2024
Hypomethylating agents plus venetoclax compared with intensive induction chemotherapy regimens in molecularly defined secondary AML
Shimony S, Bewersdorf J, Shallis R, Liu Y, Schaefer E, Zeidan A, Goldberg A, Stein E, Marcucci G, Lindsley R, Chen E, Ramos Perez J, Stein A, DeAngelo D, Neuberg D, Stone R, Ball B, Stahl M. Hypomethylating agents plus venetoclax compared with intensive induction chemotherapy regimens in molecularly defined secondary AML. Leukemia 2024, 38: 762-768. PMID: 38378841, DOI: 10.1038/s41375-024-02175-0.Peer-Reviewed Original ResearchAssociated with improved OSHypomethylating agentsCPX-351Overall survivalSplicing factor mutationsCo-mutationsAllogeneic hematopoietic stem cell transplantationAssociated with better OSAssociated with worse OSSecondary acute myeloid leukemiaHematopoietic stem cell transplantationMedian overall survivalStem cell transplantationPatients aged >Acute myeloid leukemiaTreated with daunorubicinLiposomal daunorubicinMonosomal karyotypeNRAS/KRAS mutationsImproved OSSecondary AMLMyeloid diseasesMyeloid neoplasmsAML patientsAML treatment
2023
Encouraging Efficacy Observed in Bexmab Study: A Phase 1/2 Study to Assess Safety and Efficacy of Bexmarilimab in Combination with Standard of Care in Myeloid Malignancies
Kontro M, Stein A, Pyörälä M, Rimpiläinen J, Siitonen T, Hollmén M, Fjaellskog M, Pawlitzky I, Zeidan A, Daver N. Encouraging Efficacy Observed in Bexmab Study: A Phase 1/2 Study to Assess Safety and Efficacy of Bexmarilimab in Combination with Standard of Care in Myeloid Malignancies. Blood 2023, 142: 2915. DOI: 10.1182/blood-2023-174912.Peer-Reviewed Original ResearchAcute myeloid leukemiaR AMLCLEVER-1Complete remissionStandard of careBex treatmentAdverse eventsBone marrow cellsHMA failureMarrow CRPatient BMPrior therapyPartial remissionAML patientsMedian numberT cellsDose levelsMyeloid malignanciesHigh-risk MDS patientsMarrow cellsMarrow complete remissionR AML patientsRisk MDS patientsNK cell numbersPhase 1/2 studyData-Driven Harmonization of 2022 Who and ICC Classifications of Myelodysplastic Syndromes/Neoplasms (MDS): A Study By the International Consortium for MDS (icMDS)
Lanino L, Ball S, Bewersdorf J, Marchetti M, Maggioni G, Travaglino E, Al Ali N, Fenaux P, Platzbecker U, Santini V, Diez-Campelo M, Singh A, Jain A, Aguirre L, Tinsley-Vance S, Schwabkey Z, Chan O, Xie Z, Brunner A, Kuykendall A, Bennett J, Buckstein R, Bejar R, Carraway H, DeZern A, Griffiths E, Halene S, Hasserjian R, Lancet J, List A, Loghavi S, Odenike O, Padron E, Patnaik M, Roboz G, Stahl M, Sekeres M, Steensma D, Savona M, Taylor J, Xu M, Sweet K, Sallman D, Nimer S, Hourigan C, Wei A, Sauta E, D'Amico S, Asti G, Castellani G, Borate U, Sanz G, Efficace F, Gore S, Kim T, Daver N, Garcia-Manero G, Rozman M, Orfao A, Wang S, Foucar M, Germing U, Haferlach T, Scheinberg P, Miyazaki Y, Iastrebner M, Kulasekararaj A, Cluzeau T, Kordasti S, van de Loosdrecht A, Ades L, Zeidan A, Komrokji R, Della Porta M. Data-Driven Harmonization of 2022 Who and ICC Classifications of Myelodysplastic Syndromes/Neoplasms (MDS): A Study By the International Consortium for MDS (icMDS). Blood 2023, 142: 998. DOI: 10.1182/blood-2023-186580.Peer-Reviewed Original