2023
Traditional Medicare or Medicare Advantage? The Leukemia and Cancer Perspective
Kantarjian H, Zeidan A, Fathi A, Stein E, Rajkumar V, Tefferi A. Traditional Medicare or Medicare Advantage? The Leukemia and Cancer Perspective. Mayo Clinic Proceedings 2023, 99: 15-21. PMID: 38108685, DOI: 10.1016/j.mayocp.2023.11.004.Peer-Reviewed Original ResearchSabatolimab plus hypomethylating agents in previously untreated patients with higher-risk myelodysplastic syndromes (STIMULUS-MDS1): a randomised, double-blind, placebo-controlled, phase 2 trial
Zeidan A, Ando K, Rauzy O, Turgut M, Wang M, Cairoli R, Hou H, Kwong Y, Arnan M, Meers S, Pullarkat V, Santini V, Malek K, Kiertsman F, Niolat J, Ramos P, Menssen H, Fenaux P, Miyazaki Y, Platzbecker U. Sabatolimab plus hypomethylating agents in previously untreated patients with higher-risk myelodysplastic syndromes (STIMULUS-MDS1): a randomised, double-blind, placebo-controlled, phase 2 trial. The Lancet Haematology 2023, 11: e38-e50. PMID: 38065203, DOI: 10.1016/s2352-3026(23)00333-2.Peer-Reviewed Original ResearchConceptsHigh-risk myelodysplastic syndromeProgression-free survivalComplete response rateMyelodysplastic syndromePlacebo groupPrimary endpointUntreated patientsAdverse eventsComplete responseResponse rateImmune-mediated adverse eventsMedian progression-free survivalRandomised phase 3 trialT-cell immunoglobulin domainFinal data cutoffTreatment-related deathsCommon adverse eventsFull analysis setMucin domain 3Phase 2 studyPhase 2 trialPhase 3 trialLeukaemic stem cellsFebrile neutropeniaData cutoffStatin use, survival and incidence of thrombosis among older patients with polycythemia vera and essential thrombocythemia
Podoltsev N, Wang R, Shallis R, Stempel J, Di M, Neparidze N, Zeidan A, Huntington S, Giri S, Hull S, Gore S, Ma X. Statin use, survival and incidence of thrombosis among older patients with polycythemia vera and essential thrombocythemia. Cancer Medicine 2023, 12: 18889-18900. PMID: 37702132, PMCID: PMC10557879, DOI: 10.1002/cam4.6528.Peer-Reviewed Original ResearchConceptsIncidence of thrombosisPolycythemia veraEssential thrombocythemiaStatin useOlder adultsEnd Results-Medicare databasePopulation-based cohort studyArterial thrombotic eventsSurvival of patientsUse of statinsClaims-based studyRisk of thrombosisCardiovascular morbidityCause mortalityTreatment weighting (IPTW) approachCohort studyOlder patientsOverall survivalThrombotic eventsVenous thrombosisPatient populationPrevious registryStatinsTherapeutic strategiesET subgroupOlder patients with chronic myeloid leukemia face suboptimal molecular testing and tyrosine kinase inhibitor adherence
Shallis R, Wang R, Zeidan A, Huntington S, Neparidze N, Stempel J, Mendez L, Di M, Ma X, Podoltsev N. Older patients with chronic myeloid leukemia face suboptimal molecular testing and tyrosine kinase inhibitor adherence. Blood Advances 2023, 7: 3213-3224. PMID: 36939371, PMCID: PMC10338212, DOI: 10.1182/bloodadvances.2022009074.Peer-Reviewed Original ResearchConceptsChronic myeloid leukemiaTKI adherenceTKI initiationOlder patientsMyeloid leukemiaEnd Results-Medicare databaseTyrosine kinase inhibitor usePolymerase chain reaction testingQuantitative polymerase chain reaction testingOlder patient populationCare of patientsHealth care accessReal-world studyReal-world evidenceLow socioeconomic statusLow-income subsidyFirst yearInfluenza vaccinationInhibitor useWorse survivalTKI treatmentMultivariable analysisPatient populationOptimal monitoringCare accessEfficacy and safety of luspatercept versus epoetin alfa in erythropoiesis-stimulating agent-naive, transfusion-dependent, lower-risk myelodysplastic syndromes (COMMANDS): interim analysis of a phase 3, open-label, randomised controlled trial
