2024
Pre-emptive therapeutic decisions based on measurable residual disease status in acute myeloid leukemia: ready for prime time?
El Chaer F, Perissinotti A, Loghavi S, Zeidan A. Pre-emptive therapeutic decisions based on measurable residual disease status in acute myeloid leukemia: ready for prime time? Leukemia 2024, 1-7. PMID: 39496917, DOI: 10.1038/s41375-024-02458-6.Peer-Reviewed Original ResearchAcute myeloid leukemiaMyeloid leukemiaCore binding factor acute myeloid leukemiaIncreased risk of relapseResidual disease statusPost-allo-HCTHematopoietic cell transplantationRisk of relapseTherapeutic decision-makingInnovative treatment strategiesMRD-positiveIntensive chemotherapyMRD monitoringCell transplantationNPM1 mutationsImprove patient outcomesRisk stratificationTherapeutic decisionsTreatment strategiesIncreased riskRisk factorsMRDNatural historyPreemptive interventionAssess diseaseAcute myeloid leukemia (AML) with chromosome 3 inversion: biology, management, and clinical outcome
Alhajahjeh A, Bewersdorf J, Bystrom R, Zeidan A, Shimony S, Stahl M. Acute myeloid leukemia (AML) with chromosome 3 inversion: biology, management, and clinical outcome. Leukemia & Lymphoma 2024, 65: 1541-1551. PMID: 38962996, DOI: 10.1080/10428194.2024.2367040.Peer-Reviewed Original ResearchAcute myeloid leukemiaIntensive chemotherapyHypomethylating agentsMyeloid leukemiaAllogeneic stem cell transplantationAcute myeloid leukemia casesAcute myeloid leukemia subtypesStem cell transplantationComplex hematological malignancyCurrent treatment modalitiesRare genetic anomalyCell transplantationHematologic malignanciesTreatment modalitiesClinical outcomesTreatment responseInv(3Genetic alterationsLeukemia developmentTreatment strategiesCellular processesGenetic anomaliesLeukemiaFusion geneClinical implicationsTreatment of Myelodysplastic Syndromes for Older Patients: Current State of Science, Challenges, and Opportunities
Kewan T, Stahl M, Bewersdorf J, Zeidan A. Treatment of Myelodysplastic Syndromes for Older Patients: Current State of Science, Challenges, and Opportunities. Current Hematologic Malignancy Reports 2024, 19: 138-150. PMID: 38632155, DOI: 10.1007/s11899-024-00733-y.Peer-Reviewed Original ResearchHematopoietic stem cell transplantationAllogeneic hematopoietic stem cell transplantationLower-risk MDSErythropoiesis-stimulating agentsHypomethylating agentsIPSS-MHR-MDSRisk stratificationMolecular International Prognostic Scoring SystemRisk of leukemia progressionTreated with hypomethylating agentsInternational Prognostic Scoring SystemTreatment of myelodysplastic syndromesOral hypomethylating agentsHigh-risk MDSPrognostic Scoring SystemStem cell transplantationEnhanced risk stratificationRecent FindingsRecent advancesRefine treatment strategiesQuality-of-life improvementAssociated with treatmentTreatment decision-makingIntensive chemotherapyMDS patients
2023
Management of Acute Myeloid Leukemia with Myelodysplasia-Related Changes and Therapy-Related Acute Myeloid Leukemia