ResearchBlast countMost patientsTP53 mutationsTET2 mutationsChromosomal abnormalitiesMore TP53 mutationsBone marrow blastsGene mutationsSF3B1 mutationsClinical decision-making processHigh-risk mutationsMarrow blastsMultilineage dysplasiaPatient characteristicsAML patientsClinical entityInternational cohortSHAP analysisMDS casesPatientsClinical relevanceCytogenetic abnormalitiesClinical settingComplex karyotypeU2AF1 mutationsSpliceosome mutations are associated with clinical response in a phase 1b/2 study of the PLK1 inhibitor onvansertib in combination with decitabine in relapsed or refractory acute myeloid leukemia
Croucher P, Ridinger M, Becker P, Lin T, Silberman S, Wang E, Zeidan A. Spliceosome mutations are associated with clinical response in a phase 1b/2 study of the PLK1 inhibitor onvansertib in combination with decitabine in relapsed or refractory acute myeloid leukemia. Annals Of Hematology 2023, 102: 3049-3059. PMID: 37702821, PMCID: PMC10567832, DOI: 10.1007/s00277-023-05442-9.Peer-Reviewed Original ResearchAcute myeloid leukemiaR AML patientsAML patientsMyeloid leukemiaRefractory (R/R) AMLRelapsed/refractory (R/R) AMLHigher CR/CRi ratesCR/CRi rateRefractory acute myeloid leukemiaGene signaturePhase 1b/2 studyPhase 1b/2 trialPhase 1b trialBone marrow blastsSF mutationsBone marrow samplesCRi rateComplete remissionMarrow blastsClinical responseCount recoveryInitial safetyMarrow samplesPotential therapyMolecular predictorsWhat’s Next after Hypomethylating Agents Failure in Myeloid Neoplasms? A Rational Approach
Awada H, Gurnari C, Xie Z, Bewersdorf J, Zeidan A. What’s Next after Hypomethylating Agents Failure in Myeloid Neoplasms? A Rational Approach. Cancers 2023, 15: 2248. PMID: 37190176, PMCID: PMC10137017, DOI: 10.3390/cancers15082248.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsAcute myeloid leukemiaMDS/AML patientsEarly clinical trialsPotential therapeutic agentAML patientsMultidrug combinationsClinical trialsMyeloid leukemiaMyeloid neoplasmsRational approachSingle agentCurrent managementTherapeutic potentialStandardized guidelinesTherapeutic agentsMutational characteristicsPatientsNeoplasmsLatest findingsGenomic factorsCellular adaptationAgentsHMA resistanceFailureLeukemia
2022
Impact of pre-transplant induction and consolidation cycles on AML allogeneic transplant outcomes: a CIBMTR analysis in 3113 AML patients
Boyiadzis M, Zhang M, Chen K, Abdel-Azim H, Abid M, Aljurf M, Bacher U, Badar T, Badawy S, Battiwalla M, Bejanyan N, Bhatt V, Brown V, Castillo P, Cerny J, Copelan E, Craddock C, Dholaria B, Perez M, Ebens C, Gale R, Ganguly S, Gowda L, Grunwald M, Hashmi S, Hildebrandt G, Iqbal M, Jamy O, Kharfan-Dabaja M, Khera N, Lazarus H, Lin R, Modi D, Nathan S, Nishihori T, Patel S, Pawarode A, Saber W, Sharma A, Solh M, Wagner J, Wang T, Williams K, Winestone L, Wirk B, Zeidan A, Hourigan C, Litzow M, Kebriaei P, de Lima M, Page K, Weisdorf D. Impact of pre-transplant induction and consolidation cycles on AML allogeneic transplant outcomes: a CIBMTR analysis in 3113 AML patients. Leukemia 2022, 37: 1006-1017. PMID: 36310182, PMCID: PMC10148918, DOI: 10.1038/s41375-022-01738-3.Peer-Reviewed Original ResearchConceptsPrimary induction failureAllo-HCTRIC