Platzbecker U, Della Porta M, Santini V, Zeidan A, Komrokji R, Shortt J, Valcarcel D, Jonasova A, Dimicoli-Salazar S, Tiong I, Lin C, Li J, Zhang J, Giuseppi A, Kreitz S, Pozharskaya V, Keeperman K, Rose S, Shetty J, Hayati S, Vodala S, Prebet T, Degulys A, Paolini S, Cluzeau T, Fenaux P, Garcia-Manero G. Efficacy and safety of luspatercept versus epoetin alfa in erythropoiesis-stimulating agent-naive, transfusion-dependent, lower-risk myelodysplastic syndromes (COMMANDS): interim analysis of a phase 3, open-label, randomised controlled trial. The Lancet 2023, 402: 373-385. PMID: 37311468, DOI: 10.1016/s0140-6736(23)00874-7.Peer-Reviewed Original ResearchConceptsLower-risk myelodysplastic syndromesRed blood cell transfusion independenceEpoetin alfa groupErythropoiesis-stimulating agentsEpoetin alfaMyelodysplastic syndromeInterim analysisPrimary endpointAdverse eventsAlfa groupTransfusion independenceLower riskBody weightTreatment-emergent adverse eventsTreatment-related adverse eventsRed blood cell transfusionDurable clinical efficacyMean hemoglobin increaseMedian treatment exposureBlood cell transfusionCOVID-19 pneumoniaSubgroup of patientsWeeks of treatmentTreatment of anemiaAcute myeloid leukemiaSecond malignancies among older patients with classical myeloproliferative neoplasms treated with hydroxyurea
Wang R, Shallis R, Stempel JM, Huntington SF, Zeidan AM, Gore SD, Ma X, Podoltsev NA. Second malignancies among older patients with classical myeloproliferative neoplasms treated with hydroxyurea. Blood Advances 2023, 7: 734-743. PMID: 35917456, PMCID: PMC9989521, DOI: 10.1182/bloodadvances.2022008259.Peer-Reviewed Original ResearchConceptsSecond malignanciesAcute myeloid leukemiaOlder patientsMyelodysplastic syndromeMyeloproliferative neoplasmsHU usersHigh riskPolycythemia veraEssential thrombocythemiaRisk of SMAML/myelodysplastic syndromeClassical Philadelphia chromosome-negative myeloproliferative neoplasmsImpact of hydroxyureaRetrospective cohort studyUse of hydroxyureaPhiladelphia chromosome-negative myeloproliferative neoplasmsClassical myeloproliferative neoplasmsCumulative incidence probabilityCohort studyCytoreductive therapyPatient characteristicsMedian ageHU useMyeloid leukemiaSecondary myelofibrosisTreatment patterns and real-world effectiveness of rituximab maintenance in older patients with mantle cell lymphoma: a population-based analysis
Di M, Long J, Kothari S, Sethi T, Zeidan A, Podoltsev N, Shallis R, Wang R, Ma X, Huntington S. Treatment patterns and real-world effectiveness of rituximab maintenance in older patients with mantle cell lymphoma: a population-based analysis. Haematologica 2023, 108: 2218-2223. PMID: 36655436, PMCID: PMC10388284, DOI: 10.3324/haematol.2022.282252.Peer-Reviewed Original Research
2022
Evaluating complete remission with partial hematologic recovery (CRh) as a response criterion in myelodysplastic syndromes (MDS)
