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 studyIntensive induction chemotherapy vs hypomethylating agents in combination with venetoclax in NPM1-mutant AML
Bewersdorf J, Shimony S, Shallis R, Liu Y, Berton G, Schaefer E, Zeidan A, Goldberg A, Stein E, Marcucci G, Bystrom R, Lindsley R, Chen E, Perez J, Stein A, Pullarkat V, Aldoss I, DeAngelo D, Neuberg D, Stone R, Garciaz S, Ball B, Stahl M. Intensive induction chemotherapy vs hypomethylating agents in combination with venetoclax in NPM1-mutant AML. Blood Advances 2024, 8: 4845-4855. PMID: 38941537, PMCID: PMC11416634, DOI: 10.1182/bloodadvances.2024012858.Peer-Reviewed Original ResearchIntensive induction chemotherapyAcute myeloid leukemiaNPM1-Mutant Acute Myeloid LeukemiaInduction chemotherapyHypomethylating agentsMulticenter retrospective cohort study of patientsPatients treated with ICAllogeneic stem cell transplantationRetrospective cohort study of patientsMulticenter retrospective cohort studyCohort study of patientsComposite complete remissionStem cell transplantationYears-oldFLT3-ITD mutationStudy of patientsStandard of careNormal cytogeneticsComplete remissionCell transplantationNPM1 mutationsMyeloid leukemiaFLT3-ITDYounger patientsOlder patientsBeyond HMAs: Novel targets and therapeutic approaches
Getz T, Bewersdorf J, Kewan T, Stempel J, Bidikian A, Shallis R, Stahl M, Zeidan A. Beyond HMAs: Novel targets and therapeutic approaches. Seminars In Hematology 2024 PMID: 39389839, DOI: 10.1053/j.seminhematol.2024.08.001.Peer-Reviewed Original ResearchAcute myeloid leukemiaDelays progression to acute myeloid leukemiaHeterogeneous group of clonal hematopoietic disordersGroup of clonal hematopoietic disordersMolecular International Prognostic Scoring SystemRandomized phase 3 clinical trialProgression to acute myeloid leukemiaInternational Prognostic Scoring SystemLower-risk MDS patientsRisk stratification of patientsPhase 3 clinical trialsCombination of azacitidineHypomethylating agent combinationsCurrent treatment landscapeFirst line therapyPrognostic Scoring SystemBiomarker-directed therapiesClonal hematopoietic disordersLack of therapeutic agentsStratification of patientsEarly phase trialsErythropoiesis stimulating agentsTreated with therapiesVariable clinical featuresStandard of careReal‐world outcomes of intensive induction approaches in core binding factor acute myeloid leukemia
Rojek A, McCormick B, Cwykiel J, Odetola O, Abaza Y, Nai N, Foucar C, Achar R, Shallis R, Bradshaw D, Standridge M, Kota V, Murthy S, Badar T, Patel A. Real‐world outcomes of intensive induction approaches in core binding factor acute myeloid leukemia. EJHaem 2024, 5: 728-737. PMID: 39157611, PMCID: PMC11327707, DOI: 10.1002/jha2.981.Peer-Reviewed Original ResearchPatients treated with ICEvent-free survivalTreated with ICCore binding factor acute myeloid leukemiaGemtuzumab ozogamicinIntensive chemotherapyCBF-AMLAcute myeloid leukemiaKIT inhibitorsOverall survivalEuropean LeukemiaNetMyeloid leukemiaThree-year overall survivalMedian follow-upInduction treatment regimensAntibody-drug conjugatesStatistically significant differenceImproved OSFavorable riskSurvival benefitTreatment regimensProspective studyFollow-upCompare outcomesAcademic centersTreatment approach and outcomes of patients with accelerated/blast-phase myeloproliferative neoplasms in the current era
