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, 17: 755-767. 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 studyImpact of Molecular Ontogeny on Hematological Recovery in AML Patients Treated with Hypomethylating Agent Plus Venetoclax Therapy
Zhang J, Shimony S, Liu Y, Inyang E, Chen E, Aguirre L, Bystrom R, Rolles B, Stone R, DeAngelo D, Tiao E, Stahl M. Impact of Molecular Ontogeny on Hematological Recovery in AML Patients Treated with Hypomethylating Agent Plus Venetoclax Therapy. Blood 2024, 144: 5175-5175. DOI: 10.1182/blood-2024-200358.Peer-Reviewed Original ResearchAcute myeloid leukemiaAbsolute neutrophil countTP53-mutated acute myeloid leukemiaDe novo acute myeloid leukemiaMorphologic leukemia-free stateTP53-MTDe novo groupHypomethylating agentsCount recoveryTP53 mutationsRed blood cellsNewly diagnosed acute myeloid leukemiaMedian absolute neutrophil countHigh-risk myelodysplastic syndromePresence of TP53 mutationsDiagnosed AMLCycle 3Acute myeloid leukemia patientsCycle 1Dose of venetoclaxAssociated with prior historyCycle lengthIncomplete count recoveryBlood cellsCycles of treatmentHMA/Ven Treatment Modifications and Associated Outcomes in IDH -Mutant AML
Chin K, Derkach A, Famulare C, Gupta G, Borge P, Geyer M, Goldberg A, Haque T, Park J, Roeker L, Tallman M, Stahl M, Stein E. HMA/Ven Treatment Modifications and Associated Outcomes in IDH -Mutant AML. Blood 2024, 144: 5962-5962. DOI: 10.1182/blood-2024-211733.Peer-Reviewed Original ResearchAcute myeloid leukemiaMedian overall survivalIsocitrate dehydrogenase-mutantCommon Terminology Criteria for Adverse EventsMeasurable residual diseaseOverall survivalTreatment modificationNo significant differenceCR/CRi rateMRD negativityHypomethylating agentsSignificant differenceLong-term survival outcomesSingle-center retrospective studyToxicity associated with treatmentMutant acute myeloid leukemiaCycle lengthChemotherapy-ineligible patientsGrade 3 neutropeniaMRD-negativity ratesTreatment cycle characteristicsAssociated with higher responseEvent-free survivalKaplan-Meier methodologyEfficacious treatment regimensTargeted therapies for myelodysplastic syndromes/neoplasms (MDS): current landscape and future directions
Bidikian A, Bewersdorf J, Shallis R, Getz T, Stempel J, Kewan T, Stahl M, Zeidan A. Targeted therapies for myelodysplastic syndromes/neoplasms (MDS): current landscape and future directions. Expert Review Of Anticancer Therapy 2024, 24: 1131-1146. PMID: 39367718, DOI: 10.1080/14737140.2024.2414071.Peer-Reviewed Original ResearchErythropoiesis-stimulating agentsTargeted therapyLR-MDSHR-MDSHypoxia-inducible factorAllogeneic hematopoietic stem cell transplantationLandscape of targeted therapiesHematopoietic stem cell transplantationHeterogeneous group of hematologic malignanciesGroup of hematologic malignanciesMolecular prognostic toolsDuration of responseStem cell transplantationTrial designClinical trial designHypomethylating agentsCell transplantationHematologic malignanciesImprove patient outcomesRNA splicing machineryImmune evasionPrognostic toolTGF-betaTherapyEffective treatmentHMA/VEN treatment modifications and associated outcomes in IDH-mutant AML
Chin K, Derkach A, Famulare C, Gupta G, Borge P, Geyer M, Goldberg A, Haque T, Park J, Roeker L, Tallman M, Stahl M, Stein E. HMA/VEN treatment modifications and associated outcomes in IDH-mutant AML. Leukemia & Lymphoma 2024, 66: 270-278. PMID: 39397429, DOI: 10.1080/10428194.2024.2411436.Peer-Reviewed Original ResearchConceptsAcute myeloid leukemiaTreatment modificationHypomethylating agentsResponse rateAssociated with lower response ratesMedian overall survivalIDH-mutated acute myeloid leukemiaLong-term toxicityCR/CRi rateSignificant neutropeniaFebrile neutropeniaInduction chemotherapyOverall survivalMyeloid leukemiaLow response rateSurvival rateAffect survivalNeutropeniaVenetoclaxSurvivalED visitsPatientsR/RMonthsReal-world settingsIntensive 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 patientsAcute 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 implicationsCombination therapy with hypomethylating agents and venetoclax versus intensive induction chemotherapy in IDH1‐ or IDH2‐mutant newly diagnosed acute myeloid leukemia—A multicenter cohort study