Brunner A, Gavralidis A, Ali N, Hunter A, Komrokji R, Zeidan A, Sallman D. Evaluating complete remission with partial hematologic recovery (CRh) as a response criterion in myelodysplastic syndromes (MDS). Blood Cancer Journal 2022, 12: 153. PMID: 36379923, PMCID: PMC9666661, DOI: 10.1038/s41408-022-00748-9.Peer-Reviewed Original ResearchConceptsPartial hematologic recoveryMyelodysplastic syndromeHematologic recoveryResponse criteriaCR/CRhIWG 2006 criteriaDuration of therapyBest overall responseTime of therapyCR responseCRH responseDNMTi therapyOS associationComplete remissionMedian OSOverall survivalAdult patientsAllogeneic transplantsMedian ageMDS patientsMultivariable analysisClinical trialsSimilar survivalPatientsTherapyA phase 1b study of venetoclax and azacitidine combination in patients with relapsed or refractory myelodysplastic syndromes
Zeidan AM, Borate U, Pollyea DA, Brunner AM, Roncolato F, Garcia JS, Filshie R, Odenike O, Watson AM, Krishnadasan R, Bajel A, Naqvi K, Zha J, Cheng W, Zhou Y, Hoffman D, Harb JG, Potluri J, Garcia‐Manero G. A phase 1b study of venetoclax and azacitidine combination in patients with relapsed or refractory myelodysplastic syndromes. American Journal Of Hematology 2022, 98: 272-281. PMID: 36309981, PMCID: PMC10100228, DOI: 10.1002/ajh.26771.Peer-Reviewed Original ResearchConceptsMedian overall survivalMyelodysplastic syndromeOverall survivalTransfusion independenceHematological improvementTherapy failureHigh-risk myelodysplastic syndromeInternational Working Group criteriaHematological adverse eventsPhase 1b studyRefractory myelodysplastic syndromeStandard of careEfficacy of venetoclaxEffective therapeutic strategyFebrile neutropeniaMarrow CROral venetoclaxComplete remissionAdverse eventsMedian durationAzacitidine treatmentMedian timeMarrow responseMulticenter studyGroup criteriaPatient Preferences for Benefits, Risks, and Administration Route of Hypomethylating Agents in Myelodysplastic Syndromes
Zeidan AM, Tsai JH, Karimi M, Schmier J, Jayade S, Zormpas E, Hassan A, Ruiters D, Anthony C, Hill K, Wert T, Botteman M. Patient Preferences for Benefits, Risks, and Administration Route of Hypomethylating Agents in Myelodysplastic Syndromes. Clinical Lymphoma Myeloma & Leukemia 2022, 22: e853-e866. PMID: 35729009, DOI: 10.1016/j.clml.2022.04.023.Peer-Reviewed Original ResearchConceptsMyelodysplastic syndromePatient preferencesRelative attribute importanceRisk of AMLPatient advocacy group representativesAdministration burdenLevel of fatigueMode of administrationDCE choice tasksAML transformationMDS patientsSurvey patientsOral pillsCanadian patientsAdvocacy group representativesHypomethylating agentNumber of visitsAdministration frequencyAdministration routePatient proxyPatientsEquivalent effectivenessMDS riskAdministration methodsSame riskImpact of Hypomethylating Agent Use on Hospital and Emergency Room Visits, and Predictors of Early Discontinuation in Patients With Higher-Risk Myelodysplastic Syndromes
Zeidan AM, Joshi N, Kale H, Wang WJ, Corman S, Salimi T, Epstein RS. Impact of Hypomethylating Agent Use on Hospital and Emergency Room Visits, and Predictors of Early Discontinuation in Patients With Higher-Risk Myelodysplastic Syndromes. Clinical Lymphoma Myeloma & Leukemia 2022, 22: 670-679. PMID: 35614009, DOI: 10.1016/j.clml.2022.04.016.Peer-Reviewed Original ResearchConceptsHigh-risk myelodysplastic syndromeHMA therapyPoor performance statusRate of hospitalizationSEER-Medicare databaseMyelodysplastic syndromeER visitsEarly discontinuationPerformance statusEmergency roomOlder agePredictors of discontinuationEmergency room visitsHigh-risk groupHigh economic burdenTreatment discontinuationExcess blastsMore hospitalizationsNew hospitalizationRefractory anemiaRoom visitsHigh riskDiscontinuationMD diagnosisAgent useA 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 rateNeutrophil and platelet increases with luspatercept in lower-risk MDS: secondary endpoints from the MEDALIST trial