Patel A, Yoon J, Johnston H, Davidson M, Shallis R, Chen E, Burkart M, Oh T, Iyer S, Madarang E, Muthiah C, Gross I, Dean R, Kassner J, Viswabandya A, Madero-Marroquin R, Rampal R, Murthy S, Bradley T, Abaza Y, Garcia J, Gupta V, Pettit K, Cursio J, Odenike O. Treatment approach and outcomes of patients with accelerated/blast-phase myeloproliferative neoplasms in the current era. Blood Advances 2024, 8: 3468-3477. PMID: 38739724, PMCID: PMC11260843, DOI: 10.1182/bloodadvances.2024012880.Peer-Reviewed Original ResearchAcute myeloid leukemiaOutcomes of patientsMyeloproliferative neoplasmsMPN-AP/BPAllo-HCTMedian OSIntensive chemotherapyOverall survivalEuropean LeukemiaNetSurvival outcomesAllogeneic hematopoietic stem cell transplantationAssociated with poor survival outcomesHematopoietic stem cell transplantationInvestigate outcomes of patientsProgression of myeloproliferative neoplasmsMedian overall survivalStem cell transplantationFirst-line treatmentPoor survival outcomesMulti-center analysisAssociation of responseBlast-phaseMPN-BPCell transplantationAnalyzed patientsPrognostic impact of 'multi-hit' <i>versus</i> 'single-hit' <i>TP53</i> alteration in patients with acute myeloid leukemia: results from the Consortium on Myeloid Malignancies and Neoplastic Diseases.
Badar T, Nanaa A, Atallah E, Shallis R, Craver E, Li Z, Goldberg A, Saliba A, Patel A, Bewersdorf J, Duvall A, Burkart M, Bradshaw D, Abaza Y, Stahl M, Palmisiano N, Murthy G, Zeidan A, Kota V, Patnaik M, Litzow M. Prognostic impact of 'multi-hit' versus 'single-hit' TP53 alteration in patients with acute myeloid leukemia: results from the Consortium on Myeloid Malignancies and Neoplastic Diseases. Haematologica 2024, 109: 3533-3542. PMID: 38813716, PMCID: PMC11532685, DOI: 10.3324/haematol.2024.285000.Peer-Reviewed Original ResearchAcute myeloid leukemiaMyelodysplastic syndromeComplex cytogeneticsMyeloid leukemiaAllogeneic hematopoietic stem cell transplantationLower-risk myelodysplastic syndromesHematopoietic stem cell transplantationHigher-risk myelodysplastic syndromesOutcomes of SHStem cell transplantationAllo-HCTTP53 alterationsPrognostic impactMyeloid malignanciesTP53 mutationsCell transplantationFLT3-ITDIDH1 mutationMultivariate analysisSupportive careUS academic institutionsNeoplastic diseasePatientsSuperior EFSPredicting outcomeCost-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 yearsHypomethylating 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 treatmentComparing venetoclax in combination with hypomethylating agents to hypomethylating agent-based therapies for treatment naive TP53-mutated acute myeloid leukemia: results from the Consortium on Myeloid Malignancies and Neoplastic Diseases (COMMAND)
Badar T, Nanaa A, Atallah E, Shallis R, Guilherme S, Goldberg A, Saliba A, Patel A, Bewersdorf J, DuVall A, Bradshaw D, Abaza Y, Murthy G, Palmisiano N, Zeidan A, Kota V, Litzow M. Comparing venetoclax in combination with hypomethylating agents to hypomethylating agent-based therapies for treatment naive TP53-mutated acute myeloid leukemia: results from the Consortium on Myeloid Malignancies and Neoplastic Diseases (COMMAND). Blood Cancer Journal 2024, 14: 32. PMID: 38378617, PMCID: PMC10879201, DOI: 10.1038/s41408-024-01000-2.Peer-Reviewed Original ResearchClinical outcomes of hypomethylating agents plus Venetoclax as frontline treatment in patients 75 years and older with acute myeloid leukemia: Real‐world data from eight US academic centers
