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 studyOutcomes of Patients with IDH1/2 Mutated Accelerated/Blast-Phase Myeloproliferative Neoplasms in the Era of IDH Inhibitors
Goldberg L, Yoon J, Johnston H, Davidson M, Siddon A, Shallis R, Chen E, Burkart M, Oh T, Iyer S, Madarang E, Muthiah C, Kassner J, Rampal R, Guru Murthy G, Bradley T, Abaza Y, Garcia J, Gupta V, Pettit K, Odenike O, Cursio J, Patel A. Outcomes of Patients with IDH1/2 Mutated Accelerated/Blast-Phase Myeloproliferative Neoplasms in the Era of IDH Inhibitors. Blood 2024, 144: 1787-1787. DOI: 10.1182/blood-2024-197898.Peer-Reviewed Original ResearchIsocitrate dehydrogenase inhibitorsMedian OSMPN-AP/BPIntensive chemotherapyMyeloproliferative neoplasmsHypomethylating agentsEuropean LeukemiaNetAcute myeloid leukemiaMPN-BPComplete remissionOverall survivalCytogenetic responsePartial remissionBlast phaseTen ptsCo-mutationsIncidence of driver mutationsVariable risk of progressionAchievement of complete remissionAllogeneic stem cell transplantationAssociated with poor overall survivalCohort of ptsIDH1 inhibitor ivosidenibIDH2 inhibitor enasidenibIncomplete count recoveryClinical Outcomes and Variability Based on Baseline Cytogenetic Risk of Patients with MDS Treated with Hypomethylating Agents: An Analysis from the International Consortium for MDS (icMDS) Validate Database
Getz T, Kewan T, Bewersdorf J, Stempel J, Lanino L, Wei W, Al Ali N, DeZern A, Sekeres M, Uy G, Carraway H, Desai P, Griffiths E, Stein E, Brunner A, McMahon C, Shallis R, Zeidner J, Savona M, Ball S, Chandhok N, Logothetis C, Bidikian A, Roboz G, Rolles B, Wang E, Harris A, Amaya M, Hawkins H, Grenet J, Xie Z, Madanat Y, Abaza Y, Badar T, Haferlach T, Maciejewski J, Sallman D, Enjeti A, Al-Rabi K, Halahleh K, Hiwase D, Diez-Campelo M, Valcarcel D, Haferlach C, Pleyer L, Kotsianidis I, Pappa V, Santini V, Consagra A, Al-Kali A, Ogawa S, Nannya Y, Stahl M, Della Porta M, Komrokji R, Zeidan A. Clinical Outcomes and Variability Based on Baseline Cytogenetic Risk of Patients with MDS Treated with Hypomethylating Agents: An Analysis from the International Consortium for MDS (icMDS) Validate Database. Blood 2024, 144: 3219-3219. DOI: 10.1182/blood-2024-202075.Peer-Reviewed Original ResearchNon-complex karyotypeInternational Prognostic Scoring SystemCytogenetic risk groupHMA initiationComplex karyotypeIPSS-RHypomethylating agentsOverall survivalRisk groupsCytogenetic abnormalitiesAllogeneic hematopoietic stem cell transplantationHematopoietic stem cell transplantationAssociated with worse survivalHypomethylating agent combinationsPoor-risk cytogeneticsPeripheral blood blastsTreated with azacitidinePrognostic Scoring SystemMeasured overall survivalStem cell transplantationKaplan-Meier methodLog-rank testOutcomes of PTTime-to-event analysisRisk of patientsLeukemia Physician's Perspective on Transplant in Patients with TP53 Mutated Acute Myeloid Leukemia
Moreno Vanegas Y, El Khatib S, Hisrich B, Coltoff A, Shallis R, Patel A, Bewersdorf J, Oh T, Abaza Y, Foucar C, Goldberg A, Duvall A, Atallah E, Litzow M, Badar T. Leukemia Physician's Perspective on Transplant in Patients with TP53 Mutated Acute Myeloid Leukemia. Blood 2024, 144: 1487-1487. DOI: 10.1182/blood-2024-205782.Peer-Reviewed Original ResearchAcute myeloid leukemiaTP53-mAllo-HCTComplex cytogeneticsHypomethylating agentsInternational Consensus ClassificationRefractory diseaseSecondary AMLOverall survivalMyeloid leukemiaTP53-mutated acute myeloid leukemiaDe novo acute myeloid leukemiaProgressive acute myeloid leukemiaSecondary acute myeloid leukemiaAllogeneic hematopoietic cell transplantationMedian overall survivalTP53 allelic stateIncomplete count recoveryLow-intensity regimensReviewed electronic medical recordsHematopoietic cell transplantationRate of relapseMulticenter observational studyOverall response ratePatient selection criteriaAssociation between Body Mass Index and Outcomes in Patients with Newly Diagnosed Acute Myeloid Leukemia Treated with Hypomethylating Agents and Venetoclax
