2024
A review of the isocitrate dehydrogenase inhibitors in management of adult patients with AML and MDS
Norman M, Yamartino K, Gerstein R, Shallis R, Mendez L, Podoltsev N, Stahl M, Eighmy W, Zeidan A. A review of the isocitrate dehydrogenase inhibitors in management of adult patients with AML and MDS. Expert Review Of Hematology 2024, ahead-of-print: 1-13. PMID: 39474840, DOI: 10.1080/17474086.2024.2422554.Peer-Reviewed Original ResearchDiagnosed AMLSurvival benefitManagement of acute myeloid leukemiaDevelopment of oral therapiesIsocitrate dehydrogenase inhibitorsNewly diagnosed AMLManagement of adult patientsPost-transplant maintenanceAcute myeloid leukemiaSingle-arm studyExcellent response ratesIDH inhibitorsRelapsed AMLHypomethylating agentsInhibitor therapyMyelodysplastic syndromeOral therapyCombination therapyPost-transplantMyeloid leukemiaImproved survivalSingle-armAdult patientsAzacitidineRandomized studyChallenges in management of older patients with chronic myeloid leukemia
Stempel J, Shallis R, Wong R, Podoltsev N. Challenges in management of older patients with chronic myeloid leukemia. Leukemia & Lymphoma 2024, 65: 1219-1232. PMID: 38652861, DOI: 10.1080/10428194.2024.2342559.Peer-Reviewed Original ResearchChronic myeloid leukemiaTyrosine kinase inhibitorsTreatment-free remissionOlder patientsMyeloid leukemiaTyrosine kinase inhibitor dosingGeneration tyrosine kinase inhibitorsManagement of older patientsSecond-line agentsSurvival of patientsSide effect profileFront-line optionPrevalence of comorbiditiesImproved survivalCardiovascular toleranceEffect profileFavorable outcomeKinase inhibitorsPrevent progressionPatientsPersonalized treatmentQuality of lifeTreatment goalsOptimal careDiscontinuation strategiesCost-effectiveness of adding quizartinib to induction chemotherapy for patients with FLT3-mutant acute myeloid leukemia
Bewersdorf J, Patel K, Shallis R, Podoltsev N, Kewan T, Stempel J, Mendez L, Stahl M, Stein E, Huntington S, Goshua G, Zeidan A. Cost-effectiveness of adding quizartinib to induction chemotherapy for patients with FLT3-mutant acute myeloid leukemia. Leukemia & Lymphoma 2024, 65: 1136-1144. PMID: 38648559, PMCID: PMC11265977, DOI: 10.1080/10428194.2024.2344052.Peer-Reviewed Original ResearchQuality-adjusted life yearsCompletion of consolidation therapyFLT3-mutant acute myeloid leukemiaAllogeneic hematopoietic cell transplantationIncremental cost-effectiveness ratioProbabilistic sensitivity analysesImproved overall survivalHematopoietic cell transplantationPartitioned survival analysis modelAcute myeloid leukemiaCost-effectiveness ratioFLT3 inhibitor quizartinibHealth economic implicationsConsolidation therapyInduction chemotherapyAverage wholesale priceOverall survivalCell transplantationContinuous therapyMyeloid leukemiaITD mutationQuizartinibIncremental costCost-effective optionLife years
2023
A randomized phase III study of standard versus high-dose cytarabine with or without vorinostat for AML
Garcia-Manero G, Podoltsev N, Othus M, Pagel J, Radich J, Fang M, Rizzieri D, Marcucci G, Strickland S, Litzow M, Savoie M, Medeiros B, Sekeres M, Lin T, Uy G, Powell B, Kolitz J, Larson R, Stone R, Claxton D, Essell J, Luger S, Mohan S, Moseley A, Appelbaum F, Erba H. A randomized phase III study of standard versus high-dose cytarabine with or without vorinostat for AML. Leukemia 2023, 38: 58-66. PMID: 37935977, DOI: 10.1038/s41375-023-02073-x.Peer-Reviewed Original ResearchConceptsHigh-dose cytarabineAcute myeloid leukemiaDose cytarabineRandomized phase III studyUnfavorable-risk cytogeneticsRandomized multicenter trialOverall remission ratePhase III studyHigh response rateHistone deacetylase inhibitorsInduction therapyFree survivalPrimary endpointRemission rateUntreated patientsIII studyOverall survivalYounger patientsMulticenter trialImproved outcomesMyeloid leukemiaCytogenetic subsetsCytarabineResponse rateHigh dosesOlder 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 accessSupportive Care for Patients With Myelodysplastic Syndromes