Bewersdorf J, Zeidan A. Management of Acute Myeloid Leukemia with Myelodysplasia-Related Changes and Therapy-Related Acute Myeloid Leukemia. 2023, 119-128. DOI: 10.1007/978-981-99-3810-0_8.ChaptersTherapy-related AMLAcute myeloid leukemiaSecondary AMLAML-MRCMyeloid leukemiaRandomized phase III clinical trialsPhase III clinical trialsAdverse cytogenetic featuresOverall survival benefitDe novo AMLT-AML patientsYears of ageHigh-risk mutationsInduction chemotherapyMonosomal karyotypeCPX-351Intensive chemotherapyNovo AMLSurvival benefitTreatment landscapeAdverse prognosisFrontline treatmentSubgroup analysisClinical trialsConventional chemotherapyVenetoclax plus azacitidine compared with intensive chemotherapy as induction for patients with acute myeloid leukemia: retrospective analysis of an electronic medical record database in the United States
Zeidan A, Pollyea D, Borate U, Vasconcelos A, Potluri R, Rotter D, Kiendrebeogo Z, Gaugler L, Prebet T, Strocchia M, Bonifacio G, Chen C. Venetoclax plus azacitidine compared with intensive chemotherapy as induction for patients with acute myeloid leukemia: retrospective analysis of an electronic medical record database in the United States. Annals Of Hematology 2023, 102: 749-754. PMID: 36732419, PMCID: PMC10285011, DOI: 10.1007/s00277-023-05109-5.Peer-Reviewed Original ResearchConceptsHematopoietic stem cell transplantAcute myeloid leukemiaRelapse-free survivalIntensive chemotherapyComplete remissionOverall survivalMyeloid leukemiaRetrospective analysisMedian relapse-free survivalElectronic medical record databaseFlatiron Health databaseMedian overall survivalStem cell transplantMedical record databaseElectronic health recordsHSCT ratesRelapse rateCell transplantControlled TrialsTreatment outcomesHealth databasesPatientsRecord databaseMonthsHealth records
2022
TP53-altered higher-risk myelodysplastic syndromes/neoplasms and acute myeloid leukemia: a distinct genetic entity with unique unmet needs
Ball S, Loghavi S, Zeidan A. TP53-altered higher-risk myelodysplastic syndromes/neoplasms and acute myeloid leukemia: a distinct genetic entity with unique unmet needs. Leukemia & Lymphoma 2022, 64: 540-550. PMID: 36323304, DOI: 10.1080/10428194.2022.2136969.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsAcute myeloid leukemiaMyelodysplastic syndromeVariant allele frequencyMyeloid leukemiaMDS/acute myeloid leukemiaIndependent poor prognostic factorBCL2 inhibitor venetoclaxPoor prognostic factorDisease-modifying therapiesIntensive chemotherapyBlast countClinical coursePrognostic factorsInvestigational agentsDisease entityClinical studiesInhibitor venetoclaxMyeloid neoplasmsResponse ratePathogenic alterationsNeoplasmsDistinct genetic entitiesLeukemiaGenetic characteristicsAllele frequenciesAML-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 1MDS-476 Sabatolimab (MBG453) Combination Treatment Regimens for Patients With Higher-Risk Myelodysplastic Syndromes (HR-MDS): The Myelodysplastic Syndromes Studies in the STIMULUS Immuno-Myeloid Clinical Trial Program
Zeidan A, Al-Kali A, Borate U, Cluzeau T, DeZern A, Esteve J, Giagounidis A, Kobata K, Lyons R, Platzbecker U, Sallman D, Santini V, Sanz G, Sekeres M, Wei A, Xiao Z, Van Hoef M, Nourry-Boulot C, Sadek I, Ma F, Iordan A, Sabo J, Garcia-Manero G. MDS-476 Sabatolimab (MBG453) Combination Treatment Regimens for Patients With Higher-Risk Myelodysplastic Syndromes (HR-MDS): The Myelodysplastic Syndromes Studies in the STIMULUS Immuno-Myeloid Clinical Trial Program. Clinical Lymphoma Myeloma & Leukemia 2022, 22: s317. DOI: 10.1016/s2152-2650(22)01420-3.Peer-Reviewed Original ResearchHematopoietic stem cell transplantLeukemia-free survivalPhase II trialHigh-risk myelodysplastic syndromeHR-MDS patientsClinical trial programII trialLeukemic stem cellsCombination therapyTim-3Trial programLeukemic cellsTransfusion-free intervalEvent-free survivalPhase III trialsStem cell transplantOverall response rateEarly phase trialsNovartis Pharmaceuticals CorporationImprovement of fatigueExpansion cohortIntensive chemotherapyPrimary endpointDurable responsesIII trialsProspective comparison of outcomes with azacitidine and decitabine in patients with AML ineligible for intensive chemotherapy
