A, Smith B. A phase I trial of ipilimumab (ipi) in patients (pts) with myelodysplastic syndromes (MDS) after hypomethylating agent (HMAs) failure. Journal Of Clinical Oncology 2017, 35: 7010-7010. DOI: 10.1200/jco.2017.35.15_suppl.7010.Peer-Reviewed Original ResearchImmune-related adverse eventsOverall survivalMyelodysplastic syndromeHMA failureDose levelsMarrow complete responsePhase 1b studyCTLA-4 blockadeMedian overall survivalImmune checkpoint blockadeKaplan-Meier methodPhase I trialPoor overall survivalExpression of ICOST cell activationDrug discontinuationHR-MDSStable diseaseSystemic steroidsAdverse eventsCheckpoint blockadeClinical responseMaintenance doseObjective responseAllogeneic transplantation
2015
Comparison of risk stratification tools in predicting outcomes of patients with higher-risk myelodysplastic syndromes treated with azanucleosides
Zeidan AM, Sekeres MA, Garcia-Manero G, Steensma DP, Zell K, Barnard J, Ali NA, Zimmerman C, Roboz G, DeZern A, Nazha A, Jabbour E, Kantarjian H, Gore SD, Maciejewski JP, List A, Komrokji R. Comparison of risk stratification tools in predicting outcomes of patients with higher-risk myelodysplastic syndromes treated with azanucleosides. Leukemia 2015, 30: 649-657. PMID: 26464171, PMCID: PMC4775363, DOI: 10.1038/leu.2015.283.Peer-Reviewed Original ResearchConceptsInternational Prognostic Scoring SystemPrognostic scoring systemMD Anderson Prognostic Scoring SystemMyelodysplastic syndromePrognostic toolScoring systemDifferent prognostic scoring systemsHigh-risk myelodysplastic syndromeRelative prognostic performanceOutcomes of patientsFirst-line therapyRisk stratification toolHigh-risk groupWorld Health OrganizationHR-MDSMedian OSObjective responseOverall survivalStandard therapyPrognostic utilityStratification toolPatient cohortPrognostic performancePatientsHealth Organization
2013
The Utility Of Newer Risk Models In Predicting Outcomes Of Patients (pts) With Higher-Risk (HR) Myelodysplastic Syndromes (MDS) Treated With Azactidine (aza)
Zeidan A, Al Ali N, Kharfan-Dabaja M, Padron E, Zhang L, Epling-Burnette P, Lancet J, List A, Komrokji R. The Utility Of Newer Risk Models In Predicting Outcomes Of Patients (pts) With Higher-Risk (HR) Myelodysplastic Syndromes (MDS) Treated With Azactidine (aza). Blood 2013, 122: 2771. DOI: 10.1182/blood.v122.21.2771.2771.Peer-Reviewed Original ResearchMD Anderson Prognostic Scoring SystemMedian overall survivalHigh-risk groupMoffitt Cancer CenterAZA therapyHR-MDSOverall survivalPrognostic scoring systemMyelodysplastic syndromeIntermediate riskRisk groupsLower riskScoring systemPrognostic groupsInt-2Therapy-related myelodysplastic syndromeHigh-risk myelodysplastic syndromeCycles of therapyHR-MDS patientsKaplan-Meier curvesLog-rank testOff-label useAZA initiationRevised IPSSR-IPSSManagement of High-Risk Myelodysplastic Syndrome
Zeidan A, Gore S. Management of High-Risk Myelodysplastic Syndrome. Hematologic Malignancies 2013, 189-210. DOI: 10.1007/978-3-642-36229-3_12.Peer-Reviewed Original ResearchHigh-risk myelodysplastic syndromeHR-MDSDNMTi therapyDNA methyltransferase inhibitorEmergence of resistanceTherapeutic optionsMyelodysplastic syndromeNovel agentsAllogeneic hematopoietic stem cell transplantationCare first-line therapyHematopoietic stem cell transplantationDuration of therapyFirst-line therapyComplex pathogenetic mechanismsStem cell transplantationLimited therapeutic optionsGood responseMechanism of actionAzacitidine therapyStable diseaseHematologic improvementIntensive chemotherapyMaintenance therapyUntreated patientsMedian survival