allo-HCTComplete remissionOverall survivalConsolidation therapyAML patientsDetectable MRDRelapse riskInduction cyclesAllogeneic hematopoietic cell transplantationConsolidation cyclesPre-transplant inductionFirst complete remissionAdult AML patientsReduced-intensity conditioningBetter overall survivalHematopoietic cell transplantationRisk of relapseAllogeneic transplant outcomesCIBMTR analysisImproved OSInduction failureTransplant outcomesCell transplantationVenetoclax-based salvage therapy in patients with relapsed/refractory acute myeloid leukemia previously treated with FLT3 or IDH1/2 inhibitors
Bewersdorf JP, Shallis RM, Derkach A, Goldberg AD, Stein A, Stein EM, Marcucci G, Zeidan AM, Shimony S, DeAngelo DJ, Stone RM, Aldoss I, Ball BJ, Stahl M. Venetoclax-based salvage therapy in patients with relapsed/refractory acute myeloid leukemia previously treated with FLT3 or IDH1/2 inhibitors. Leukemia & Lymphoma 2022, 64: 188-196. PMID: 36287540, PMCID: PMC9905301, DOI: 10.1080/10428194.2022.2136952.Peer-Reviewed Original ResearchConceptsAcute myeloid leukemiaSalvage therapyIDH1/2 inhibitorsIDH2 inhibitorsMyeloid leukemiaResponse rateRefractory acute myeloid leukemiaEffective salvage therapyLow-dose cytarabineMedian overall survivalRetrospective cohort studyOverall response rateLow response rateCohort studyOverall survivalAML patientsTreatment optionsFLT3 inhibitorsITD mutationPatientsTherapyFLT3Little dataVenetoclaxInhibitors
2021
Predictive Biomarkers of Response to the Polo-like Kinase 1 (PLK1) Inhibitor, Onvansertib, in Combination with Decitabine in Relapsed or Refractory Acute Myeloid Leukemia (R/R AML)
Zeidan A, Ridinger M, Croucher P, Samuëlsz E, Erlander M, Ruffner K, Wang E. Predictive Biomarkers of Response to the Polo-like Kinase 1 (PLK1) Inhibitor, Onvansertib, in Combination with Decitabine in Relapsed or Refractory Acute Myeloid Leukemia (R/R AML). Blood 2021, 138: 3431. DOI: 10.1182/blood-2021-145129.Peer-Reviewed Original ResearchClinical Trials CommitteeCurrent equity holderR AML patientsClinical responseTrials CommitteeGene expression signaturesSpeakers bureauAML patientsSingle agentMulticenter phase 2 studyPhase 1b/2 clinical trialRefractory acute myeloid leukemiaData Safety Monitoring CommitteeAdvisory CommitteeDaiichi SankyoSF mutationsCR/CRiPhase 2 studySafety Monitoring CommitteeChronic myelomonocytic leukemiaCycles of treatmentExpression signaturesComplete hematologic recoveryAcute myeloid leukemiaBone marrow samplesAcute Myeloid Leukemia Leading to Central Diabetes Insipidus
Wojeck B, Gossmann M, Zeidan A, Inzucchi S. Acute Myeloid Leukemia Leading to Central Diabetes Insipidus. Journal Of The Endocrine Society 2021, 5: a570-a571. PMCID: PMC8090637, DOI: 10.1210/jendso/bvab048.1163.Peer-Reviewed Original ResearchCentral diabetes insipidusAcute myeloid leukemiaLeukemic infiltrationMonosomy 7Antidiuretic hormoneWhite blood cell countEVI-1 overexpressionBlood cell countAML patientsAML casesHypothalamic secretionMyeloid leukemiaDiabetes insipidusCell countPituitary glandNormal plateletsPatientsMolecular evaluationInfiltrationOverexpressionComplicationsAnemiaInsipidusLeukemiaAbnormalities
2020
