2021
Venetoclax and Azacitidine in the Treatment of Patients with Relapsed/Refractory Myelodysplastic Syndrome
Zeidan A, Borate U, Pollyea D, Brunner A, Roncolato F, Garcia J, Filshie R, Odenike O, Watson A, Krishnadasan R, Bajel A, Naqvi K, Zha J, Hogdal L, Zhou Y, Hoffman D, Kye S, Garcia-Manero G. Venetoclax and Azacitidine in the Treatment of Patients with Relapsed/Refractory Myelodysplastic Syndrome. Blood 2021, 138: 537. DOI: 10.1182/blood-2021-145646.Peer-Reviewed Original ResearchClinical Trials CommitteeHigh-risk myelodysplastic syndromeMedian overall survivalAdverse eventsMyelodysplastic syndromeTrials CommitteeOverall survivalMedian timeClinical trialsFebrile neutropeniaPrior therapyComplete remissionTransfusion independenceClinical outcomesBcl-2 inhibitorsMyeloid leukemiaEastern Cooperative Oncology Group performance statusGrade treatment-emergent adverse eventsInternational Working Group 2006 criteriaOverall median progression-free survivalIncomplete blood count recoveryMedian progression-free survivalOral BCL-2 inhibitorTreatment-emergent adverse eventsAllogeneic hematopoietic stem cells
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 SystemAssessment of Longer-Term Efficacy and Safety in the Phase 3, Randomized, Double-Blind, Placebo-Controlled MEDALIST Trial of Luspatercept to Treat Anemia in Patients (Pts) with Revised International Prognostic Scoring System (IPSS-R) Very Low-, Low-, or Intermediate-Risk Myelodysplastic Syndromes (MDS) with Ring Sideroblasts (RS) Who Require Red Blood Cell (RBC) Transfusions
Fenaux P, Mufti G, Buckstein R, Santini V, Díez-Campelo M, Finelli C, Cazzola M, Ilhan O, Sekeres M, Komrokji R, List A, Zeidan A, Verma A, Laadem A, Ito R, Zhang J, Rampersad A, Sinsimer D, Linde P, Garcia-Manero G, Platzbecker U. Assessment of Longer-Term Efficacy and Safety in the Phase 3, Randomized, Double-Blind, Placebo-Controlled MEDALIST Trial of Luspatercept to Treat Anemia in Patients (Pts) with Revised International Prognostic Scoring System (IPSS-R) Very Low-, Low-, or Intermediate-Risk Myelodysplastic Syndromes (MDS) with Ring Sideroblasts (RS) Who Require Red Blood Cell (RBC) Transfusions. Blood 2019, 134: 841. DOI: 10.1182/blood-2019-123064.Peer-Reviewed Original ResearchErythropoiesis-stimulating agentsIntermediate-risk myelodysplastic syndromesRBC-TIClinical benefitMyelodysplastic syndromeData cutoffHighest dose levelTransfusion burdenCelgene CorporationRing sideroblastsSpeakers bureauMedian durationDose levelsInternational Working Group 2006 criteriaClass erythroid maturation agentGrade 1Red blood cell transfusionInternational Prognostic Scoring SystemLower-risk myelodysplastic syndromesAdvisory CommitteeLow-risk MDSRBC transfusion independenceRegular RBC transfusionsMedian treatment durationBlood cell transfusionA Phase 1b Study Evaluating the Safety and Efficacy of Venetoclax As Monotherapy or in Combination with Azacitidine for the Treatment of Relapsed/Refractory Myelodysplastic Syndrome
Zeidan A, Pollyea D, Garcia J, Brunner A, Roncolato F, Borate U, Odenike O, Bajel A, Watson A, Götze K, Nolte F, Tan P, Hong W, Dunbar M, Zhou Y, Gressick L, Ainsworth W, Harb J, Salem A, Hayslip J, Swords R, Garcia-Manero G. A Phase 1b Study Evaluating the Safety and Efficacy of Venetoclax As Monotherapy or in Combination with Azacitidine for the Treatment of Relapsed/Refractory Myelodysplastic Syndrome. Blood 2019, 134: 565. DOI: 10.1182/blood-2019-124994.Peer-Reviewed Original ResearchStock/stock optionsTreatment-emergent adverse eventsProgression-free survivalMedian progression-free survivalAbbVie IncOverall survivalFebrile neutropeniaStable diseaseMarrow blastsMyelodysplastic syndromeBcl-2 inhibitorsAstra ZenecaFrequent treatment-emergent adverse eventsInternational Working Group 2006 criteriaSerious treatment-emergent adverse eventsAllogeneic stem cell transplantationAdvisory CommitteeDaiichi SankyoCycles of AZACycles of decitabineECOG performance statusPhase 1b studyPhase 2 dosePredominant grade 3Refractory myelodysplastic syndrome
2015
Stabilization of Myelodysplastic Syndromes (MDS) Following Hypomethylating Agent (HMAs) Failure Using the Immune Checkpoint Inhibitor Ipilimumab: A Phase I Trial