Stempel J, Podoltsev N, Dosani T. Supportive Care for Patients With Myelodysplastic Syndromes. The Cancer Journal 2023, 29: 168-178. PMID: 37195773, DOI: 10.1097/ppo.0000000000000661.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsMyelodysplastic syndromeMyeloid leukemiaLow-risk diseaseTreatment-related complicationsSupportive care interventionsSupportive care measuresAcute myeloid leukemiaBone marrow disordersAntimicrobial prophylaxisFrequent complicationProgressive cytopeniasSupportive careTransfusion supportHigh-risk counterpartsBetter prognosisPalliative careRoutine immunizationCare measuresCare interventionsIneffective hematopoiesisIron overloadCommon causeMarrow disordersSyndrome populationPatientsSecond 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 myelofibrosis
2022
Cost-Effectiveness of Azacitidine and Ivosidenib in Newly Diagnosed Older, Intensive Chemotherapy-Ineligible Patients with IDH1-Mutant Acute Myeloid Leukemia
Bewersdorf J, Patel K, Goshua G, Shallis R, Podoltsev N, Stahl M, Stempel J, Stein E, Huntington S, Zeidan A. Cost-Effectiveness of Azacitidine and Ivosidenib in Newly Diagnosed Older, Intensive Chemotherapy-Ineligible Patients with IDH1-Mutant Acute Myeloid Leukemia. Blood 2022, 140: 319-321. DOI: 10.1182/blood-2022-158465.Peer-Reviewed Original ResearchA Multi-Center Phase Ib Trial of the Histone Deactylase Inhibitor (HDACi) Entinostat in Combination with Anti-PD1 Antibody Pembrolizumab in Patients with Refractory/Relapsed Myelodysplastic Syndromes (RR-MDS) or Oligoblastic Acute Myeloid Leukemia (RR-AML) after Hypomethylating Agent (HMA) Failure
Bewersdorf J, Shallis R, Sharon E, Caldwell A, Wei W, Yacoub A, Madanat Y, Zeidner J, Altman J, Odenike O, Yerrabothala S, Kovacsovics T, Podoltsev N, Halene S, Little R, Piekarz R, Gore S, Kim T, Zeidan A. A Multi-Center Phase Ib Trial of the Histone Deactylase Inhibitor (HDACi) Entinostat in Combination with Anti-PD1 Antibody Pembrolizumab in Patients with Refractory/Relapsed Myelodysplastic Syndromes (RR-MDS) or Oligoblastic Acute Myeloid Leukemia (RR-AML) after Hypomethylating Agent (HMA) Failure. Blood 2022, 140: 9084-9086. DOI: 10.1182/blood-2022-158626.Peer-Reviewed Original ResearchClinical outcomes in patients with relapsed/refractory FLT3-mutated acute myeloid leukemia treated with gilteritinib who received prior midostaurin or sorafenib
Perl AE, Hosono N, Montesinos P, Podoltsev N, Martinelli G, Panoskaltsis N, Recher C, Smith CC, Levis MJ, Strickland S, Röllig C, Groß-Langenhoff M, Chou WC, Lee JH, Yokoyama H, Hasabou N, Lu Q, Tiu RV, Altman JK. Clinical outcomes in patients with relapsed/refractory FLT3-mutated acute myeloid leukemia treated with gilteritinib who received prior midostaurin or sorafenib. Blood Cancer Journal 2022, 12: 84. PMID: 35637252, PMCID: PMC9151663, DOI: 10.1038/s41408-022-00677-7.Peer-Reviewed Original ResearchConceptsAcute myeloid leukemiaFLT3-TKIRefractory FLT3TKI exposureSalvage chemotherapyClinical outcomesMyeloid leukemiaR AMLLonger median overall survivalComposite complete remissionHigher CRCS ratesMedian overall survivalTyrosine kinase inhibitor midostaurinKinase inhibitor midostaurinPotential clinical impactADMIRAL trialCRC ratesGilteritinib armPrior sorafenibComplete remissionRemission durationOverall survivalTKI therapyTKI useSurvival outcomesCost-effectiveness of liposomal cytarabine/daunorubicin in patients with newly diagnosed acute myeloid leukemia