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, Ramos J, Stein A, Pullarkat V, Aldoss I, DeAngelo D, Neuberg D, Stone R, Garciaz S, Ball B, Stahl M. Combination therapy with hypomethylating agents and venetoclax versus intensive induction chemotherapy in IDH1‐ or IDH2‐mutant newly diagnosed acute myeloid leukemia—A multicenter cohort study. American Journal Of Hematology 2024, 99: 1640-1643. PMID: 38751104, DOI: 10.1002/ajh.27366.Peer-Reviewed Original ResearchMolecular ontogeny underlies the benefit of adding venetoclax to hypomethylating agents in newly diagnosed AML patients
Shimony S, Garcia J, Keating J, Chen E, Luskin M, Stahl M, Neuberg D, DeAngelo D, Stone R, Lindsley R. Molecular ontogeny underlies the benefit of adding venetoclax to hypomethylating agents in newly diagnosed AML patients. Leukemia 2024, 38: 1494-1500. PMID: 38538860, PMCID: PMC11216982, DOI: 10.1038/s41375-024-02230-w.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAdultAgedAged, 80 and overAntineoplastic Combined Chemotherapy ProtocolsBridged Bicyclo Compounds, HeterocyclicDNA MethylationFemaleHematopoietic Stem Cell TransplantationHumansLeukemia, Myeloid, AcuteMaleMiddle AgedMutationPrognosisRemission InductionSulfonamidesSurvival RateTumor Suppressor Protein p53Young AdultConceptsAcute myeloid leukemiaDiagnosed AML patientsHypomethylating agentsAML patientsTP53-mutated acute myeloid leukemiaPatients treated with intensive chemotherapyAllogeneic hematopoietic stem cell transplantationHematopoietic stem cell transplantationComposite complete remissionStem cell transplantationGroup of patientsMolecular ontogenyMedian OSOS benefitComplete remissionIntensive chemotherapyCell transplantationClinicopathological variablesMyeloid leukemiaClinical benefitClinical impactSplicing mutationPatientsSecondary groupVenetoclaxHypomethylating 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
Phase 1 Study of BXCL701, a Dipeptidyl Peptidase Inhibitor, in Relapsed/Refractory Acute Myeloid Leukemia and High-Risk Myelodysplastic Syndrome
Winer E, Garcia J, Stone R, Wadleigh M, Luskin M, Stahl M, Chen E, Leonard R, Noyes A, Galinsky I, Deshpande R, Borderies P, O'Neill V, DeAngelo D. Phase 1 Study of BXCL701, a Dipeptidyl Peptidase Inhibitor, in Relapsed/Refractory Acute Myeloid Leukemia and High-Risk Myelodysplastic Syndrome. Blood 2023, 142: 1549. DOI: 10.1182/blood-2023-186598.Peer-Reviewed Original ResearchRelapsed/refractory AMLHypomethylating agentsMetastatic castration-resistant prostate cancerCycles of HMARecommended phase 2 doseRelapsed/refractory acute myeloid leukemiaAllogeneic bone marrow transplantationCastration-resistant prostate cancerHigh-risk myelodysplastic syndromeNon-small cell lung cancerOral small-molecule inhibitorPhase 2 doseNon-Hodgkin's lymphomaDuration of responseMaximum tolerated doseECOG performance statusT cell responsesAdequate renal functionBone marrow transplantationAdequate liver functionPhase 1 studyCell lung cancerInduction of IL-18Acute myeloid leukemiaActivation of inflammatory cytokinesMolecular Ontogeny in AML Is Both Prognostic and Predictive in Patients Treated with Hypomethylating Agents Plus Venetoclax