Zeidan A, Zeidner J, Duffield A, Knaus H, Ferguson A, Sheldon K, DeZern A, Gojo I, Gore S, Streicher H, Luznik L, Smith B. Stabilization of Myelodysplastic Syndromes (MDS) Following Hypomethylating Agent (HMAs) Failure Using the Immune Checkpoint Inhibitor Ipilimumab: A Phase I Trial. Blood 2015, 126: 1666. DOI: 10.1182/blood.v126.23.1666.1666.Peer-Reviewed Original ResearchOverall survivalStable diseaseEnd of inductionMyelodysplastic syndromeFirst doseIpilimumab useMaintenance doseAnti-cytotoxic T-lymphocyte-associated protein 4 antibodyDose levelsInternational Working Group 2006 criteriaMedian white blood cell countImmune checkpoint inhibition therapyImmune checkpoint inhibitor ipilimumabMedian absolute neutrophil countAllogeneic stem cell transplantationWhite blood cell countT cell receptor repertoireBM blast percentageCheckpoint inhibitor ipilimumabDose-escalation partGrade 3 irAEsOngoing stable diseasePhase 1b studyProlonged disease stabilizationTolerability of ipilimumabResults of a Phase 2 Trial of High Dose Lenalidomide Monotherapy in Patients with Relapsed/Refractory Higher-Risk Myelodysplastic Syndromes or Acute Myeloid Leukemia with Trilineage Dysplasia
Zeidan A, Smith B, Carraway H, Gojo I, Sakoian S, Gore S, DeZern A. Results of a Phase 2 Trial of High Dose Lenalidomide Monotherapy in Patients with Relapsed/Refractory Higher-Risk Myelodysplastic Syndromes or Acute Myeloid Leukemia with Trilineage Dysplasia. Blood 2015, 126: 2901. DOI: 10.1182/blood.v126.23.2901.2901.Peer-Reviewed Original ResearchHigh-risk myelodysplastic syndromeOverall hematologic response rateHigh-dose lenalidomideCycles of lenalidomideNon-hematologic toxicitiesAcute myeloid leukemiaOverall survivalTrilineage dysplasiaEntire cohortMyelodysplastic syndromePlatelet countGrade 3Myeloid leukemiaInternational Working Group 2006 criteriaJohns Hopkins Institutional Review BoardMedian white blood cell countSingle-arm phase II studyBone marrow blast percentageUnderwent bone marrow transplantationWhite blood cell countPhase 2 clinical trialHematologic response rateHigher risk MDSPoor-risk karyotypeCycles of therapyLenalidomide Treatment for Lower Risk Nondeletion 5q Myelodysplastic Syndromes Patients Yields Higher Response Rates When Used Before Azacitidine
Zeidan AM, Al Ali N, Padron E, Lancet J, List A, Komrokji RS. Lenalidomide Treatment for Lower Risk Nondeletion 5q Myelodysplastic Syndromes Patients Yields Higher Response Rates When Used Before Azacitidine. Clinical Lymphoma Myeloma & Leukemia 2015, 15: 705-710. PMID: 26440749, DOI: 10.1016/j.clml.2015.08.083.Peer-Reviewed Original ResearchConceptsLower-risk myelodysplastic syndromesFirst-line therapyErythropoiesis-stimulating agentsFailure of treatmentTreatment failureInternational Working Group 2006 criteriaResponse rateSecond-line therapyMyelodysplastic syndrome patientsHigh response rateChromosome 5q deletionAzacitidine useHematologic improvementLenalidomide treatmentOverall survivalAnemic patientsMyelodysplastic syndromeSyndrome patientsLarge cohortLenalidomideAzacitidinePatientsLeukemic progressionClinical databaseTherapy
2014
The Prognostic Utility of the Current Risk Models in Predicting Outcomes of Patients (pts) with Higher-Risk Myelodysplastic Syndromes (HR-MDS) Treated with Hypomethylating Agents (HMA)
Zeidan A, Sekeres M, Garcia-Manero G, Barnard J, Al Ali N, Zimmerman C, Roboz G, Steensma D, DeZern A, Jabbour E, Kantarjian H, Zell K, Wang Q, Gore S, Nazha A, Maciejewski J, List A, Komrokji R. The Prognostic Utility of the Current Risk Models in Predicting Outcomes of Patients (pts) with Higher-Risk Myelodysplastic Syndromes (HR-MDS) Treated with Hypomethylating Agents (HMA). Blood 2014, 124: 1935. DOI: 10.1182/blood.v124.21.1935.1935.Peer-Reviewed Original ResearchMD Anderson Prognostic Scoring SystemHigh-risk myelodysplastic syndromeInternational Prognostic Scoring SystemMedian overall survivalHematopoietic cell transplantationPrognostic scoring systemOverall response rateOverall survivalHMA therapyHypomethylating agentComplete responseScoring systemStable diseaseHematologic improvementPartial responseProgressive diseaseConfidence intervalsInternational Working Group 2006 criteriaMDS Clinical Research ConsortiumPrognostic modelRevised International Prognostic Scoring SystemRisk categoriesBoehringer Ingelheim CorpCycles of therapyMarrow complete response