2024
Ziftomenib Combined with Intensive Induction (7+3) in Newly Diagnosed NPM1- m or KMT2A -r Acute Myeloid Leukemia: Interim Phase 1a Results from KOMET-007
Zeidan A, Wang E, Issa G, Erba H, Altman J, Balasubramanian S, Strickland S, Roboz G, Schiller G, McMahon C, Palmisiano N, Madanat Y, Rotta M, Nadiminti K, Wei H, Riches M, Corum D, Leoni M, Dale S, Fathi A. Ziftomenib Combined with Intensive Induction (7+3) in Newly Diagnosed NPM1- m or KMT2A -r Acute Myeloid Leukemia: Interim Phase 1a Results from KOMET-007. Blood 2024, 144: 214-214. DOI: 10.1182/blood-2024-198218.Peer-Reviewed Original ResearchDose-limiting toxicityMinimal residual diseaseAcute myeloid leukemiaMedian time to neutrophil recoveryDays to platelet recoveryMinimal residual disease negativityDecreased neutrophil countKMT2A-rDecreased platelet countNPM1 mutationsAdverse eventsCRC ratesDose levelsNeutrophil recoveryData cutoffQTc prolongationPlatelet recoveryPlatelet countMyeloid leukemiaNeutrophil countDifferentiation syndromeClinical activityCycle 1 day 8Persistent acute myeloid leukemiaStandard dose of cytarabineZiftomenib Combined with Venetoclax/Azacitidine in Relapsed/Refractory NPM1 -m or KMT2A -r Acute Myeloid Leukemia: Interim Phase 1a Results from KOMET-007
Fathi A, Issa G, Wang E, Erba H, Altman J, Balasubramanian S, Roboz G, Schiller G, McMahon C, Palmisiano N, Juckett M, Madanat Y, Rotta M, Pratz K, Yaghmour G, Nadiminti K, Wei H, Riches M, Corum D, Leoni M, Dale S, Zeidan A. Ziftomenib Combined with Venetoclax/Azacitidine in Relapsed/Refractory NPM1 -m or KMT2A -r Acute Myeloid Leukemia: Interim Phase 1a Results from KOMET-007. Blood 2024, 144: 2880-2880. DOI: 10.1182/blood-2024-199170.Peer-Reviewed Original ResearchAcute myeloid leukemiaDecreased neutrophil countDecreased platelet countNPM1 mutationsKMT2A-rAdverse eventsCRC ratesClinical activityR/R patientsData cutoffQTc prolongationPlatelet countMyeloid leukemiaNucleophosmin 1Neutrophil countDifferentiation syndromeComposite complete remission rateCycle 1 day 8R/R acute myeloid leukemiaTreatment-emergent adverse eventsDose of venetoclaxInhibitor-naive patientsDose-escalation cohortsDose-expansion phaseComplete remission rateEffect of Prior Treatments on the Clinical Activity of Imetelstat in Transfusion-Dependent Patients with Erythropoiesis-Stimulating Agent, Relapsed or Refractory/Ineligible Lower-Risk Myelodysplastic Syndromes
Platzbecker U, Santini V, Zeidan A, Sekeres M, Fenaux P, Raza A, Mittelman M, Thépot S, Buckstein R, Germing U, Madanat Y, Diez-Campelo M, Valcarcel D, Jonasova A, Dougherty S, Shah S, Xia Q, Sun L, Navada S, Savona M, Komrokji R. Effect of Prior Treatments on the Clinical Activity of Imetelstat in Transfusion-Dependent Patients with Erythropoiesis-Stimulating Agent, Relapsed or Refractory/Ineligible Lower-Risk Myelodysplastic Syndromes. Blood 2024, 144: 352-352. DOI: 10.1182/blood-2024-203612.Peer-Reviewed Original ResearchLower-risk myelodysplastic syndromesHematological improvement-erythroidErythropoiesis-stimulating agentsErythropoiesis-stimulating agent therapyHb riseRBC-TIHypomethylating agentsTransfusion reductionClinical activityMyelodysplastic syndromeQTc studyRed blood cellsPrior treatmentInternational Working GroupRBC transfusion independenceHypomethylating agent treatmentTransfusion-dependent patientsPhase 2/3 trialsLimited treatment optionsUnited States Food and Drug AdministrationStates Food and Drug AdministrationFirst-in-classFood and Drug AdministrationRBC-TDLenalidomide treatmentClinical activity, pharmacokinetics, and pharmacodynamics of oral hypomethylating agents for myelodysplastic syndromes/neoplasms and acute myeloid leukemia: A multidisciplinary review
Haumschild R, Kennerly-Shah J, Barbarotta L, Zeidan A. Clinical activity, pharmacokinetics, and pharmacodynamics of oral hypomethylating agents for myelodysplastic syndromes/neoplasms and acute myeloid leukemia: A multidisciplinary review. Journal Of Oncology Pharmacy Practice 2024, 30: 721-736. PMID: 38509812, PMCID: PMC11118786, DOI: 10.1177/10781552241238979.Peer-Reviewed Original ResearchOral hypomethylating agentsAcute myeloid leukemiaHypomethylating agentsPK-PD profilesPharmacokinetic (PK)-pharmacodynamicMyeloid leukemiaTreatment selectionPK-PDConcentration-time curveIntravenous (IVImprove treatment outcomesCC-486IV decitabineOral azacitidineMaintenance therapySubcutaneous azacitidineNo significant differenceImprove quality of lifeAzacitidineClinical trialsClinical activityTreatment outcomesDisease settingsDecitabineDisease outcome