Comparison of Gilteritinib and Salvage Chemotherapy in FLT3-Mutated Acute Myeloid Leukemia on the Number Needed to Treat for Various Clinical Outcomes: A Secondary Analysis of the Admiral Trial
Pandya B, Qi C, Yang H, Garnham A, Shah M, Zeidan A. Comparison of Gilteritinib and Salvage Chemotherapy in FLT3-Mutated Acute Myeloid Leukemia on the Number Needed to Treat for Various Clinical Outcomes: A Secondary Analysis of the Admiral Trial. Blood 2020, 136: 7. DOI: 10.1182/blood-2020-136184.Peer-Reviewed Original ResearchCR/CRhAcute myeloid leukemiaSalvage chemotherapyADMIRAL trialOverall survivalAML patientsClinical benefitMore patientsSurvival outcomesMyeloid leukemiaAstellas PharmaComplete remission/complete remissionConfidence intervalsTyrosine kinase 3 mutationsLonger median overall survivalDismal survival outcomesIncomplete hematologic recoveryIncomplete platelet recoveryMedian overall survivalSuperior clinical benefitSignificant clinical benefitAbsolute rate differenceSelective FLT3 inhibitorHigh response rateEvent rate differenceStreamline - Retrospective Cohort Study of Relapsed or Refractory (R/R) FLT3-Mutated Acute Myeloid Leukemia (AML): Real-World Treatment, Testing Patterns, and Outcomes
Zeidan A, Gilligan A, Gautam S, Grinblatt D, Elsouda D, Sullivan L, Pandya B. Streamline - Retrospective Cohort Study of Relapsed or Refractory (R/R) FLT3-Mutated Acute Myeloid Leukemia (AML): Real-World Treatment, Testing Patterns, and Outcomes. Blood 2020, 136: 30-31. DOI: 10.1182/blood-2020-136366.Peer-Reviewed Original ResearchFLT3 tyrosine kinase inhibitorsAcute myeloid leukemiaTyrosine kinase inhibitorsMedian overall survivalOverall survivalFLT3 mutation statusTreatment patternsR settingTKI useAML patientsFMS-like tyrosine kinase 3 (FLT3) mutationsMutation statusDiagnosis of AMLTyrosine kinase 3 mutationsElectronic medical record dataEligible adult patientsHigh-intensity chemotherapyOngoing retrospective studyPost-treated patientsAstellas PharmaRetrospective cohort studySystemic anticancer therapyKaplan-Meier analysisReal-world treatmentTesting trendsBlast 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 outcomesPhase 1 dose escalation trial of volasertib in combination with decitabine in patients with acute myeloid leukemia
Cortes J, Podoltsev N, Kantarjian H, Borthakur G, Zeidan AM, Stahl M, Taube T, Fagan N, Rajeswari S, Uy GL. Phase 1 dose escalation trial of volasertib in combination with decitabine in patients with acute myeloid leukemia. International Journal Of Hematology 2020, 113: 92-99. PMID: 32951163, DOI: 10.1007/s12185-020-02994-8.Peer-Reviewed Original ResearchMeSH KeywordsAgedAntineoplastic Combined Chemotherapy ProtocolsCell Cycle ProteinsDecitabineDose-Response Relationship, DrugFebrile NeutropeniaFeeding and Eating DisordersFemaleGene ExpressionHumansLeukemia, Myeloid, AcuteMaleMolecular Targeted TherapyProtein Serine-Threonine KinasesProto-Oncogene ProteinsPteridinesTreatment OutcomeConceptsAcute myeloid leukemiaMyeloid leukemiaCommon treatment-emergent adverse eventsPhase 1 dose-escalation trialTreatment-emergent adverse eventsMTD of volasertibObjective response rateAdverse event profileDose-escalation trialPhase 1 trialAnti-leukemic activityPolo-like kinase 1Febrile neutropeniaEscalation trialAdverse eventsCell cycle kinase inhibitorsAML patientsEvent profilePoor prognosisResponse ratePatientsVolasertibDecitabineKinase inhibitorsNumerous cancersClinical outcomes of older patients with AML receiving hypomethylating agents: a large population-based study in the United States
