2023
Treatment Considerations of Myelodysplastic Syndromes/Neoplasms for Pathologists
Madanat Y, Zeidan A. Treatment Considerations of Myelodysplastic Syndromes/Neoplasms for Pathologists. Clinics In Laboratory Medicine 2023, 43: 685-698. PMID: 37865511, DOI: 10.1016/j.cll.2023.07.003.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsBone marrow biopsy reportsAvailable treatment optionsBest therapeutic approachClinical presentationPathologic findingsRisk stratificationTherapeutic optionsTreatment optionsBiopsy reportsDisease entityTherapeutic approachesTreatment considerationsAccurate diagnosisGenetic abnormalitiesDiagnosisDisease subclassificationPatientsNeoplasmsHematopathologistsOptionsPrognosticationAbnormalitiesCliniciansSubclassificationOral 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 malignanciesAdvances in myelodysplastic syndromes: promising novel agents and combination strategies
Madanat Y, Xie Z, Zeidan A. Advances in myelodysplastic syndromes: promising novel agents and combination strategies. Expert Review Of Hematology 2023, 16: 51-63. PMID: 36620919, DOI: 10.1080/17474086.2023.2166923.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsHigh-risk myelodysplastic syndromeMultiple novel agentsMyelodysplastic syndromeNovel agentsClinical trialsTreatment optionsPhase III clinical trialsSelect clinical trialsLow-risk diseaseClonal hematopoietic stem cell neoplasmHigh-risk diseaseBest treatment optionHematopoietic stem cell neoplasmsInnate immune systemStem cell neoplasmMechanism of actionHMA therapyEarly safetyTreatment paradigmEfficacy dataCell neoplasmsDrug combinationsClinical developmentUnmet needImmune system
2022
Venetoclax-based salvage therapy in patients with relapsed/refractory acute myeloid leukemia previously treated with FLT3 or IDH1/2 inhibitors
Bewersdorf JP, Shallis RM, Derkach A, Goldberg AD, Stein A, Stein EM, Marcucci G, Zeidan AM, Shimony S, DeAngelo DJ, Stone RM, Aldoss I, Ball BJ, Stahl M. Venetoclax-based salvage therapy in patients with relapsed/refractory acute myeloid leukemia previously treated with FLT3 or IDH1/2 inhibitors. Leukemia & Lymphoma 2022, 64: 188-196. PMID: 36287540, PMCID: PMC9905301, DOI: 10.1080/10428194.2022.2136952.Peer-Reviewed Original ResearchConceptsAcute myeloid leukemiaSalvage therapyIDH1/2 inhibitorsIDH2 inhibitorsMyeloid leukemiaResponse rateRefractory acute myeloid leukemiaEffective salvage therapyLow-dose cytarabineMedian overall survivalRetrospective cohort studyOverall response rateLow response rateCohort studyOverall survivalAML patientsTreatment optionsFLT3 inhibitorsITD mutationPatientsTherapyFLT3Little dataVenetoclaxInhibitorsEfficacy of FLT3 and IDH1/2 inhibitors in patients with acute myeloid leukemia previously treated with venetoclax
Bewersdorf JP, Shallis RM, Derkach A, Goldberg AD, Stein A, Stein EM, Marcucci G, Zeidan AM, Shimony S, DeAngelo DJ, Stone RM, Aldoss I, Ball BJ, Stahl M. Efficacy of FLT3 and IDH1/2 inhibitors in patients with acute myeloid leukemia previously treated with venetoclax. Leukemia Research 2022, 122: 106942. PMID: 36108424, DOI: 10.1016/j.leukres.2022.106942.Peer-Reviewed Original ResearchConceptsAcute myeloid leukemiaIDH2 inhibitorsMyeloid leukemiaResponse rateRetrospective cohort studyOverall response rateRAS pathway mutationsNovel therapeutic strategiesMedian OSR AMLCohort studyShorter OSLandmark trialsTargeted agentsFrontline treatmentMutant FLT3Combination therapyTreatment optionsIDH1/2 inhibitorsDisease progressionTherapeutic strategiesPatientsSmall molecule inhibitorsVenetoclaxTherapyIn vivo anti-tumor effect of PARP inhibition in IDH1/2 mutant MDS/AML resistant to targeted inhibitors of mutant IDH1/2
Gbyli R, Song Y, Liu W, Gao Y, Biancon G, Chandhok NS, Wang X, Fu X, Patel A, Sundaram R, Tebaldi T, Mamillapalli P, Zeidan AM, Flavell RA, Prebet T, Bindra RS, Halene S. In vivo anti-tumor effect of PARP inhibition in IDH1/2 mutant MDS/AML resistant to targeted inhibitors of mutant IDH1/2. Leukemia 2022, 36: 1313-1323. PMID: 35273342, PMCID: PMC9103411, DOI: 10.1038/s41375-022-01536-x.Peer-Reviewed Original ResearchConceptsAcute myeloid leukemiaMyelodysplastic syndromeMDS/acute myeloid leukemiaRefractory acute myeloid leukemiaPARP inhibitionVivo anti-tumor effectsAlternate therapeutic optionsSubset of AMLAnti-tumor effectsPre-clinical studiesRibose polymerase inhibitorsSerial transplantation assaysHomologous recombination defectsTherapeutic optionsTreatment optionsOverall engraftmentHigh relapseIDH inhibitionMyeloid leukemiaIsocitrate dehydrogenase 1Small molecule inhibitorsCell frequencyXeno-graftsIDH1/2 mutationsMalignant transformation