Zeidan AM, Fenaux P, Gobbi M, Mayer J, Roboz GJ, Krauter J, Robak T, Kantarjian HM, Novák J, Jedrzejczak WW, Thomas X, Ojeda-Uribe M, Miyazaki Y, Min YH, Yeh SP, Brandwein JM, Gercheva L, Demeter J, Griffiths EA, Yee KWL, Issa JJ, Bewersdorf JP, Keer H, Hao Y, Azab M, Döhner H. Prospective comparison of outcomes with azacitidine and decitabine in patients with AML ineligible for intensive chemotherapy. Blood 2022, 140: 285-289. PMID: 35507690, PMCID: PMC9305088, DOI: 10.1182/blood.2022015832.Peer-Reviewed Original ResearchP570: REAL-WORLD EFFICACY OUTCOMES OF VENETOCLAX PLUS AZACITIDINE VS INTENSIVE CHEMOTHERAPY FOR INDUCTION THERAPY IN ADULT PATIENTS WITH ACUTE MYELOID LEUKEMIA
Zeidan A, Pollyea D, Borate U, Vasconcelos A, Potluri R, Rotter D, Kiendrebeogo Z, Gaugler L, Bonifacio G, Prebet T, Chen C. P570: REAL-WORLD EFFICACY OUTCOMES OF VENETOCLAX PLUS AZACITIDINE VS INTENSIVE CHEMOTHERAPY FOR INDUCTION THERAPY IN ADULT PATIENTS WITH ACUTE MYELOID LEUKEMIA. HemaSphere 2022, 6: 469-470. DOI: 10.1097/01.hs9.0000845168.01159.c0.Peer-Reviewed Original ResearchA phase 1b study of glasdegib + azacitidine in patients with untreated acute myeloid leukemia and higher-risk myelodysplastic syndromes
Sekeres MA, Schuster M, Joris M, Krauter J, Maertens J, Breems D, Gyan E, Kovacsovics T, Verma A, Vyas P, Wang ES, Ching K, O’Brien T, Gallo Stampino C, Ma WW, Kudla A, Chan G, Zeidan AM. A phase 1b study of glasdegib + azacitidine in patients with untreated acute myeloid leukemia and higher-risk myelodysplastic syndromes. Annals Of Hematology 2022, 101: 1689-1701. PMID: 35488900, DOI: 10.1007/s00277-022-04853-4.Peer-Reviewed Original ResearchConceptsAcute myeloid leukemiaHigh-risk myelodysplastic syndromePhase 1b studyChronic myelomonocytic leukemiaMyelodysplastic syndromeExpansion cohortSafety profileMDS cohortMyeloid leukemiaTreatment-emergent adverse eventsUntreated acute myeloid leukemiaNon-hematologic gradeMedian overall survivalAcceptable safety profileOverall response rateDrug-drug interactionsSafety cohortIntensive chemotherapyAdverse eventsOverall survivalClinical benefitQT prolongationAML cohortMyelomonocytic leukemiaGlasdegib
2021
The Current Understanding of and Treatment Paradigm for Newly-Diagnosed TP53-Mutated Acute Myeloid Leukemia
Shallis R, Stahl M, Bewersdorf J, Zeidan A. The Current Understanding of and Treatment Paradigm for Newly-Diagnosed TP53-Mutated Acute Myeloid Leukemia. Hemato 2021, 2: 748-763. DOI: 10.3390/hemato2040051.Peer-Reviewed Original ResearchAcute myeloid leukemiaMyeloid leukemiaTherapy-related acute myeloid leukemiaMeasurable residual disease statusHematopoietic stem cell transplantationMedian overall survivalResidual disease statusStem cell transplantationCurrent treatment approachesIntensive chemotherapyIntensive regimensRemission rateCytogenetic riskOverall survivalWorse prognosisCell transplantationConditioning intensityTreatment paradigmTreatment approachesTP53 mutationsDisease statusBiological subsetsPatientsPrognosisLeukemiaTreatment Utilization and Characteristics Among Patients with Higher-Risk Myelodysplastic Syndromes According to Hypomethylating Agent Use
