2023
Patient-Reported Outcomes (PRO) of Luspatercept Versus Epoetin Alfa in Erythropoiesis-Stimulating Agent (ESA)-Naïve, Transfusion-Dependent (TD), Lower-Risk Myelodysplastic Syndromes (LR-MDS): Results from the Phase 3 COMMANDS Study
Oliva E, Platzbecker U, Della Porta M, Garcia-Manero G, Santini V, Fenaux P, Shortt J, Komrokji R, Pelligra C, Guo S, Lord-Bessen J, Xiao H, Yucel A, Miteva D, Rose S, Kreitz S, Sekeres M, Zeidan A. Patient-Reported Outcomes (PRO) of Luspatercept Versus Epoetin Alfa in Erythropoiesis-Stimulating Agent (ESA)-Naïve, Transfusion-Dependent (TD), Lower-Risk Myelodysplastic Syndromes (LR-MDS): Results from the Phase 3 COMMANDS Study. Blood 2023, 142: 4596. DOI: 10.1182/blood-2023-174660.Peer-Reviewed Original ResearchLower-risk myelodysplastic syndromesEORTC QLQ-C30Patient-reported outcomesErythropoietin-stimulating agentsEpoetin alfaQLQ-C30FACT-AnSustained improvementTreatment armsESA-naïveTransfusion-DependentTreatment tolerabilityStratified Cox proportional hazards regression modelDay 1Cox proportional hazards regression modelCancer Therapy-Anemia (FACT-An) questionnaireLife Questionnaire Core 30Proportional hazards regression modelsMajority of patientsTreatment side effectsPost-baseline visitTransfusion-dependent patientsErythropoiesis stimulating agentsHazards regression modelsPhase 3
2022
AML-484 First Results of a Phase II Study (STIMULUS-AML1) Investigating Sabatolimab + Azacitidine + Venetoclax in Patients With Newly Diagnosed Acute Myeloid Leukemia (ND AML)
Zeidan A, Westermann J, Kovacsovics T, Assouline S, Schuh A, Kim H, Macias G, Sanford D, Luskin M, Stein E, Malek K, Lyu J, Stegert M, Esteve J. AML-484 First Results of a Phase II Study (STIMULUS-AML1) Investigating Sabatolimab + Azacitidine + Venetoclax in Patients With Newly Diagnosed Acute Myeloid Leukemia (ND AML). Clinical Lymphoma Myeloma & Leukemia 2022, 22: s255. DOI: 10.1016/s2152-2650(22)01303-9.Peer-Reviewed Original ResearchTreatment-related AEsDose-escalation partDose-limiting toxicityIntensive chemotherapyDosage reductionCohort 2Acute myeloid leukemiaDose interruptionFebrile neutropeniaSerious AEsExpansion cohortStudy patientsTreatment discontinuationAdult patientsDurable responsesNeutrophil countTim-3Agent therapyMyelodysplastic syndromePlatelet countSafety profilePatient outcomesMyeloid leukemiaPatientsDay 1A randomized phase 2 trial of azacitidine with or without durvalumab as first-line therapy for older patients with AML
Zeidan AM, Boss I, Beach C, Copeland WB, Thompson E, Fox BA, Hasle VE, Hellmann A, Taussig D, Tormo M, Voso MT, Cavenagh J, O'Connor T, Previtali A, Rose S, Silverman LR. A randomized phase 2 trial of azacitidine with or without durvalumab as first-line therapy for older patients with AML. Blood Advances 2022, 6: 2219-2229. PMID: 34933333, PMCID: PMC9006260, DOI: 10.1182/bloodadvances.2021006138.Peer-Reviewed Original ResearchConceptsAcute myeloid leukemiaFirst-line therapyOlder patientsDay 1First-line combination therapyTreatment-emergent adverse eventsRandomized phase 2 trialSafety of durvalumabNew safety signalsPD-L1 expressionPhase 2 studyPhase 2 trialDuration of responseOverall response rateDurvalumab 1500Adverse eventsOverall survivalClinical efficacyCombination therapyMyeloid leukemiaSafety signalsTreatment responseCombination treatmentAzacitidineResponse rate
2021
Phase 3 VERONA study of venetoclax with azacitidine to assess change in complete remission and overall survival in treatment-naïve higher-risk myelodysplastic syndromes.