2021
Analysis of Duration of Response, Exposure-Adjusted Safety and Progression to Acute Myeloid Leukemia (AML) for Patients with Lower-Risk Myelodysplastic Syndromes (LR-MDS) Receiving Luspatercept in the MEDALIST Study
Platzbecker U, Santini V, Komrokji R, Zeidan A, Garcia-Manero G, Buckstein R, Rose S, Fabre S, Miteva D, Zhang J, Yucel A, Hughes C, Fenaux P. Analysis of Duration of Response, Exposure-Adjusted Safety and Progression to Acute Myeloid Leukemia (AML) for Patients with Lower-Risk Myelodysplastic Syndromes (LR-MDS) Receiving Luspatercept in the MEDALIST Study. Blood 2021, 138: 1524. DOI: 10.1182/blood-2021-145723.Peer-Reviewed Original ResearchLower-risk myelodysplastic syndromesTreatment-emergent adverse eventsClinical Trials CommitteeAcute myeloid leukemiaErythropoiesis-stimulating agentsExposure-adjusted incidence ratesRBC-TITrials CommitteeEntire treatment periodDuration of treatmentRing sideroblastsAML progressionCurrent equity holderMedian durationTreatment optionsIncidence rateTreatment periodWk 1Only treatment-emergent adverse eventClass erythroid maturation agentMDS/myeloproliferative neoplasmAdvisory CommitteeRegular RBC transfusionsTolerable safety profileSpeakers bureau
2020
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
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 transfusionsHealth-related quality of life (HRQoL) in patients with untreated higher-risk myelodysplastic syndromes (MDS), acute myeloid leukemia (AML), and chronic myelomonocytic leukemia (CMML) receiving glasdegib + azacitidine (AZA).
Wang E, Bell T, Zeidan A, Bhattacharyya H, Kudla A, Chan G, Sekeres M. Health-related quality of life (HRQoL) in patients with untreated higher-risk myelodysplastic syndromes (MDS), acute myeloid leukemia (AML), and chronic myelomonocytic leukemia (CMML) receiving glasdegib + azacitidine (AZA). Journal Of Clinical Oncology 2020, 38: 7527-7527. DOI: 10.1200/jco.2020.38.15_suppl.7527.Peer-Reviewed Original ResearchChronic myelomonocytic leukemiaAcute myeloid leukemiaMyelodysplastic syndromeIntensive chemotherapyGlobal ImpressionAML cohortAML/myelodysplastic syndromeHigh-risk myelodysplastic syndromeMD Anderson Symptom InventoryFirst-line treatment optionLower symptom burdenPhase Ib studyEnd of treatmentQuality of lifeStudy medicationRemission rateOverall survivalSymptom burdenMDS cohortTreatment optionsMyeloid leukemiaMedian numberMyelomonocytic leukemiaGlasdegibAzacitidineClinical 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
2018
A Multi-center Phase I Trial of Ipilimumab in Patients with Myelodysplastic Syndromes following Hypomethylating Agent Failure
Zeidan AM, Knaus HA, Robinson TM, Towlerton AMH, Warren EH, Zeidner JF, Blackford AL, Duffield AS, Rizzieri D, Frattini MG, Levy YM, Schroeder MA, Ferguson A, Sheldon KE, DeZern AE, Gojo I, Gore SD, Streicher H, Luznik L, Smith BD. A Multi-center Phase I Trial of Ipilimumab in Patients with Myelodysplastic Syndromes following Hypomethylating Agent Failure. Clinical Cancer Research 2018, 24: 3519-3527. PMID: 29716921, PMCID: PMC6680246, DOI: 10.1158/1078-0432.ccr-17-3763.Peer-Reviewed Original ResearchConceptsImmune-related adverse eventsMarrow complete responseMyelodysplastic syndromeGrade 2T cellsHigher immune-related adverse eventsHigh-risk myelodysplastic syndromeT-cell receptor sequencingRisk myelodysplastic syndromesInvestigator-initiated trialClin Cancer ResDrug discontinuationHMA failureStable diseaseSystemic steroidsAdverse eventsMedian survivalComplete responseDismal survivalAdditional patientsClinical benefitTreatment optionsExcessive toxicityPatientsDose levelsAllogeneic Hematopoietic Stem Cell Transplantation Following the Use of Hypomethylating Agents among Patients with Relapsed or Refractory AML: Findings from an International Retrospective Study