Abaza Y, Winer E, Murthy S, Shallis R, Matthews A, Badar T, Geramita E, Kota V, Swaroop A, Doukas P, Bradshaw D, Helenowski I, Liu Y, Zhang H, Im A, Litzow M, Perl A, Atallah E, Altman J. Clinical outcomes of hypomethylating agents plus Venetoclax as frontline treatment in patients 75 years and older with acute myeloid leukemia: Real‐world data from eight US academic centers. American Journal Of Hematology 2024, 99: 606-614. PMID: 38342997, DOI: 10.1002/ajh.27231.Peer-Reviewed Original ResearchAcute myeloid leukemiaHypomethylating agentsOverall survivalElderly patientsMedian OSMyeloid leukemiaTP53-mutated acute myeloid leukemiaNewly diagnosed acute myeloid leukemiaFailure of hypomethylating agentsMedian duration of responseDiagnosed AMLVIALE-A trialMedian overall survivalIncomplete count recoveryDuration of responseMulticenter retrospective studySingle-center studyTreatment of patientsStandard of careCR/CRi rateIntensive chemotherapyCount recoveryMedian durationFrontline treatmentRetrospective studyIntegrated genetic, epigenetic, and immune landscape of TP53 mutant AML and higher risk MDS treated with azacitidine
Zeidan A, Bewersdorf J, Hasle V, Shallis R, Thompson E, de Menezes D, Rose S, Boss I, Halene S, Haferlach T, Fox B. Integrated genetic, epigenetic, and immune landscape of TP53 mutant AML and higher risk MDS treated with azacitidine. Therapeutic Advances In Hematology 2024, 15: 20406207241257904. PMID: 38883163, PMCID: PMC11180421, DOI: 10.1177/20406207241257904.Peer-Reviewed Original ResearchHigher-risk myelodysplastic syndromesAcute myeloid leukemiaBone marrowMutation statusImmune landscapeImmunological landscapeAnti-PD-L1 antibody durvalumabHR-MDS patientsWild-type acute myeloid leukemiaTP53-mutant acute myeloid leukemiaMutant acute myeloid leukemiaAzacitidine-based therapyWild-type patientsImmune checkpoint proteinsImmune checkpoint expressionT cell populationsWild-typeStatistically significant decreaseAZA therapyImmunosuppressive microenvironmentPD-L1Mutant patientsDNA methylation arraysCheckpoint expressionMyelodysplastic syndrome
2023
Intensive Induction Chemotherapy (IC) Vs Hypomethylating Agents + Venetoclax (HMA/VEN) in IDH1- or IDH2-Mutant Newly Diagnosed Acute Myeloid Leukemia (AML) - a Multicenter Cohort Study
Bewersdorf J, Shimony S, Shallis R, Liu Y, Schaefer E, Zeidan A, Goldberg A, Stein E, Marcucci G, Lindsley R, Chen E, Ramos J, Stein A, DeAngelo D, Neuberg D, Stone R, Ball B, Stahl M. Intensive Induction Chemotherapy (IC) Vs Hypomethylating Agents + Venetoclax (HMA/VEN) in IDH1- or IDH2-Mutant Newly Diagnosed Acute Myeloid Leukemia (AML) - a Multicenter Cohort Study. Blood 2023, 142: 1589. DOI: 10.1182/blood-2023-174283.Peer-Reviewed Original ResearchIntensive induction chemotherapyAcute myeloid leukemiaComposite complete responseMedian overall survivalOverall survivalComplete responseIDH2 mutationsAllo-SCTLarge multicenter retrospective cohort studyMulticenter retrospective cohort studyAllogeneic stem cell transplantationSecondary acute myeloid leukemiaComparable overall survivalIDH1 inhibitor ivosidenibHigh rateRetrospective cohort studyStem cell transplantationLog-rank testStandard of careLarge academic centerYears of ageEffect of treatmentIDH-mutant AMLMultivariable stepwiseFit patientsWhat Is the Optimal Treatment Modality in Molecularly Defined Secondary AML? a Multicenter Cohort Study
