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 SocietyA Phase I Study of CC-90002, a Monoclonal Antibody Targeting CD47, in Patients with Relapsed and/or Refractory (R/R) Acute Myeloid Leukemia (AML) and High-Risk Myelodysplastic Syndromes (MDS): Final Results
Zeidan A, DeAngelo D, Palmer J, Seet C, Tallman M, Wei X, Li Y, Hock N, Burgess M, Hege K, Stock W. A Phase I Study of CC-90002, a Monoclonal Antibody Targeting CD47, in Patients with Relapsed and/or Refractory (R/R) Acute Myeloid Leukemia (AML) and High-Risk Myelodysplastic Syndromes (MDS): Final Results. Blood 2019, 134: 1320. DOI: 10.1182/blood-2019-125363.Peer-Reviewed Original ResearchTreatment-emergent adverse eventsR AMLHigh-risk myelodysplastic syndromeAnti-drug antibodiesAcute myeloid leukemiaMyelodysplastic syndromeADC therapeuticsJazz PharmaceuticalsDaiichi SankyoCelgene CorporationFebrile neutropeniaDose levelsDevelopment of ADAGrade treatment-emergent adverse eventsSerious treatment-emergent adverse eventsGeneral physical health deteriorationPhase I multicenter studyPrior stem cell transplantRefractory acute myeloid leukemiaRed blood cell transfusionBCR-ABL kinase domainAdvisory CommitteeAnti-CD47 monoclonal antibodyExcess blasts-2Grade 4 sepsisA 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 SystemEfficacy and Safety of Azacitidine (AZA) in Combination with the Anti-PD-L1 Durvalumab (durva) for the Front-Line Treatment of Older Patients (pts) with Acute Myeloid Leukemia (AML) Who Are Unfit for Intensive Chemotherapy (IC) and Pts with Higher-Risk Myelodysplastic Syndromes (HR-MDS): Results from a Large, International, Randomized Phase 2 Study
Zeidan A, Cavenagh J, Voso M, Taussig D, Tormo M, Boss I, Copeland W, Gray V, Previtali A, O'Connor T, Rose S, Beach C, Silverman L. Efficacy and Safety of Azacitidine (AZA) in Combination with the Anti-PD-L1 Durvalumab (durva) for the Front-Line Treatment of Older Patients (pts) with Acute Myeloid Leukemia (AML) Who Are Unfit for Intensive Chemotherapy (IC) and Pts with Higher-Risk Myelodysplastic Syndromes (HR-MDS): Results from a Large, International, Randomized Phase 2 Study. Blood 2019, 134: 829. DOI: 10.1182/blood-2019-122896.Peer-Reviewed Original ResearchHigh-risk myelodysplastic syndromePD-L1 surface expressionAcute myeloid leukemiaPlatinum-containing chemotherapyPhase 2 studyIntensive chemotherapyArm AMyeloid blastsCelgene CorporationAML ptsMedian OSPD-L1AML cohortDisease progressionSurface expressionTreatment groupsTreatment cyclesECOG performance status 0First large randomized trialLarger phase 2 studiesPD-L1 blocking antibodiesRandomized phase 2 studyConcurrent platinum-based chemotherapyResponse criteriaSafety of azacitidinePharmacokinetic 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 dependenceAssessment 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 transfusionClinical 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 StudyEnasidenib Plus Azacitidine Significantly Improves Complete Remission and Overall Response Compared with Azacitidine Alone in Patients with Newly Diagnosed Acute Myeloid Leukemia (AML) with Isocitrate Dehydrogenase 2 (IDH2) Mutations: Interim Phase II Results from an Ongoing, Randomized Study