Garcia-Manero G, Mufti GJ, Fenaux P, Buckstein R, Santini V, Díez-Campelo M, Finelli C, Ilhan O, Sekeres MA, Zeidan AM, Ito R, Zhang J, Rampersad A, Sinsimer D, Backstrom JT, Platzbecker U, Komrokji RS. Neutrophil and platelet increases with luspatercept in lower-risk MDS: secondary endpoints from the MEDALIST trial. Blood 2022, 139: 624-629. PMID: 34758066, PMCID: PMC8796653, DOI: 10.1182/blood.2021012589.Peer-Reviewed Original ResearchPhase 1 study of anti-CD47 monoclonal antibody CC-90002 in patients with relapsed/refractory acute myeloid leukemia and high-risk myelodysplastic syndromes
Zeidan AM, DeAngelo DJ, Palmer J, Seet CS, Tallman MS, Wei X, Raymon H, Sriraman P, Kopytek S, Bewersdorf JP, Burgess MR, Hege K, Stock W. Phase 1 study of anti-CD47 monoclonal antibody CC-90002 in patients with relapsed/refractory acute myeloid leukemia and high-risk myelodysplastic syndromes. Annals Of Hematology 2022, 101: 557-569. PMID: 34981142, PMCID: PMC9414073, DOI: 10.1007/s00277-021-04734-2.Peer-Reviewed Original ResearchConceptsAnti-drug antibodiesAcute myeloid leukemiaDose-limiting toxicityRefractory acute myeloid leukemiaHigh-risk myelodysplastic syndromeMyelodysplastic syndromeMyeloid leukemiaCommon treatment-emergent adverse eventsTreatment-emergent adverse eventsADA-positive patientsPhase 2 dosePresence/frequencyUnexpected safety findingsPhase 1 studyAnti-CD47 antibodyCD47-SIRPα interactionMacrophage-mediated killingHematological cancer cell linesFebrile neutropeniaMonotherapy activityCancer cell linesPrimary endpointSecondary endpointsAdverse eventsObjective response
2021
Enasidenib plus azacitidine versus azacitidine alone in patients with newly diagnosed, mutant-IDH2 acute myeloid leukaemia (AG221-AML-005): a single-arm, phase 1b and randomised, phase 2 trial
DiNardo CD, Schuh AC, Stein EM, Montesinos P, Wei AH, de Botton S, Zeidan AM, Fathi AT, Kantarjian HM, Bennett JM, Frattini MG, Martin-Regueira P, Lersch F, Gong J, Hasan M, Vyas P, Döhner H. Enasidenib plus azacitidine versus azacitidine alone in patients with newly diagnosed, mutant-IDH2 acute myeloid leukaemia (AG221-AML-005): a single-arm, phase 1b and randomised, phase 2 trial. The Lancet Oncology 2021, 22: 1597-1608. PMID: 34672961, DOI: 10.1016/s1470-2045(21)00494-0.Peer-Reviewed Original ResearchMeSH KeywordsAgedAminopyridinesAntimetabolites, AntineoplasticAntineoplastic Combined Chemotherapy ProtocolsAzacitidineDrug Administration ScheduleDrug-Related Side Effects and Adverse ReactionsFemaleHumansIsocitrate DehydrogenaseLeukemia, Myeloid, AcuteMaleMutationProgression-Free SurvivalRandom AllocationTreatment OutcomeTriazinesConceptsAcute myeloid leukemiaSerious treatment-related adverse eventsTreatment-related adverse eventsDose-finding portionOverall response rateMyeloid leukemiaAdverse eventsFebrile neutropeniaCombination groupInterim analysisEastern Cooperative Oncology Group performance statusCommon treatment-related grade 3Response rateInteractive web response systemTreatment-related grade 3Phase 1b/2 trialPrespecified interim analysisTreatment-related deathsPhase 2 trialWeb response systemPhase 2Acute myeloid leukemia subtypesPhase 2 portionBristol-Myers SquibbAzacitidine monotherapyPeri‐transfusion quality‐of‐life assessment for patients with myelodysplastic syndromes