Shimony S, Bewersdorf J, Shallis R, Liu Y, Schaefer E, Zeidan A, Goldberg A, Stein E, Marcucci G, Chen E, Ramos J, Lindsley R, Stein A, DeAngelo D, Neuberg D, Stone R, Ball B, Stahl M. What Is the Optimal Treatment Modality in Molecularly Defined Secondary AML? a Multicenter Cohort Study. Blood 2023, 142: 1478. DOI: 10.1182/blood-2023-172763.Peer-Reviewed Original ResearchAcute myeloid leukemiaComposite complete responseStem cell transplantationOverall survivalCPX-351Complete responseTreatment modalitiesMonosomal karyotypeCohort studyOdds ratioTreatment groupsLarge multicenter retrospective cohort studyMulticenter retrospective cohort studyAllogeneic stem cell transplantationSecondary acute myeloid leukemiaIncomplete count recoveryImproved overall survivalMedian overall survivalMulticenter cohort studyRetrospective cohort studyWorse overall survivalOptimal treatment modalityOptimal treatment selectionLog-rank testEffect of treatmentIntensive Induction Chemotherapy Vs Hypomethylating Agents + Venetoclax (HMA/VEN) in NPM1-Mutant Newly Diagnosed Acute Myeloid Leukemia (AML) - a Multicenter Cohort Study
Bewersdorf J, Shimony S, Shallis R, Liu Y, Schaefer E, Zeidan A, Goldberg A, Stein E, Marcucci G, Lindsley R, Chen E, Ramos J, Stein A, DeAngelo D, Neuberg D, Stone R, Ball B, Stahl M. Intensive Induction Chemotherapy Vs Hypomethylating Agents + Venetoclax (HMA/VEN) in NPM1-Mutant Newly Diagnosed Acute Myeloid Leukemia (AML) - a Multicenter Cohort Study. Blood 2023, 142: 2964. DOI: 10.1182/blood-2023-174285.Peer-Reviewed Original ResearchNPM1 mutant acute myeloid leukemiaIntensive induction chemotherapyAcute myeloid leukemiaComposite complete responseMedian overall survivalOverall survivalComplete responseAllo-SCTPt ageAbnormal cytogeneticsCohort studyMyelodysplastic syndromePolymerase chain reactionClinical trialsMyeloid leukemiaNPM1 mutationsLarge multicenter retrospective cohort studyTime-varying covariatesMulticenter retrospective cohort studyAllogeneic stem cell transplantationPrior myelodysplastic syndromeMulticenter cohort studyRetrospective cohort studyStem cell transplantationPrior chemotherapy exposureOutcomes of Patients Receiving Intensive Therapy for Acute Myeloid Leukemia Relapsed after/Refractory to Frontline Less-Intensive Therapy
Achar R, McCormick B, Dworkin E, Geramita E, Im A, Patel A, Badar T, Shallis R. Outcomes of Patients Receiving Intensive Therapy for Acute Myeloid Leukemia Relapsed after/Refractory to Frontline Less-Intensive Therapy. Blood 2023, 142: 5859. DOI: 10.1182/blood-2023-179336.Peer-Reviewed Original ResearchOverall response rateAcute myeloid leukemiaMedian overall survivalMajority of ptsIntensive induction therapyIntensive therapyOverall survivalComplete remissionFrontline therapyR therapyInduction chemotherapyInduction therapyCPX-351Eastern Cooperative Oncology Group performance statusExact testResponse rateMorphologic leukemia-free stateR AMLRelapsed/refractory (R/R) diseaseHematopoietic stem cell transplantationCox proportional hazards modelContinuous variablesAdverse-risk diseaseIncomplete count recoveryIntensive induction chemotherapyIntensive Induction Chemotherapy with or without Gemtuzumab Ozogamicin Among Patients with Core-Binding Factor Acute Myeloid Leukemia