2019
Pharmacokinetic Exposure Equivalence and Preliminary Efficacy and Safety from a Randomized Cross over Phase 3 Study (ASCERTAIN study) of an Oral Hypomethylating Agent ASTX727 (cedazuridine/decitabine) Compared to IV Decitabine
Garcia-Manero G, McCloskey J, Griffiths E, Yee K, Zeidan A, Al-Kali A, Dao K, Deeg H, Patel P, Sabloff M, Keating M, Zhu N, Gabrail N, Fazal S, Maly J, Odenike O, Shastri A, DeZern A, O'Connell C, Roboz G, Oganesian A, Hao Y, Keer H, Azab M, Savona M. Pharmacokinetic Exposure Equivalence and Preliminary Efficacy and Safety from a Randomized Cross over Phase 3 Study (ASCERTAIN study) of an Oral Hypomethylating Agent ASTX727 (cedazuridine/decitabine) Compared to IV Decitabine. Blood 2019, 134: 846. DOI: 10.1182/blood-2019-122980.Peer-Reviewed Original ResearchPhase 3 studyFixed-dose combinationClinical trialsHematologic improvementAdverse eventsAstex PharmaceuticalsSpeakers bureauIncyte CorporationSafety findingsComplete responseRandomized crossOtsuka PharmaceuticalClinical activityHypomethylating agentOral fixed-dose combinationCelgene CorporationRandomized phase 3 studyBoehringer IngelheimAdvisory CommitteeSeattle GeneticsDaiichi SankyoClinic visit frequencyComparable clinical activityDifferent myeloid malignanciesPlatelet transfusion dependence
2018
Immunosuppressive therapy in myelodysplastic syndromes: a borrowed therapy in search of the right place
Shallis RM, Chokr N, Stahl M, Pine AB, Zeidan AM. Immunosuppressive therapy in myelodysplastic syndromes: a borrowed therapy in search of the right place. Expert Review Of Hematology 2018, 11: 715-726. PMID: 30024293, DOI: 10.1080/17474086.2018.1503049.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsImmunosuppressive therapyMyelodysplastic syndromeImmune pathwaysManagement of MDSTreatment of MDSClonal hematopoietic stem cell disordersMeaningful clinical activityAdaptive immune pathwaysHematopoietic stem cell disordersStem cell disordersImmune dysregulationDisease coursePeripheral cytopeniasClinical benefitImmune activationTherapeutic optionsAplastic anemiaClinical activityHematologic diseasesCell disordersClinical experienceContinued clarificationLeukemic progressionTherapyPatientsInotuzumab ozogamicin in the treatment of relapsed/refractory acute B cell lymphoblastic leukemia
Uy N, Nadeau M, Stahl M, Zeidan AM. Inotuzumab ozogamicin in the treatment of relapsed/refractory acute B cell lymphoblastic leukemia. Journal Of Blood Medicine 2018, 9: 67-74. PMID: 29713210, PMCID: PMC5908210, DOI: 10.2147/jbm.s136575.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsChemotherapy-based approachesInotuzumab ozogamicinAcute lymphoblastic leukemiaB-ALLLymphoblastic leukemiaChimeric antigen receptor (CAR) T-cell productBispecific T-cell engager blinatumomabAcute B-cell lymphoblastic leukemiaPhiladelphia chromosome-positive diseaseSecond-line salvage therapyB-cell lymphoblastic leukemiaExcellent clinical activityT-cell productsRelapsed B-ALLCD22 monoclonal antibodySalvage therapyAdult patientsSupportive careCell transplantationLeukemic blastsSuperior survivalClinical trialsClinical activityOzogamicinClinical data
2017
Lenalidomide use in myelodysplastic syndromes: Insights into the biologic mechanisms and clinical applications
Stahl M, Zeidan AM. Lenalidomide use in myelodysplastic syndromes: Insights into the biologic mechanisms and clinical applications. Cancer 2017, 123: 1703-1713. PMID: 28192601, DOI: 10.1002/cncr.30585.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsAcute myeloid leukemiaProlong survivalLow-risk MDSLR-MDS patientsEfficacy of lenalidomideImpressive clinical activityRecent clinical dataClonal myeloid neoplasmsMechanism of actionBlood cytopeniasConventional careTransfusion independenceCytogenetic responseClinical activityMyeloid leukemiaClinical dataIneffective hematopoiesisMyeloid neoplasmsDelay progressionHigh riskLenalidomidePatientsVariable riskHeterogeneous groupProgression
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