Zeidan A, Divino V, DeKoven M, Shah D, Wang E, Bey D, Salimi T, Epstein R. Treatment Utilization and Characteristics Among Patients with Higher-Risk Myelodysplastic Syndromes According to Hypomethylating Agent Use. Blood 2021, 138: 5030. DOI: 10.1182/blood-2021-144852.Peer-Reviewed Original ResearchHigh-risk myelodysplastic syndromeClinical Trials CommitteeHigher comorbidity burdenHMA therapySupportive careTrials CommitteeComorbidity burdenTreatment utilizationMean ageMyelodysplastic syndromeReal-world clinical practiceBaseline renal diseaseIntra-Cellular TherapiesLower comorbidity burdenAbsence of progressionRetrospective observational studyStem cell transplantationSimilar mean ageReal-world studyCurrent employmentFrailer patientsIQVIA PharMetricsSubcutaneous azacitidineIndex dateIntensive chemotherapySabatolimab (MBG453) Combination Treatment Regimens for Patients (Pts) with Higher-Risk Myelodysplastic Syndromes (HR-MDS): The MDS Studies in the Stimulus Immuno-Myeloid Clinical Trial Program
Zeidan A, Al-Kali A, Borate U, Cluzeau T, DeZern A, Esteve J, Giagounidis A, Kobata K, Lyons R, Platzbecker U, Sallman D, Santini V, Sanz G, Sekeres M, Wei A, Xiao Z, Van Hoef M, Nourry-Boulot C, Sadek I, Bengoudifa B, Sachs C, Sabo J, Garcia-Manero G. Sabatolimab (MBG453) Combination Treatment Regimens for Patients (Pts) with Higher-Risk Myelodysplastic Syndromes (HR-MDS): The MDS Studies in the Stimulus Immuno-Myeloid Clinical Trial Program. Blood 2021, 138: 4669. DOI: 10.1182/blood-2021-145626.Peer-Reviewed Original ResearchHigh-risk myelodysplastic syndromeClinical Trials CommitteeProgression-free survivalHematopoietic stem cell transplantLeukemia-free survivalClinical trial programLeukemic stem cellsComplete responsePrimary endpointOverall survivalTim-3Trials CommitteeHMA therapySecondary endpointsII trialAdverse eventsNovartis Pharma AGCombination therapyMyeloid malignanciesTrial programSpeakers bureauBristol-Myers SquibbIntensive chemotherapyPartial remissionTarget enrollmentHealth-Related Quality of Life (HRQoL) during Treatment with Enasidenib (ENA) Plus Azacitidine (AZA) in Patients with Newly Diagnosed Mutant IDH2 (m IDH2) Acute Myeloid Leukemia (AML) Not Eligible for Intensive Chemotherapy (IC)
DiNardo C, Dohner H, Zeidan A, Schuh A, Vyas P, Stein E, Wei A, de Botton S, Chen C, Lord-Bessen J, Martin-Regueira P, Lersch F, Gong J, Guo S, Shi L, Montesinos P. Health-Related Quality of Life (HRQoL) during Treatment with Enasidenib (ENA) Plus Azacitidine (AZA) in Patients with Newly Diagnosed Mutant IDH2 (m IDH2) Acute Myeloid Leukemia (AML) Not Eligible for Intensive Chemotherapy (IC). Blood 2021, 138: 1244. DOI: 10.1182/blood-2021-147601.Peer-Reviewed Original ResearchClinical Trials CommitteeAcute myeloid leukemiaEQ-5D VASQLQ-C30 domainsCurrent equity holderBristol-Myers SquibbGHS/QoLGlobal health statusOverall response rateTrials CommitteeQLQ-C30 scoresEQ-5DIntensive chemotherapyPhysical functioningRole functioningDaiichi SankyoSpeakers bureauEvaluable ptsBristol-Myers Squibb CompanyHRQoL scoresDyspnea domainEQ-5D visual analog scale scoresJazz PharmaceuticalsMeaningful improvementsVisual analog scale scoreVenetoclax Plus Azacitidine (VEN-AZA) Vs. Intensive Chemotherapy (IC) As Induction for Patients with Acute Myeloid Leukemia (AML): Retrospective Analysis of an Electronic Medical Records (EMR) Database in the United States