Zeidan A, Garcia J, Fenaux P, Platzbecker U, Miyazaki Y, Xiao Z, Zhou Y, Naqvi K, Kye S, Garcia-Manero G. Phase 3 VERONA study of venetoclax with azacitidine to assess change in complete remission and overall survival in treatment-naïve higher-risk myelodysplastic syndromes. Journal Of Clinical Oncology 2021, 39: tps7054-tps7054. DOI: 10.1200/jco.2021.39.15_suppl.tps7054.Peer-Reviewed Original ResearchHematopoietic stem cell transplantOverall survivalAcute myeloid leukemiaCR rateComplete remissionTransfusion independenceCell transplantationDisease progressionMyeloid leukemiaDay 1B-cell lymphoma-2 inhibitorRed blood cell transfusion independenceHigh-risk myelodysplastic syndromeAllogenic stem cell transplantationCo-morbid patientsIWG 2006 criteriaPhase 1b studyPlatelet transfusion independenceMedian overall survivalFirst-line treatmentPhase 3 studyBone marrow blastsDe novo patientsHematopoietic cell transplantationStudy days 1
2020
Blast MRD AML-1 Trial: Blockade of PD-1 Added to Standard Therapy to Target Measurable Residual Disease in Acute Myeloid Leukemia (AML) 1- an Investigator-Initiated, CTEP-Sponsored, Randomized Phase 2 Study of the Anti-PD-1 Antibody Pembrolizumab in Combination with Conventional Intensive Chemotherapy (IC) As Frontline Therapy in Patients with Acute Myeloid Leukemia (AML)
Zeidan A, Boddu P, Wood B, Zelterman D, Little R, Ivy S, Caldwell A, Sanchez-Espiridion B, Alatrash G, Sharon E, Radich J. Blast MRD AML-1 Trial: Blockade of PD-1 Added to Standard Therapy to Target Measurable Residual Disease in Acute Myeloid Leukemia (AML) 1- an Investigator-Initiated, CTEP-Sponsored, Randomized Phase 2 Study of the Anti-PD-1 Antibody Pembrolizumab in Combination with Conventional Intensive Chemotherapy (IC) As Frontline Therapy in Patients with Acute Myeloid Leukemia (AML). Blood 2020, 136: 15. DOI: 10.1182/blood-2020-139668.Peer-Reviewed Original ResearchMRD-negative complete responsesAcute myeloid leukemiaMinimal residual diseaseEvent-free survivalImmune checkpoint inhibitionPhase 2 studyIntensive chemotherapyDuration of responseComplete responseOverall survivalPD-1AML patientsDay 1Free survivalHematologic improvementInitial treatmentStudy armsResidual diseaseDay IVLeukemia-specific T-cell responsesSingle-arm phase 2 studyPD-1/PD-L1 pathwayTherapy-related acute myeloid leukemiaCancer Therapy Evaluation ProgramImmune cell subsets analysisBlast MRD AML-2: Blockade of PD-1 Added to Standard Therapy to Target Measurable Residual Disease (MDR) in Acute Myeloid Leukemia (AML) 2- a Randomized Phase 2 Study of the Venetoclax, Azacitidine, and Pembrolizumab Versus Venetoclax and Azacitidine As First Line Therapy in Older Patients with AML Who Are Ineligible or Who Refuse Intensive Chemotherapy
Zeidan A, Boddu P, Wood B, Zelterman D, Little R, Ivy S, Caldwell A, Sanchez-Espiridion B, Alatrash G, Sharon E, Radich J. Blast MRD AML-2: Blockade of PD-1 Added to Standard Therapy to Target Measurable Residual Disease (MDR) in Acute Myeloid Leukemia (AML) 2- a Randomized Phase 2 Study of the Venetoclax, Azacitidine, and Pembrolizumab Versus Venetoclax and Azacitidine As First Line Therapy in Older Patients with AML Who Are Ineligible or Who Refuse Intensive Chemotherapy. Blood 2020, 136: 11-12. DOI: 10.1182/blood-2020-139752.Peer-Reviewed Original ResearchEvent-free survivalDuration of responseMRD-negative CRIntensive chemotherapyOverall survivalDay 1Complete remissionFree survivalHematologic improvementOlder patientsSecondary AMLPD-1Study armsAML patientsInitial treatmentHematologic disordersLeukemia-specific T-cell responsesCancer Therapy Evaluation ProgramCR/complete remissionImmune cell subsets analysisRandomized phase 2 studyRandomized phase 2 trialRandomized phase II studyAllogeneic stem cell transplantBetter long-term clinical outcomes
2019
Pharmacodynamic Responses to CC-90009, a Novel Cereblon E3 Ligase Modulator, in a Phase I Dose-Escalation Study in Relapsed or Refractory Acute Myeloid Leukemia (R/R AML)