Bewersdorf JP, Patel KK, Goshua G, Shallis RM, Podoltsev NA, Huntington SF, Zeidan AM. Cost-effectiveness of liposomal cytarabine/daunorubicin in patients with newly diagnosed acute myeloid leukemia. Blood 2022, 139: 1766-1770. PMID: 35298594, PMCID: PMC8931513, DOI: 10.1182/blood.2021014401.Peer-Reviewed Original Research
2021
Hypomethylating Agents and FLT3 Inhibitors As Maintenance Treatment for Acute Myeloid Leukemia and Myelodysplastic Syndrome After Allogeneic Hematopoietic Stem Cell Transplantation–A Systematic Review and Meta-Analysis
Bewersdorf JP, Allen C, Mirza AS, Grimshaw AA, Giri S, Podoltsev NA, Gowda L, Cho C, Tallman MS, Zeidan AM, Stahl M. Hypomethylating Agents and FLT3 Inhibitors As Maintenance Treatment for Acute Myeloid Leukemia and Myelodysplastic Syndrome After Allogeneic Hematopoietic Stem Cell Transplantation–A Systematic Review and Meta-Analysis. Transplantation And Cellular Therapy 2021, 27: 997.e1-997.e11. PMID: 34551341, PMCID: PMC9533376, DOI: 10.1016/j.jtct.2021.09.005.Peer-Reviewed Original ResearchConceptsAcute myeloid leukemiaRelapse-free survivalMaintenance therapyMyelodysplastic syndromeFLT3 inhibitorsAllo-HCTHazard ratioMaintenance treatmentClinical trialsMyeloid leukemiaAllogeneic hematopoietic stem cell transplantationControl groupSystematic reviewAllogeneic hematopoietic cell transplantMeasurable residual disease statusHematopoietic stem cell transplantationMeasurable residual disease testingNon-relapse mortalityHematopoietic cell transplantPre-emptive treatmentResidual disease statusStem cell transplantationFavorable safety profileSame patient cohortRandom-effects modelVenetoclax-based combinations in AML and high-risk MDS prior to and following allogeneic hematopoietic cell transplant
Bewersdorf JP, Derkach A, Gowda L, Menghrajani K, DeWolf S, Ruiz JD, Ponce DM, Shaffer BC, Tamari R, Young JW, Jakubowski AA, Gyurkocza B, Chan A, Xiao W, Glass J, King AC, Cai SF, Daniyan A, Famulare C, Cuello BM, Podoltsev NA, Roshal M, Giralt S, Perales MA, Seropian S, Cho C, Zeidan AM, Prebet T, Stein EM, Tallman MS, Goldberg AD, Stahl M. Venetoclax-based combinations in AML and high-risk MDS prior to and following allogeneic hematopoietic cell transplant. Leukemia & Lymphoma 2021, 62: 3394-3401. PMID: 34477024, PMCID: PMC9012492, DOI: 10.1080/10428194.2021.1966788.Peer-Reviewed Original ResearchConceptsAcute myeloid leukemiaAllogeneic hematopoietic cell transplantAllo-HCTHematopoietic cell transplantSalvage therapyMyelodysplastic syndromeCell transplantMemorial Sloan-Kettering Cancer CenterHigh-risk myelodysplastic syndromeSecond allo-HCTSalvage treatment optionOverall response rateMedian followMedian OSVenetoclax therapyRetrospective studyCancer CenterTreatment optionsOS estimatesMyeloid leukemiaPatientsResponse rateTherapyTransplantMonthsLaboratory evaluation and prognostication among adults and children with CEBPA‐mutant acute myeloid leukemia