DiNardo C, Schuh A, Stein E, Fernandez P, Wei A, De Botton S, Zeidan A, Fathi A, Quek L, Kantarjian H, Frattini M, Lersch F, Gong J, Franovic A, MacBeth K, Vyas P, Döhner H. Enasidenib Plus Azacitidine Significantly Improves Complete Remission and Overall Response Compared with Azacitidine Alone in Patients with Newly Diagnosed Acute Myeloid Leukemia (AML) with Isocitrate Dehydrogenase 2 (IDH2) Mutations: Interim Phase II Results from an Ongoing, Randomized Study. Blood 2019, 134: 643. DOI: 10.1182/blood-2019-130362.Peer-Reviewed Original ResearchOverall response rateAcute myeloid leukemiaDuration of responseMorphologic leukemia-free stateBone marrow mononuclear cellsAZA armComplete remissionIntensive chemotherapyCelgene CorporationResponse rateDaiichi SankyoVariant allele frequencySpeakers bureauPTC TherapeuticsPartial remissionData cutoffGrade 3Phase I/II studyMedian DORAdvisory CommitteeSeattle GeneticsForty-sevenConventional care regimensIDH differentiation syndromePoor-risk cytogeneticsThe Impact of the 2011 European Leukemianet (ELN) Guidelines for Philadelphia Chromosome-Negative Classical Myeloproliferative Neoplasms on Therapeutic Phlebotomy and Hydroxyurea Use in Patients with Polycythemia Vera and Essential Thrombocythemia
Podoltsev N, Wang R, Shallis R, Huntington S, Zeidan A, Gore S, Davidoff A, Ma X. The Impact of the 2011 European Leukemianet (ELN) Guidelines for Philadelphia Chromosome-Negative Classical Myeloproliferative Neoplasms on Therapeutic Phlebotomy and Hydroxyurea Use in Patients with Polycythemia Vera and Essential Thrombocythemia. Blood 2019, 134: 2125. DOI: 10.1182/blood-2019-127563.Peer-Reviewed Original ResearchTherapeutic phlebotomyPopulation-based cohortPV patientsELN guidelinesET patientsPolycythemia veraEssential thrombocythemiaGuideline publicationCelgene CorporationCytoreductive therapyHU useMonthly proportionBoehringer IngelheimLarge population-based cohortAdvisory CommitteeDaiichi SankyoOlder adultsEuropean LeukemiaNet guidelinesEnd Results-MedicareProportion of patientsHealthcare Common Procedure Coding System codesPopulation-based studyPatterns of careTreatment of patientsPart D claimsClinical Effectiveness of Hypomethylating Agents (HMAs) and Lenalidomide (Len) in Older Patients (pts) with Refractory Anemia with Ring Sideroblasts: A Large Population-Based Study in the United States (US)
Wang X, Wang R, Zhang C, Zeidan A, Podoltsev N, Huntington S, Gore S, Davidoff A, Ma X. Clinical Effectiveness of Hypomethylating Agents (HMAs) and Lenalidomide (Len) in Older Patients (pts) with Refractory Anemia with Ring Sideroblasts: A Large Population-Based Study in the United States (US). Blood 2019, 134: 4748. DOI: 10.1182/blood-2019-128821.Peer-Reviewed Original ResearchPopulation-based studyLR-MDSMedian overall survivalOverall survivalClinical effectivenessHypomethylating agentCelgene CorporationMedian durationRed blood cellsMedian timeRing sideroblastsBoehringer IngelheimAdvisory CommitteeLarge population-based studyDaiichi SankyoOlder adultsAbnormal erythroid precursorsTransfusion independence rateEnd Results-MedicareHigh-risk MDSErythropoiesis-stimulating agentsKaplan-Meier statisticsComparative clinical effectivenessEnd of studyPart D coveragePatterns of Care and Clinical Outcomes with 7+3 Induction Chemotherapy for Patients (pts) with Acute Myeloid Leukemia (AML) in the United States (US): A Large Population-Based Study
