2023
Why 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
2022
A Phase 1/2 Study of the Oral Janus Kinase 1 Inhibitors INCB052793 and Itacitinib Alone or in Combination With Standard Therapies for Advanced Hematologic Malignancies
Zeidan AM, Cook RJ, Bordoni R, Berenson JR, Edenfield WJ, Mohan S, Zhou G, Asatiani E, Srinivas N, Savona MR. A Phase 1/2 Study of the Oral Janus Kinase 1 Inhibitors INCB052793 and Itacitinib Alone or in Combination With Standard Therapies for Advanced Hematologic Malignancies. Clinical Lymphoma Myeloma & Leukemia 2022, 22: 523-534. PMID: 35260349, DOI: 10.1016/j.clml.2022.01.012.Peer-Reviewed Original ResearchConceptsAcute myeloid leukemiaPhase 1/2 studyAdvanced hematologic malignanciesMyelodysplastic syndromeHematologic malignanciesObjective responseStandard therapyRefractory acute myeloid leukemiaPhase 2 doseObjective response rateRefractory multiple myelomaPhase 2Lack of efficacyInhibition of JAK1Janus kinasePhase 1Primary endpointTreatment discontinuationAdverse eventsProgressive diseaseDose escalationStudy treatmentMultiple myelomaMyeloid leukemiaDNA methyltransferase inhibitor
2021
Efficacy of Oral Decitabine/Cedazuridine (ASTX727) in the CMML Subgroup from the Ascertain Phase 3 Study
Savona M, McCloskey J, Griffiths E, Yee K, Zeidan A, Al-Kali A, Deeg H, Patel P, Sabloff M, Keating M, Dao K, Zhu N, Gabrail N, Fazal S, Maly J, Odenike O, Kantarjian H, DeZern A, O'Connell C, Roboz G, Busque L, Wells R, Amin H, Randhawa J, Leber B, Hao Y, Keer H, Azab M, Garcia-Manero G. Efficacy of Oral Decitabine/Cedazuridine (ASTX727) in the CMML Subgroup from the Ascertain Phase 3 Study. Blood 2021, 138: 3682. PMCID: PMC8701430, DOI: 10.1182/blood-2021-154179.Peer-Reviewed Original ResearchChronic myelomonocytic leukemiaMedian overall survivalAdverse eventsComplete responseOverall survivalMyelodysplastic syndromeDNA methyltransferase inhibitorTreatment of CMMLDiagnosis of CMMLTreatment-emergent adverse eventsRandomized cross-over studyMarrow complete responseCommon Terminology CriteriaCycles of therapyIntermediate-risk cytogeneticsMDS/MPN overlap syndromesOlder cancer patientsCTCAE grade 3Subpopulation of patientsCross-over studyStandard of careEntire study populationPandemic SARS-CoV-2SARS-CoV-2Intra-patient comparisonOral Decitabine/Cedazuridine in Patients with Lower Risk Myelodysplastic Syndrome: A Longer-Term Follow-up of from the Ascertain Study
Garcia-Manero G, McCloskey J, Griffiths E, Yee K, Zeidan A, Al-Kali A, Deeg H, Patel P, Sabloff M, Keating M, Dao K, Zhu N, Gabrail N, Fazal S, Maly J, Odenike O, Kantarjian H, DeZern A, O'Connell C, Roboz G, Busque L, Wells R, Amin H, Randhawa J, Leber B, Hao Y, Keer H, Azab M, Savona M. Oral Decitabine/Cedazuridine in Patients with Lower Risk Myelodysplastic Syndrome: A Longer-Term Follow-up of from the Ascertain Study. Blood 2021, 138: 66. PMCID: PMC8701611, DOI: 10.1182/blood-2021-144648.Peer-Reviewed Original ResearchLower-risk myelodysplastic syndromesClinical Trials CommitteeMedian leukemia-free survivalMedian overall survivalRisk myelodysplastic syndromesBristol-Myers SquibbMyelodysplastic syndromeTransfusion independenceTrials CommitteeOral DECDNA methyltransferase inhibitorOverall survivalComplete responseAstex PharmaceuticalsSpeakers bureauCC-486Hematologic improvementDaiichi SankyoTreatment-emergent adverse eventsHigh-risk MDS patientsAllogeneic stem cell transplantSARS-CoV-2 infectionAdvisory CommitteeRandomized cross-over studyPandemic SARS-CoV-2 infection
2020
Clinical Efficacy and Safety of Oral Decitabine/Cedazuridine in 133 Patients with Myelodysplastic Syndromes (MDS) and Chronic Myelomonocytic Leukemia (CMML)
Savona M, McCloskey J, Griffiths E, Yee K, Al-Kali A, Zeidan A, Deeg H, Patel P, Sabloff M, Keating M, Dao K, Zhu N, Gabrail N, Fazal S, Maly J, Odenike O, Kantarjian H, DeZern A, O'Connell C, Roboz G, Busque L, Wells R, Amin H, Randhawa J, Leber B, Hao Y, Keer H, Azab M, Garcia-Manero G. Clinical Efficacy and Safety of Oral Decitabine/Cedazuridine in 133 Patients with Myelodysplastic Syndromes (MDS) and Chronic Myelomonocytic Leukemia (CMML). Blood 2020, 136: 37-38. PMCID: PMC8330281, DOI: 10.1182/blood-2020-133855.Peer-Reviewed Original ResearchChronic myelomonocytic leukemiaRed blood cellsMyelodysplastic syndromeComplete responseHematological improvementAdverse eventsAstex PharmaceuticalsHypomethylating agentConsecutive weeksSpeakers bureauMedian durationClinical efficacyDaiichi SankyoDNA methyltransferase inhibitorCommon treatment-emergent adverse eventsAllogeneic hematopoietic cell transplantTreatment-emergent adverse eventsTreatment of MDSBoehringer IngelheimAdvisory CommitteeRandomized cross-over studySeattle GeneticsDose combination drugsOral hypomethylating agentOverall objective response
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 groupPatientsSyndromeInhibitorsEpigenetic Therapy in Acute Myeloid Leukemia: Current and Future Directions
Kim TK, Gore SD, Zeidan AM. Epigenetic Therapy in Acute Myeloid Leukemia: Current and Future Directions. Seminars In Hematology 2015, 52: 172-183. PMID: 26111464, PMCID: PMC5785931, DOI: 10.1053/j.seminhematol.2015.04.003.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsAcute myeloid leukemiaMyeloid leukemiaTreatment of AMLPathogenesis of AMLDevelopment of AMLNormal physiologic developmentHistone deacetylase inhibitorsEpigenetic therapyDNA methylationHistone methylation/acetylationTherapeutic optionsClinical evaluationDNA methyltransferase inhibitorHistone tail modificationsInhibitor of histoneMethylation/acetylationPromising drugClinical practiceTherapeutic targetingMutant isocitrate dehydrogenasesDeacetylase inhibitorsActual DNA sequenceAberrant DNA methylationPhysiologic developmentImportant mechanism
2013
Management 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