Zeidan AM, Wang R, Wang X, Shallis RM, Podoltsev NA, Bewersdorf JP, Huntington SF, Neparidze N, Giri S, Gore SD, Davidoff AJ, Ma X. Clinical outcomes of older patients with AML receiving hypomethylating agents: a large population-based study in the United States. Blood Advances 2020, 4: 2192-2201. PMID: 32433746, PMCID: PMC7252544, DOI: 10.1182/bloodadvances.2020001779.Peer-Reviewed Original ResearchConceptsAcute myeloid leukemiaDecitabine-treated patientsTransfusion independenceRed blood cell transfusion independenceLarge population-based studyOlder AML patientsRBC transfusion independenceEnd Results-MedicarePopulation-based studyStandard of careAgent azacitidineMedian survivalOlder patientsIntensive therapyAML patientsClinical outcomesClinical benefitMyeloid leukemiaMortality riskPatientsAzacitidineDecitabineOlder adultsOne-thirdMeaningful differencesPatterns of care and clinical outcomes with cytarabine-anthracycline induction chemotherapy for AML patients in the United States
Zeidan AM, Podoltsev NA, Wang X, Zhang C, Bewersdorf JP, Shallis RM, Huntington SF, Neparidze N, Giri S, Gore SD, Davidoff AJ, Ma X, Wang R. Patterns of care and clinical outcomes with cytarabine-anthracycline induction chemotherapy for AML patients in the United States. Blood Advances 2020, 4: 1615-1623. PMID: 32311013, PMCID: PMC7189301, DOI: 10.1182/bloodadvances.2020001728.Peer-Reviewed Original ResearchConceptsIntensive induction chemotherapyAcute myeloid leukemiaHospital deathInduction chemotherapyAdult patientsMultivariable logistic regression modelLow hospital volumePremier Healthcare DatabasePredictors of deathHealthcare resource utilizationIntensive care unitPatterns of careStandard of careLogistic regression modelsFit patientsRemission inductionFirst hospitalizationHospital volumeInpatient deathInpatient mortalityOlder patientsSupportive careMedian ageAML patientsCare unit
2019
1066O Polo-like kinase 1 (PLK1) inhibitor, onvansertib, in combination with low-dose cytarabine or decitabine in patients with relapsed/refractory acute myeloid leukaemia in phase Ib
Zeidan A, Becker P, Patel P, Schiller G, Tsai M, Lin T, Wang E, Erlander M, Cortes J. 1066O Polo-like kinase 1 (PLK1) inhibitor, onvansertib, in combination with low-dose cytarabine or decitabine in patients with relapsed/refractory acute myeloid leukaemia in phase Ib. Annals Of Oncology 2019, 30: v435. DOI: 10.1093/annonc/mdz251.001.Peer-Reviewed Original ResearchTarget engagementEvaluable ptsHigh dosesRefractory acute myeloid leukemiaInhibition of PLK1CR/CRiLow-dose cytarabinePreclinical AML modelsR AML patientsDose-escalation phasePolo-like kinase 1Anti-leukaemic activityAcute myeloid leukemiaEvaluable patientsLDAC armBM blastsDose escalationAML patientsPolo-like kinase 1 inhibitorsEscalation phaseBiomarker statusMyeloid leukemiaSelective PLK1 inhibitorBlood samplesHigh dose
2018
Outcomes 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 patients