Fan J, Wang H, Couto S, Yao T, Uy G, Zeidan A, Minden M, Montesinos P, DeAngelo D, Altman J, Koprivnikar J, Vyas P, Fløisand Y, Vidriales M, Gjertsen B, Buchholz T, Pourdehnad M, Pierce D. Pharmacodynamic Responses to CC-90009, a Novel Cereblon E3 Ligase Modulator, in a Phase I Dose-Escalation Study in Relapsed or Refractory Acute Myeloid Leukemia (R/R AML). Blood 2019, 134: 2547. DOI: 10.1182/blood-2019-124291.Peer-Reviewed Original ResearchNovel cereblon E3 ligase modulatorCereblon E3 ligase modulatorPeripheral blood mononuclear cellsCC-90009T cellsPharmacodynamic responseCelgene CorporationDaiichi SankyoSpeakers bureauR AMLAML blastsIntegrated stress responseBlast cellsDay 1Dose levelsPhase I dose-escalation studyRefractory acute myeloid leukemiaI dose-escalation studyAdvisory CommitteeBone marrow core biopsiesAntileukemic activitySeattle GeneticsPhase IHigh-dose cohortNorwegian Cancer SocietySafety, Efficacy and Biomarker Analysis of a Phase 1b/2 Study of Onvansertib (ONV), a Polo-like Kinase 1 (PLK1) Inhibitor, in Combination with Low-Dose Cytarabine (LDAC) or Decitabine (DEC) in Patients (pts) with Relapsed/Refractory Acute Myeloid Leukemia (R/R AML)
Zeidan A, Schiller G, Lin T, Becker P, Patel P, Wang E, Spira A, Tsai M, Ridinger M, Croucher P, Erlander M, Silberman S. Safety, Efficacy and Biomarker Analysis of a Phase 1b/2 Study of Onvansertib (ONV), a Polo-like Kinase 1 (PLK1) Inhibitor, in Combination with Low-Dose Cytarabine (LDAC) or Decitabine (DEC) in Patients (pts) with Relapsed/Refractory Acute Myeloid Leukemia (R/R AML). Blood 2019, 134: 230. DOI: 10.1182/blood-2019-126262.Peer-Reviewed Original ResearchPositive ptsBiomarker positivityPhase 1bBristol-Myers SquibbSpeakers bureauObjective responseCount recoveryPreliminary efficacyBlood samplesNegative groupRelapsed/Refractory Acute Myeloid LeukemiaADC therapeuticsDay 1Jazz PharmaceuticalsRefractory acute myeloid leukemiaBoehringer IngelheimDaiichi SankyoIncomplete count recoveryPhase 1b/2 studyPreclinical AML modelsSubset of ptsLow-dose cytarabinePredictive gene expression signaturesDose-escalation trialPlatelet count recoveryThe VITAL Trial: Phase II Trial of Vosaroxin and Infusional Cytarabine for Frontline Treatment of acute Myeloid Leukemia
Strickland S, Podoltsev N, Mohan S, Zeidan A, Childress M, Ayers G, Byrne M, Gore S, Stuart R, Savona M. The VITAL Trial: Phase II Trial of Vosaroxin and Infusional Cytarabine for Frontline Treatment of acute Myeloid Leukemia. Blood 2019, 134: 180. DOI: 10.1182/blood-2019-131520.Peer-Reviewed Original ResearchIntermediate-dose cytarabineCR/CRiAdverse eventsOverall survivalInfusional cytarabineOral mucositisCardiac toxicityResponse assessmentCelgene CorporationAML ptsOral cryotherapyBoehringer IngelheimMedian ageCR rateDay 1Large randomized phase 3 trialsTwo-stage phase II studyClass anticancer quinolone derivativeCR/CRi rateRandomized phase 3 trialHematopoietic stem cell transplantAdvisory CommitteeDaiichi SankyoAcute cardiac toxicityIncomplete count recoveryClinical Activity of CC-90009, a Cereblon E3 Ligase Modulator and First-in-Class GSPT1 Degrader, As a Single Agent in Patients with Relapsed or Refractory Acute Myeloid Leukemia (R/R AML): First Results from a Phase I Dose-Finding Study
Uy G, Minden M, Montesinos P, DeAngelo D, Altman J, Koprivnikar J, Vyas P, Fløisand Y, Vidriales M, Gjertsen B, Esteve J, Buchholz T, Couto S, Fan J, Hanna B, Li L, Pierce D, Hege K, Pourdehnad M, Zeidan A. Clinical Activity of CC-90009, a Cereblon E3 Ligase Modulator and First-in-Class GSPT1 Degrader, As a Single Agent in Patients with Relapsed or Refractory Acute Myeloid Leukemia (R/R AML): First Results from a Phase I Dose-Finding Study. Blood 2019, 134: 232. DOI: 10.1182/blood-2019-123966.Peer-Reviewed Original ResearchTreatment-emergent adverse eventsCereblon E3 ligase modulatorSystemic inflammatory response syndromeCC-90009Phase 1 studyR AMLHighest dose levelDose levelsCelgene CorporationDaiichi SankyoSpeakers bureauGrade 3/4 treatment-emergent adverse eventsDay 1Jazz PharmaceuticalsObserved treatment-emergent adverse eventOpen-label phase 1 studySerious treatment-emergent adverse eventsHyperglycemic hyperosmolar nonketotic syndromeIncomplete blood count recoveryMorphologic leukemia-free stateRefractory acute myeloid leukemiaHigh-risk myelodysplastic syndromeAdvisory CommitteeAntileukemic activityI Dose-Finding Study