Shimony S, Garcia J, Keating J, Chen E, Luskin M, Stahl M, Neuberg D, DeAngelo D, Stone R, Lindsley R. Molecular Ontogeny in AML Is Both Prognostic and Predictive in Patients Treated with Hypomethylating Agents Plus Venetoclax. Blood 2023, 142: 977. DOI: 10.1182/blood-2023-173935.Peer-Reviewed Original ResearchComposite complete response rateComposite complete responseHematopoietic cell transplantationAcute myeloid leukemiaDe novo groupHypomethylating agentsOverall survivalComplete responseTP53 mutationsPrognostic valueNewly diagnosed acute myeloid leukemiaAssociated with improved OSTreated with hypomethylating agentsTreated with intensive chemotherapyAllogeneic hematopoietic cell transplantationDiagnosed AMLMultivariate Cox regression modelConcurrent TP53 mutationLow-intensity regimensDiagnosed AML patientsLog-rank testRetrospective cohort studyMolecular ontogenyDe novo diseaseDana Farber Cancer InstituteSafety and Preliminary Efficacy of DFV890 in Adult Patients with Myeloid Diseases: A Phase 1b Study
Garcia-Manero G, Ooi M, Lao Z, Gill H, Abaza Y, Stahl M, Haque T, DeZern A, Greenberg P, Pelletier M, Singh A, Carreon D, Beaulieu V, Woo J. Safety and Preliminary Efficacy of DFV890 in Adult Patients with Myeloid Diseases: A Phase 1b Study. Blood 2023, 142: 3250. DOI: 10.1182/blood-2023-174642.Peer-Reviewed Original ResearchChronic myelomonocytic leukemiaCMML-specific prognostic scoring systemErythropoiesis-stimulating agentsDose-expansion partPrognostic Scoring SystemMyelodysplastic syndromeHypomethylating agentsLR-MDSEastern Cooperative Oncology Group performance statusIntermediate risk myelodysplastic syndromePredictive markers of efficacyDose of study treatmentInternational Prognostic Scoring SystemIL-18Colony-stimulating growth factorScoring systemAllogeneic hematopoietic transplantationBone marrow aspirate/biopsyPhase 1b studyProgression-free survivalTime to progressionPotential curative optionRisk myelodysplastic syndromesDuration of responseBone marrow assessment
2021
Venetoclax combination therapy in acute myeloid leukemia and myelodysplastic syndromes
Shimony S, Stone R, Stahl M. Venetoclax combination therapy in acute myeloid leukemia and myelodysplastic syndromes. Current Opinion In Hematology 2021, 29: 63-73. PMID: 34966123, DOI: 10.1097/moh.0000000000000698.Peer-Reviewed Original ResearchConceptsAcute myeloid leukemiaVenetoclax-based combination therapiesCombination therapyMyelodysplastic syndromeMyeloid leukemiaNewly diagnosed acute myeloid leukemiaAcute myeloid leukemia patientsVenetoclax combination therapyDeep molecular responseIncomplete count recoveryLow dose cytarabineBcl-2 inhibitorsHigh-risk populationRelapsed myelodysplastic syndromeProlonged cytopeniasDose cytarabineCount recoveryHypomethylating agentsRemission rateTargeted therapyTherapyBcl-2Therapeutic possibilitiesLong-term effectsPatient outcomes
2019
Immune Checkpoint Inhibitors in Acute Myeloid Leukemia: Novel Combinations and Therapeutic Targets
Stahl M, Goldberg A. Immune Checkpoint Inhibitors in Acute Myeloid Leukemia: Novel Combinations and Therapeutic Targets. Current Oncology Reports 2019, 21: 37. PMID: 30904967, DOI: 10.1007/s11912-019-0781-7.Peer-Reviewed Original ResearchConceptsAcute myeloid leukemiaImmune checkpoint inhibitionImmune checkpoint inhibitorsCheckpoint inhibitorsCheckpoint inhibitionHypomethylating agentsMyeloid leukemiaCombination of immune checkpoint inhibitionSuccess of immune checkpoint inhibitionClinical trialsEarly-phase clinical trialsCheckpoint inhibitor monotherapyMultiple clinical trialsCheckpoint therapyImmune checkpointsInhibitor monotherapyStandard therapySolid malignanciesImmune targetsTherapeutic efficacyClinical activityTherapeutic landscapeLeukemiaTherapeutic targetLeukemia cells
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