Abel GA, Klepin HD, Magnavita ES, Jaung T, Lu W, Shallis RM, Hantel A, Bahl NE, Dellinger‐Johnson R, Winer ES, Zeidan AM. Peri‐transfusion quality‐of‐life assessment for patients with myelodysplastic syndromes. Transfusion 2021, 61: 2830-2836. PMID: 34251040, DOI: 10.1111/trf.16584.Peer-Reviewed Original ResearchConceptsRed cell transfusionCell transfusionMyelodysplastic syndromeFollow-up questionnaireTransfusion decisionsQoL assessmentProportion of patientsProspective pilot studyQoL 1Repeat transfusionHemoglobin levelsPatients' qualityScore 7TransfusionPatientsStudy designQoLPilot studySignificant increaseSyndromeLife assessmentSignificant changesDaysQuestionnaireAssessment
2020
A Phase Ib Study of Onvansertib, a Novel Oral PLK1 Inhibitor, in Combination Therapy for Patients with Relapsed or Refractory Acute Myeloid Leukemia
Zeidan AM, Ridinger M, Lin TL, Becker PS, Schiller GJ, Patel PA, Spira AI, Tsai ML, Samuëlsz E, Silberman SL, Erlander M, Wang ES. A Phase Ib Study of Onvansertib, a Novel Oral PLK1 Inhibitor, in Combination Therapy for Patients with Relapsed or Refractory Acute Myeloid Leukemia. Clinical Cancer Research 2020, 26: 6132-6140. PMID: 32998961, DOI: 10.1158/1078-0432.ccr-20-2586.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAntineoplastic Combined Chemotherapy ProtocolsCytarabineDecitabineDrug Resistance, NeoplasmFemaleFollow-Up StudiesHumansLeukemia, Myeloid, AcuteMaleMaximum Tolerated DoseMiddle AgedNeoplasm Recurrence, LocalPiperazinesPrognosisPyrazolesQuinazolinesSalvage TherapyConceptsAcute myeloid leukemiaPhase Ib studyMyeloid leukemiaIb studyRefractory (R/R) AMLFirst-cycle dose-limiting toxicitiesRefractory acute myeloid leukemiaOngoing phase II trialAntileukemic activityMost grade 3Low-dose cytarabinePhase II trialBone marrow blastsDose-limiting toxicityPLK1 inhibitorsPolo-like kinase 1Evaluable patientsExploratory endpointsComplete remissionII trialPrimary endpointAdverse eventsClinical responseMarrow blastsCount recoveryMutant Isocitrate Dehydrogenase 1 Inhibitor Ivosidenib in Combination With Azacitidine for Newly Diagnosed Acute Myeloid Leukemia
DiNardo CD, Stein AS, Stein EM, Fathi AT, Frankfurt O, Schuh AC, Döhner H, Martinelli G, Patel PA, Raffoux E, Tan P, Zeidan AM, de Botton S, Kantarjian HM, Stone RM, Frattini MG, Lersch F, Gong J, Gianolio DA, Zhang V, Franovic A, Fan B, Goldwasser M, Daigle S, Choe S, Wu B, Winkler T, Vyas P. Mutant Isocitrate Dehydrogenase 1 Inhibitor Ivosidenib in Combination With Azacitidine for Newly Diagnosed Acute Myeloid Leukemia. Journal Of Clinical Oncology 2020, 39: 57-65. PMID: 33119479, PMCID: PMC7771719, DOI: 10.1200/jco.20.01632.Peer-Reviewed Original ResearchConceptsAcute myeloid leukemiaAdverse eventsQT prolongationMyeloid leukemiaMutant acute myeloid leukemiaBone marrow mononuclear cellsExpected safety profileIDH differentiation syndromeIntensive induction chemotherapyTreatment-related gradeMedian treatment durationPhase Ib trialComplete remission rateOverall response rateMarrow mononuclear cellsDifferentiation syndromeIb trialInduction chemotherapyOral ivosidenibSubcutaneous azacitidineComplete remissionComplete respondersRemission rateMedian durationOral inhibitorPhase 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 differences