Zeidan A, Podoltsev N, Wang X, Bewersdorf J, Shallis R, Huntington S, Neparidze N, Giri S, Gore S, Ma X, Davidoff A, Wang R. Patterns of Care and Clinical Outcomes with 7+3 Induction Chemotherapy for Patients (pts) with Acute Myeloid Leukemia (AML) in the United States (US): A Large Population-Based Study. Blood 2019, 134: 116. DOI: 10.1182/blood-2019-126643.Peer-Reviewed Original ResearchBone marrow aspirate/biopsyHigh-volume hospitalsAcute myeloid leukemiaMedium-volume hospitalsAML ptsInduction chemotherapyIntensive care unitAnti-infective medicationsAnti-viral medicationInpatient stayCelgene CorporationAntifungal prophylaxisHospital deathVolume hospitalsHospital volumeMechanical ventilationLarge population-based retrospective cohort studyPopulation-based retrospective cohort studyCytarabine-based induction chemotherapyBoehringer IngelheimAdvisory CommitteeLarge population-based studyDaiichi SankyoInduction-related mortalityMedium-volume institutionsIncidence and Risk Factors of Second Malignancies Among Medicare Beneficiaries with Newly-Diagnosed Philadelphia Chromosome-Negative Classical Myeloproliferative Neoplasms Receiving Cytoreductive Therapy with Hydroxyurea
Wang R, Shallis R, Huntington S, Zeidan A, Gore S, Davidoff A, Ma X, Podoltsev N. Incidence and Risk Factors of Second Malignancies Among Medicare Beneficiaries with Newly-Diagnosed Philadelphia Chromosome-Negative Classical Myeloproliferative Neoplasms Receiving Cytoreductive Therapy with Hydroxyurea. Blood 2019, 134: 330. DOI: 10.1182/blood-2019-127568.Peer-Reviewed Original ResearchMyeloid hematological malignanciesHU usersPopulation-based studyHematological malignanciesCumulative incidenceCelgene CorporationMPN diagnosisCytoreductive therapySolid malignanciesGray's testPolycythemia veraMPN patientsEssential thrombocythemiaContinuous Part D coverageBoehringer IngelheimAdvisory CommitteeLarge population-based studyDaiichi SankyoImpact of hydroxyureaRetrospective cohort studyElixhauser comorbidity scorePV/ET myelofibrosisRisk regression modelsSAS version 9.4Part D coverageThe 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 Outcomes of Older Patients (pts) with Acute Myeloid Leukemia (AML) Receiving Hypomethylating Agents (HMAs): A Large Population-Based Study in the United States
Zeidan A, Wang R, Wang X, Shallis R, Podoltsev N, Bewersdorf J, Huntington S, Neparidze N, Giri S, Gore S, Davidoff A, Ma X. Clinical Outcomes of Older Patients (pts) with Acute Myeloid Leukemia (AML) Receiving Hypomethylating Agents (HMAs): A Large Population-Based Study in the United States. Blood 2019, 134: 646. DOI: 10.1182/blood-2019-127398.Peer-Reviewed Original ResearchRBC transfusion dependenceAcute myeloid leukemiaMedian overall survivalTransfusion independenceOverall survivalTransfusion dependenceHypomethylating agentCelgene CorporationHMA initiationIntensive chemotherapyOS probabilityMedian timeMultivariable analysisMultivariable Cox proportional hazards modelsBoehringer IngelheimAdvisory CommitteeCox proportional hazards modelDaiichi SankyoChemotherapy-related hospitalizationMo of diagnosisRBC transfusion independenceImproved overall survivalClinical trial evidenceInferior overall survivalWorse overall survival
2018
Impact of Leukapheresis and Time to Chemotherapy on Outcomes of Newly Diagnosed Patients (pts) with Acute Myeloid Leukemia (AML) Presenting with Hyperleukocytosis: An Analysis from a Large International Patient Cohort