Weiss J, Yates S, Badar T, Patel A, Winer E, Litzow M, Cheng W, Lin C, Shallis R. Association between Body Mass Index and Outcomes in Patients with Newly Diagnosed Acute Myeloid Leukemia Treated with Hypomethylating Agents and Venetoclax. Blood 2024, 144: 1489-1489. DOI: 10.1182/blood-2024-206670.Peer-Reviewed Original ResearchAcute myeloid leukemiaBody mass indexOverall response rateBody mass index groupsSecondary AMLObese ptsHypomethylating agentsEuropean LeukemiaNetMulti-centerOverall survivalMyeloid leukemiaRetrospective studyMass indexNewly diagnosed acute myeloid leukemiaVariable volume of distributionSecondary acute myeloid leukemiaAssociated with higher 90-day mortalityTreatment of acute myeloid leukemiaHigher 30-day mortalityMultivariate Cox regression modelInterquartile rangeComposite remission rateExtensive protein bindingKaplan-Meier methodRisk of early mortalityImpact of Time from Diagnosis to Treatment on Outcomes of Adults with AML Treated with HMA and Venetoclax: A US-Based, Multi-Center, Real-World, Retrospective Analysis from the Consortium on Myeloid Malignancies and Neoplastic Diseases (COMMAND)
Yates S, Weiss J, Sneider A, Geramita E, Guru Murthy G, Badar T, Im A, Lin C, Cheng W, Winer E, Abaza Y, Litzow M, Atallah E, Swaroop A, Patel A, Shallis R. Impact of Time from Diagnosis to Treatment on Outcomes of Adults with AML Treated with HMA and Venetoclax: A US-Based, Multi-Center, Real-World, Retrospective Analysis from the Consortium on Myeloid Malignancies and Neoplastic Diseases (COMMAND). Blood 2024, 144: 447-447. DOI: 10.1182/blood-2024-207116.Peer-Reviewed Original ResearchDiagnosed AMLAcute myeloid leukemiaEuropean LeukemiaNetOverall survivalComplete responseECOG PSHypomethylating agentsSeverity of presentationMulti-centerPerformance statusRetrospective analysisFactors associated with improved OSTherapy-related acute myeloid leukemiaECOG PS of 2Initiation of induction therapyMultivariate analysisAssociated with worse OSNext generation sequencing panelIntermediate risk diseaseIncomplete count recoveryECOG performance statusDisease biologyNPM1 mutation statusUnivariate Cox modelPre-planned subgroup analysisClinical Utilization and Outcomes of Hypomethylating Agents and Venetoclax in Patients with Myelodysplastic Syndrome - a Multicenter Retrospective Analysis
Guru Murthy G, Ball S, Feld J, Abboud R, Haddadin M, Patel S, Kishtagari A, Hawkins H, Guerra V, Dworkin E, Tawfiq R, Dulak D, Feng A, Cotte C, Cohen-Nowak A, Shukla A, Balasubramanian S, Winer E, Foucar C, Abaza Y, Shallis R, Lin C, Badar T, Patel A, Im A, Szabo A, Atallah E. Clinical Utilization and Outcomes of Hypomethylating Agents and Venetoclax in Patients with Myelodysplastic Syndrome - a Multicenter Retrospective Analysis. Blood 2024, 144: 3206-3206. DOI: 10.1182/blood-2024-211623.Peer-Reviewed Original ResearchHMA monotherapyTumor lysis syndromePhase 3 randomized clinical trialEvent free survivalHypomethylating agentsMulticenter retrospective analysisMyelodysplastic syndromeAdverse eventsUS academic medical centersClinical trialsUpfront settingFree survivalOverall survivalClinical outcomesRetrospective analysisClinical management of myelodysplastic syndromesIncidence of tumor lysis syndromeAcademic medical centerManagement of myelodysplastic syndromesAllogeneic stem cell transplantationSingle arm clinical trialResponse rateOutpatient settingStem cell transplantationMedical CenterTargeted 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 treatmentIntensive 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 patientsCombination 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 ResearchHypomethylating 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 treatmentClinical 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 study