Zeidan A, Pollyea D, Borate U, Vasconcelos A, Potluri R, Rotter D, Kiendrebeogo Z, Gaugler L, Bonifacio G, Chen C. Venetoclax Plus Azacitidine (VEN-AZA) Vs. Intensive Chemotherapy (IC) As Induction for Patients with Acute Myeloid Leukemia (AML): Retrospective Analysis of an Electronic Medical Records (EMR) Database in the United States. Blood 2021, 138: 277. DOI: 10.1182/blood-2021-147926.Peer-Reviewed Original ResearchClinical Trials CommitteeRelapse-free survivalAcute myeloid leukemiaMedian relapse-free survivalCurrent equity holderElectronic medical record databaseBristol-Myers SquibbSubgroups of ptsIntensive chemotherapyIC cohortStart of therapyOverall survivalTrials CommitteeMedical record databaseRemission rateCR rateAge-based subgroupsYears subgroupRecord databaseIncomplete hematologic recovery (CRi) ratesReal-world clinical practicePhase 3 trial dataAdvisory CommitteeDaiichi SankyoGood remission rate
2020
The STIMULUS Program: Clinical Trials Evaluating Sabatolimab (MBG453) Combination Therapy in Patients (Pts) with Higher-Risk Myelodysplastic Syndromes (HR-MDS) or Acute Myeloid Leukemia (AML)
Zeidan A, Esteve J, Giagounidis A, Kim H, Miyazaki Y, Platzbecker U, Schuh A, Sekeres M, Westermann J, Xiao Z, Malek K, Scott J, Niolat J, Peyrard S, Ma F, Kiertsman F, Stegert M, Hertle S, Fenaux P, Santini V. The STIMULUS Program: Clinical Trials Evaluating Sabatolimab (MBG453) Combination Therapy in Patients (Pts) with Higher-Risk Myelodysplastic Syndromes (HR-MDS) or Acute Myeloid Leukemia (AML). Blood 2020, 136: 45-46. DOI: 10.1182/blood-2020-134718.Peer-Reviewed Original ResearchHigh-risk myelodysplastic syndromeHematopoietic stem cell transplantationAcute myeloid leukemiaEvent-free survivalLeukemic stem cellsIntensive chemotherapyOverall survivalPrimary endpointSecondary endpointsCurrent equity holderEligible ptsTim-3Transfusion independenceCombination therapyEastern Cooperative Oncology Group performance statusCR/CRi rateEncouraging overall response rateAdvisory CommitteeDaiichi SankyoDuration of CRTransfusion-free intervalLeukemia-free survivalComplete remission rateHigh-risk MDSProgression-free survivalBlast 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 outcomesAML-205: Health-Related Quality of Life in Patients with Untreated Higher-Risk Myelodysplastic Syndromes, Acute Myeloid Leukemia, and Chronic Myelomonocytic Leukemia Receiving Glasdegib + Azacitidine
Wang E, Bell T, Zeidan A, Bhattcharyya H, Kudla A, Chan G, Sekeres M. AML-205: Health-Related Quality of Life in Patients with Untreated Higher-Risk Myelodysplastic Syndromes, Acute Myeloid Leukemia, and Chronic Myelomonocytic Leukemia Receiving Glasdegib + Azacitidine. Clinical Lymphoma Myeloma & Leukemia 2020, 20: s191. DOI: 10.1016/s2152-2650(20)30732-1.Peer-Reviewed Original ResearchHigh-risk myelodysplastic syndromeAcute myeloid leukemiaChronic myelomonocytic leukemiaPatient Global ImpressionMyelodysplastic syndromeIntensive chemotherapyPatient's impressionGlobal ImpressionAML cohortMDS cohortMyeloid leukemiaAML/myelodysplastic syndromeMD Anderson Symptom InventoryFirst-line treatment optionLower symptom burdenHRQoL of patientsOpen-label studyHealth-related qualityPatient-reported outcomesEnd of treatmentMain outcome measuresTotal symptom severityQuality of lifeTrend of improvementStudy medication