Stahl M, Wei W, Montesinos P, Lengline E, Shallis R, Neukirchen J, Bhatt V, Sekeres M, Fathi A, Konig H, Luger S, Khan I, Roboz G, Cluzeau T, Martínez-Cuadron D, Raffoux E, Germing U, Umakanthan J, Mukherjee S, Brunner A, Miller A, McMahon C, Ritchie E, Rodríguez-Veiga R, Itzykson R, Boluda B, Rabian F, Tormo M, Cruz E, Rabinovich E, Yoo B, Podoltsev N, Gore S, Zeidan A. Impact of Leukapheresis and Time to Chemotherapy on Outcomes of Newly Diagnosed Patients (pts) with Acute Myeloid Leukemia (AML) Presenting with Hyperleukocytosis: An Analysis from a Large International Patient Cohort. Blood 2018, 132: 1428. DOI: 10.1182/blood-2018-99-112495.Peer-Reviewed Original ResearchWhite blood cell countInitiation of ICSAcute myeloid leukemiaUse of leukapheresisImpact of leukapheresisTumor lysis syndromeHours of presentationOdds of deathCytogenetic risk groupOverall survivalTime of presentationUnivariate analysisMultivariate analysisAstex PharmaceuticalsSpeakers bureauHazard ratioDaiichi SankyoRisk groupsEastern Cooperative Oncology Group performance statusJanssen PharmaceuticalsJazz PharmaceuticalsCleveland Clinic Taussig Cancer InstituteAdverse cytogenetic risk groupPoor cytogenetic risk groupCelgene CorporationOutcomes of Patients with Newly-Diagnosed Acute Myeloid Leukemia and Hyperleukocytosis Who Did Not Undergo Intensive Chemotherapy: Results from a Large International Database
Shallis R, Stahl M, Wei W, Montesinos P, Lengline E, Neukirchen J, Bhatt V, Sekeres M, Fathi A, Konig H, Luger S, Khan I, Roboz G, Cluzeau T, Martínez-Cuadron D, Raffoux E, Germing U, Umakanthan J, Mukherjee S, Brunner A, Miller A, McMahon C, Ritchie E, Rodríguez-Veiga R, Itzykson R, Boluda B, Rabian F, Tormo M, Cruz E, Podoltsev N, Gore S, Zeidan A. Outcomes of Patients with Newly-Diagnosed Acute Myeloid Leukemia and Hyperleukocytosis Who Did Not Undergo Intensive Chemotherapy: Results from a Large International Database. Blood 2018, 132: 3999. DOI: 10.1182/blood-2018-99-119755.Peer-Reviewed Original ResearchTumor lysis syndromeIntensive chemotherapyIntensive care unitOverall survivalClinical evidenceAstex PharmaceuticalsSpeakers bureauDaiichi SankyoMedian OSWorse OSAML patientsPlatelet countEastern Cooperative Oncology Group performance statusJazz PharmaceuticalsCleveland Clinic Taussig Cancer InstituteJanssen PharmaceuticalsOne-year OS probabilityCelgene CorporationAdvisory CommitteeMDS International FoundationPoor-risk AMLBest supportive careLow-dose cytarabineMedian overall survivalOutcomes of patientsCharacteristics, Treatment Patterns and Outcomes Among Newly Diagnosed Patients (pts) with Acute Myeloid Leukemia (AML) Who Present with Hyperleukocytosis: Findings from a Large International Patient Cohort
Stahl M, Wei W, Montesinos P, Lengline E, Shallis R, Neukirchen J, Bhatt V, Sekeres M, Fathi A, Konig H, Luger S, Khan I, Roboz G, Cluzeau T, Martínez-Cuadron D, Raffoux E, Germing U, Umakanthan J, Mukherjee S, Brunner A, Miller A, McMahon C, Ritchie E, Rodríguez-Veiga R, Itzykson R, Boluda B, Rabian F, Tormo M, Cruz E, Rabinovich E, Yoo B, Podoltsev N, Gore S, Zeidan A. Characteristics, Treatment Patterns and Outcomes Among Newly Diagnosed Patients (pts) with Acute Myeloid Leukemia (AML) Who Present with Hyperleukocytosis: Findings from a Large International Patient Cohort. Blood 2018, 132: 4040. DOI: 10.1182/blood-2018-99-112974.Peer-Reviewed Original ResearchWhite blood cell countMedian overall survivalAcute myeloid leukemiaHematopoietic stem cell transplantIntensive chemotherapyTumor lysis syndromeOverall survivalTime of presentationComplete remissionAstex PharmaceuticalsSpeakers bureauPartial remissionTreatment patternsDaiichi SankyoJazz PharmaceuticalsCleveland Clinic Taussig Cancer InstituteJanssen PharmaceuticalsMedian white blood cell countHigher white blood cell countCelgene CorporationLong-term clinical outcomesAdvisory CommitteeImpact of leukapheresisIncomplete count recoveryMDS International Foundation