Mendoza H, Podoltsev NA, Siddon AJ. Laboratory evaluation and prognostication among adults and children with CEBPA‐mutant acute myeloid leukemia. International Journal Of Laboratory Hematology 2021, 43: 86-95. PMID: 34288448, DOI: 10.1111/ijlh.13517.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsCEBPA mutant acute myeloid leukemiaAcute myeloid leukemiaCEBPA mutationsMyeloid leukemiaLeukemogenic mutationsPositive prognostic impactSingle CEBPA mutationsSimilar survival outcomesNegative prognostic effectFLT3-ITD mutationLaboratory evaluationWild-type CEBPAMultiparameter flow cytometryGermline CEBPA mutationsFavorable prognosisPrognostic impactMutation presencePrognostic effectRisk stratificationSurvival outcomesGATA2 mutationsDistinct subtypesMolecular findingsCEBPA geneFlow cytometryA Phase I dose‐escalation study of DCLL9718S, an antibody‐drug conjugate targeting C‐type lectin‐like molecule‐1 (CLL‐1) in patients with acute myeloid leukemia
Daver N, Salhotra A, Brandwein JM, Podoltsev NA, Pollyea DA, Jurcic JG, Assouline S, Yee K, Li M, Pourmohamad T, Samineni D, Sumiyoshi T, Vaze A, Dere RC, Ma C, Cooper J. A Phase I dose‐escalation study of DCLL9718S, an antibody‐drug conjugate targeting C‐type lectin‐like molecule‐1 (CLL‐1) in patients with acute myeloid leukemia. American Journal Of Hematology 2021, 96: e175-e179. PMID: 33617672, PMCID: PMC8252033, DOI: 10.1002/ajh.26136.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAntibodiesAntineoplastic AgentsChemical and Drug Induced Liver InjuryDose-Response Relationship, DrugEarly Termination of Clinical TrialsFemaleHumansImmunoconjugatesLectins, C-TypeLeukemia, Myeloid, AcuteMaleMiddle AgedMutationNeoplasm ProteinsNeoplasms, Second PrimaryReceptors, MitogenYoung AdultCost-effectiveness of azacitidine and venetoclax in unfit patients with previously untreated acute myeloid leukemia
Patel KK, Zeidan AM, Shallis RM, Prebet T, Podoltsev N, Huntington SF. Cost-effectiveness of azacitidine and venetoclax in unfit patients with previously untreated acute myeloid leukemia. Blood Advances 2021, 5: 994-1002. PMID: 33591323, PMCID: PMC7903235, DOI: 10.1182/bloodadvances.2020003902.Peer-Reviewed Original ResearchConceptsUntreated acute myeloid leukemiaIncremental cost-effectiveness ratioAcute myeloid leukemiaUnfit patientsMyeloid leukemiaLifetime health care costsSignificant price reductionUntreated AML patientsOverall survival curvesUS payer perspectiveCost-effectiveness ratioParametric survival modelingHealth care costsPrice reductionIntensive chemotherapyOverall survivalAML patientsTreatment strategiesCurrent pricingResponse rateCare costsSurvival curvesVenetoclaxClinical settingAzacitidineContemporary practice patterns of tyrosine kinase inhibitor use among older patients with chronic myeloid leukemia in the United States
Shallis RM, Wang R, Bewersdorf JP, Zeidan AM, Davidoff AJ, Huntington SF, Podoltsev NA, Ma X. Contemporary practice patterns of tyrosine kinase inhibitor use among older patients with chronic myeloid leukemia in the United States. Therapeutic Advances In Hematology 2021, 12: 20406207211043404. PMID: 35154624, PMCID: PMC8832334, DOI: 10.1177/20406207211043404.Peer-Reviewed Original ResearchChronic phase chronic myeloid leukemiaFrontline tyrosine kinase inhibitorsTyrosine kinase inhibitorsOlder patientsChronic myeloid leukemiaTKI switchingMyeloid leukemiaSecond-generation tyrosine kinase inhibitorsBCR-ABL1 tyrosine kinase inhibitorsTyrosine kinase inhibitor useOlder CML patientsEnd Results-MedicareFavorable safety profileSpecific patient populationsContemporary practice patternsFrontline imatinibTKI choiceGreater comorbidityMost patientsInhibitor usePatient characteristicsWhite patientsDiagnosis yearTKI useCML patients
2020
Maintenance therapy for acute myeloid leukemia: sustaining the pursuit for sustained remission.