Rojek A, McCormick B, Cwykiel J, Odetola O, Abaza Y, Achar R, Shallis R, Bradshaw D, Standridge M, Kota V, Badar T, Patel A. Intensive Induction Chemotherapy with or without Gemtuzumab Ozogamicin Among Patients with Core-Binding Factor Acute Myeloid Leukemia. Blood 2023, 142: 2889. DOI: 10.1182/blood-2023-177758.Peer-Reviewed Original ResearchRelapse-free survivalAddition of GOFactor acute myeloid leukemiaGemtuzumab ozogamicinIntensive chemotherapyIntensive induction chemotherapyOverall survivalAcute myeloid leukemiaCBF-AMLComplete responseKIT inhibitorsInduction chemotherapyRemission rateProspective studyPolymerase chain reactionMyeloid leukemiaCore binding factor acute myeloid leukemiaAllogeneic stem cell transplantationMulti-center retrospective studyCore-binding factor acute myeloid leukemiaMeasurable residual disease testingAnthracycline-based inductionEuropean LeukemiaNet guidelinesFavorable-risk AMLInduction-related mortalityComparable Survival of Treatment Naïve TP53 Mutated Acute Myeloid Leukemia Treated with Hypomethylating Agent Compared to Hypomethylating Agent Plus Venetoclax Based Therapy
Badar T, Atallah E, Shallis R, Patel A, De Camargo Correia G, Goldberg A, Saliba A, Bewersdorf J, Duvall A, Bradshaw D, Abaza Y, Murthy S, Palmisiano N, Kota V, Litzow M. Comparable Survival of Treatment Naïve TP53 Mutated Acute Myeloid Leukemia Treated with Hypomethylating Agent Compared to Hypomethylating Agent Plus Venetoclax Based Therapy. Blood 2023, 142: 592. DOI: 10.1182/blood-2023-184626.Peer-Reviewed Original ResearchAcute myeloid leukemiaComplete remission rateOverall survivalDuration of responseMultivariable analysisComplex cytogeneticsAllo-HCTRemission rateMyeloid leukemiaAllogeneic stem cell transplantSecondary acute myeloid leukemiaAdverse-risk diseaseCR/CRiMedian overall survivalOutcome of ptsResults Baseline characteristicsKaplan-Meier methodMore effective treatment strategiesSignificant univariate predictorsStem cell transplantEffective treatment strategiesReal-world studyLogistic regression modelsMedian followVEN groupTreatment Patterns Among Patients with Relapsed/Refractory Core-Binding Factor Acute Myeloid Leukemia after Intensive Induction Chemotherapy
Rojek A, McCormick B, Cwykiel J, Odetola O, Abaza Y, Achar R, Shallis R, Bradshaw D, Standridge M, Kota V, Badar T, Patel A. Treatment Patterns Among Patients with Relapsed/Refractory Core-Binding Factor Acute Myeloid Leukemia after Intensive Induction Chemotherapy. Blood 2023, 142: 1484. DOI: 10.1182/blood-2023-185163.Peer-Reviewed Original ResearchCore-binding factor acute myeloid leukemiaFactor acute myeloid leukemiaIntensive induction chemotherapyOutcome of ptsInitial complete remissionLine therapyComplete remissionLong-term outcomesAcute myeloid leukemiaCBF-AMLPolymerase chain reactionR diseaseInduction chemotherapyMedian OSFirst relapseIntensive inductionInitial diagnosisMyeloid leukemiaMolecular testingNext-generation sequencingKIT inhibitorsMulti-center retrospective studyMeasurable residual disease testingAnthracycline-based inductionEuropean LeukemiaNet guidelinesSecond 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
Venetoclax-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