2018
Effective Immunomodulation with Pomalidomide Beginning at Early Lymphocyte Recovery during Induction Timed Sequential Therapy (TST) for Acute Myeloid Leukemia (AML) and High-Risk Myelodysplasia (HR-MDS)
Zeidner J, Knaus H, Zeidan A, Blackford A, Montiel-Esparza R, Prince G, Gondek L, Ghiaur G, Showel M, DeZern A, Pratz K, Smith B, Levis M, Foster M, Coombs C, Streicher H, Karp J, Luznik L, Gojo I. Effective Immunomodulation with Pomalidomide Beginning at Early Lymphocyte Recovery during Induction Timed Sequential Therapy (TST) for Acute Myeloid Leukemia (AML) and High-Risk Myelodysplasia (HR-MDS). Blood 2018, 132: 335. DOI: 10.1182/blood-2018-99-114961.Peer-Reviewed Original ResearchEarly lymphocyte recoveryTimed sequential therapyAcute myeloid leukemiaMinimal residual diseaseT cellsLymphocyte recoveryCR rateMedian timeDay 1Phase 1 dose-escalation studyALT/AST elevationsAcute respiratory distress syndromeSecondary acute myeloid leukemiaAdverse-risk cytogeneticsHR-MDS patientsNon-hematologic gradePoor-risk subsetStandard induction therapyAcute kidney injuryMedian overall survivalPeripheral blood CD4Disease-free survivalDose-escalation studyEvent-free survivalGrade 3 rash
2016
Phase 1 Study of Pomalidomide Given at the Time of Early Lymphocyte Recovery after Induction Timed Sequential Chemotherapy in Newly Diagnosed Acute Myeloid Leukemia (AML) and High-Risk Myelodysplastic Syndrome (HR-MDS)
Zeidner J, Montiel-Esparza R, Knaus H, Berglund S, Zeidan A, McCurdy S, Prince G, Gondek L, Ghiaur G, Showel M, DeZern A, Pratz K, Smith B, Levis M, Foster M, Jamieson K, Van Deventer H, Streicher H, Karp J, Luznik L, Gojo I. Phase 1 Study of Pomalidomide Given at the Time of Early Lymphocyte Recovery after Induction Timed Sequential Chemotherapy in Newly Diagnosed Acute Myeloid Leukemia (AML) and High-Risk Myelodysplastic Syndrome (HR-MDS). Blood 2016, 128: 2820. DOI: 10.1182/blood.v128.22.2820.2820.Peer-Reviewed Original ResearchEarly lymphocyte recoveryAcute myeloid leukemiaWhite blood cell countComplete remissionAdverse eventsT cellsLymphocyte recoveryDay 1Adverse-risk acute myeloid leukaemiaDose levelsALT increasePhase 1 dose-escalation studyAST/ALT increaseContinuous infusion days 1High-risk myelodysplastic syndromeCore-binding factor acute myeloid leukemiaTotal white blood cell countFlow cytometryFactor acute myeloid leukemiaFull recoveryGrade 3 hypoxiaIncomplete platelet recoveryInfusion days 1Common adverse eventsConventional chemotherapy regimens
2011
Escalation Trial of Clofarabine Followed by Escalating Dose of Fractionated Cyclophosphamide in Adults with Relapsed or Refractory Acute Leukemias,
Zeidan A, Carraway H, Yun H, Greer J, Karp J. Escalation Trial of Clofarabine Followed by Escalating Dose of Fractionated Cyclophosphamide in Adults with Relapsed or Refractory Acute Leukemias,. Blood 2011, 118: 3615. DOI: 10.1182/blood.v118.21.3615.3615.Peer-Reviewed Original ResearchRefractory acute leukemiaAbsolute lymphocyte countAbsolute neutrophilic countDose level 1Dose-limiting toxicityOverall response rateAdverse cytogeneticsWhite blood cellsM2/dayClinical responseAcute leukemiaDay 1One-year disease-free survivalPhase I dose-escalation trialMedian absolute lymphocyte countElevated liver function testsAllogeneic stem cell transplantI dose-escalation trialTotal white blood cellsSecond-generation purine nucleoside analogDose level 3Dose level 4Dose of CYGrade 3 pneumoniaHand-foot syndrome