Stahl M, DeVeaux M, Montesinos P, Itzykson R, Ritchie EK, Sekeres MA, Majhail N, Barnard J, Podoltsev NA, Brunner AM, Komrokji RS, Bhatt VR, Al-Kali A, Cluzeau T, Santini V, Roboz GJ, Fenaux P, Litzow M, Fathi AT, Perreault S, Kim TK, Prebet T, Vey N, Verma V, Kobbe G, Bergua J, Serrano J, Gore SD, Zeidan AM. Allogeneic Hematopoietic Stem Cell Transplantation Following the Use of Hypomethylating Agents among Patients with Relapsed or Refractory AML: Findings from an International Retrospective Study. Transplantation And Cellular Therapy 2018, 24: 1754-1758. PMID: 29649620, DOI: 10.1016/j.bbmt.2018.03.025.Peer-Reviewed Original ResearchConceptsHematopoietic stem cell transplantationAllogeneic hematopoietic stem cell transplantationHMA therapyStem cell transplantationComplete remissionCell transplantationUnrelated hematopoietic stem cell transplantationInternational retrospective studyLimited treatment optionsAcute myeloid leukemiaChronic GVHDMedian OSPrimary refractoryRR-AMLConditioning regimenRefractory AMLPatients patientsUnrelated donorsEntire cohortPoor prognosisRetrospective studyTreatment optionsMyeloid leukemiaInternational cohortHypomethylating agent
2016
Emerging biological therapies for the treatment of myelodysplastic syndromes
Zeidan AM, Stahl M, Komrokji R. Emerging biological therapies for the treatment of myelodysplastic syndromes. Expert Opinion On Emerging Drugs 2016, 21: 283-300. PMID: 27486848, DOI: 10.1080/14728214.2016.1220534.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsMyelodysplastic syndromeHistone deacetylase inhibitorsTreatment optionsNovel agentsLower-risk myelodysplastic syndromesHigh-risk myelodysplastic syndromeHMA treatment failureRisk-adaptive therapySignificant clinical activityNovel treatment optionsNovel effective therapiesNovel therapeutic approachesHMA failureBiological therapyTreatment failureBone marrow nicheClinical trialsEffective therapyClinical activityImmune responseTherapeutic approachesSurvival advantageFuture therapiesImmune systemDeacetylase inhibitors
2015
The clinical use of DNA methyltransferase inhibitors in myelodysplastic syndromes
Zahr A, Aldin E, Barbarotta L, Podoltsev N, Zeidan AM. The clinical use of DNA methyltransferase inhibitors in myelodysplastic syndromes. Expert Review Of Anticancer Therapy 2015, 15: 1019-1036. PMID: 26292903, DOI: 10.1586/14737140.2015.1061936.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsHigh-risk myelodysplastic syndromeRisk myelodysplastic syndromesMyelodysplastic syndromeDNA methyltransferase inhibitorClinical useAllogeneic hematopoietic cell transplantationHematopoietic cell transplantationAcute myeloid leukemiaMethyltransferase inhibitorFull therapeutic potentialOverall survivalPeripheral cytopeniasCurative treatmentCell transplantationDismal outcomeTreatment optionsMyeloid leukemiaIneffective hematopoiesisOnly interventionTherapeutic potentialHematopoietic malignanciesHeterogeneous groupPatientsSyndromeInhibitorsCase Report of a Patient with Left Ventricular Assistance Device Undergoing Chemotherapy for a New Diagnosis of Lung Cancer
Khan M, Wasim A, Mirrakhimov AE, McMahon BA, Judge DP, Chu LC, Banavali A, Zeidan AM. Case Report of a Patient with Left Ventricular Assistance Device Undergoing Chemotherapy for a New Diagnosis of Lung Cancer. Case Reports In Oncological Medicine 2015, 2015: 163727. PMID: 25874142, PMCID: PMC4385621, DOI: 10.1155/2015/163727.Peer-Reviewed Case Reports and Technical NotesSmall cell lung cancerLimited stage small cell lung cancerModality approachCardiac transplantationHeart failureLung cancerLimited-stage small cell lung cancerLeft ventricular assistance deviceGood organ functionLeft ventricular devicesAdvanced heart failureExcellent performance statusSevere heart failureCell lung cancerVentricular assistance devicePerformance statusTherapeutic dilemmaCardiac supportTreatment optionsCase reportVentricular devicesSevere cardiomyopathyNew diagnosisOrgan functionTherapeutic paradigm
2014
Hepatocellular carcinoma: systemic therapies and future perspectives
Mikhail S, Cosgrove D, Zeidan A. Hepatocellular carcinoma: systemic therapies and future perspectives. Expert Review Of Anticancer Therapy 2014, 14: 1205-1218. PMID: 25199765, DOI: 10.1586/14737140.2014.949246.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsHepatitis C virus infectionC virus infectionIncidence of HCCMedian survival timeCommon primary malignancyCancer-related deathCommon solid cancersFuture therapeutic directionsUnresectable diseaseLiver transplantationLocoregional therapyPrimary malignancySurgical resectionSystemic therapyTreatment optionsSystemic optionsVirus infectionHepatocellular carcinomaSolid cancersSurvival timeMolecular pathogenesisTherapeutic directionsTherapyHCCPatients