Shallis RM, Podoltsev NA. Maintenance therapy for acute myeloid leukemia: sustaining the pursuit for sustained remission. Current Opinion In Hematology 2020, 28: 110-121. PMID: 33394722, DOI: 10.1097/moh.0000000000000637.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsMeSH KeywordsAntineoplastic AgentsAntineoplastic Combined Chemotherapy ProtocolsBiomarkers, TumorClinical Decision-MakingCombined Modality TherapyDisease ManagementDisease SusceptibilityHematopoietic Stem Cell TransplantationHumansLeukemia, Myeloid, AcuteMaintenance ChemotherapyRandomized Controlled Trials as TopicRemission InductionTreatment OutcomeConceptsAcute myeloid leukemiaMaintenance therapyMeasurable residual diseaseMyeloid leukemiaOral hypomethylating agentPost-transplant settingImmune checkpoint inhibitorsPlacebo-controlled trialHigh-risk diseaseAML patient populationRecent positive findingsMRD statusSustained remissionCheckpoint inhibitorsAML patientsRandomized trialsResidual diseasePatient populationHypomethylating agentMRD techniquesTherapyPositive findingsPatientsBcl-2RemissionHigh dose cyclophosphamide for cytoreduction in patients with acute myeloid leukemia with hyperleukocytosis or leukostasis
Zhao J, Bewersdorf JP, Jaszczur S, Kowalski A, Perreault S, Schiffer M, Gore S, Podoltsev N, Prebet T, Shallis R, Zeidan AM. High dose cyclophosphamide for cytoreduction in patients with acute myeloid leukemia with hyperleukocytosis or leukostasis. Leukemia & Lymphoma 2020, 62: 1195-1202. PMID: 33325761, DOI: 10.1080/10428194.2020.1856835.Peer-Reviewed Original ResearchConceptsWhite blood cell countHigh-dose cyclophosphamideAcute myeloid leukemiaMyeloid leukemiaDose cyclophosphamideBlast phase chronic myeloid leukemiaMedian white blood cell countPhase chronic myeloid leukemiaAdverse effectsSymptoms of leukostasisTumor lysis syndromeDay of admissionBlood cell countChronic myeloid leukemiaEvaluable patientsLeukostasis symptomsIntensive chemotherapyIntravascular coagulopathyLysis syndromePrimary endpointHemorrhagic cystitisEarly mortalityMedical emergencyCell countPatientsMyeloid sarcoma, chloroma, or extramedullary acute myeloid leukemia tumor: A tale of misnomers, controversy and the unresolved
Shallis RM, Gale RP, Lazarus HM, Roberts KB, Xu ML, Seropian SE, Gore SD, Podoltsev NA. Myeloid sarcoma, chloroma, or extramedullary acute myeloid leukemia tumor: A tale of misnomers, controversy and the unresolved. Blood Reviews 2020, 47: 100773. PMID: 33213985, DOI: 10.1016/j.blre.2020.100773.Peer-Reviewed Original ResearchConceptsAcute myeloid leukemiaMyeloid sarcomaAllogeneic hematopoietic cell transplantWorld Health Organization classificationAcute myeloid leukemia tumorsLeukemia tumorsOutcomes of patientsPost-remission therapyHematopoietic cell transplantMedian latency periodIndependent prognostic impactBone marrow evaluationAnti-leukemia therapyPET/CTCellular adhesion moleculesPatient characteristicsPrognostic impactLocal therapyCell transplantMarrow evaluationOrganization classificationConventional chemotherapyMyeloid leukemiaTherapeutic approachesReceptor/ligand