2022
Efficacy of FLT3 and IDH1/2 inhibitors in patients with acute myeloid leukemia previously treated with venetoclax
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. Efficacy of FLT3 and IDH1/2 inhibitors in patients with acute myeloid leukemia previously treated with venetoclax. Leukemia Research 2022, 122: 106942. PMID: 36108424, DOI: 10.1016/j.leukres.2022.106942.Peer-Reviewed Original ResearchConceptsAcute myeloid leukemiaIDH2 inhibitorsMyeloid leukemiaResponse rateRetrospective cohort studyOverall response rateRAS pathway mutationsNovel therapeutic strategiesMedian OSR AMLCohort studyShorter OSLandmark trialsTargeted agentsFrontline treatmentMutant FLT3Combination therapyTreatment optionsIDH1/2 inhibitorsDisease progressionTherapeutic strategiesPatientsSmall molecule inhibitorsVenetoclaxTherapyIn vivo anti-tumor effect of PARP inhibition in IDH1/2 mutant MDS/AML resistant to targeted inhibitors of mutant IDH1/2
Gbyli R, Song Y, Liu W, Gao Y, Biancon G, Chandhok NS, Wang X, Fu X, Patel A, Sundaram R, Tebaldi T, Mamillapalli P, Zeidan AM, Flavell RA, Prebet T, Bindra RS, Halene S. In vivo anti-tumor effect of PARP inhibition in IDH1/2 mutant MDS/AML resistant to targeted inhibitors of mutant IDH1/2. Leukemia 2022, 36: 1313-1323. PMID: 35273342, PMCID: PMC9103411, DOI: 10.1038/s41375-022-01536-x.Peer-Reviewed Original ResearchConceptsAcute myeloid leukemiaMyelodysplastic syndromeMDS/acute myeloid leukemiaRefractory acute myeloid leukemiaPARP inhibitionVivo anti-tumor effectsAlternate therapeutic optionsSubset of AMLAnti-tumor effectsPre-clinical studiesRibose polymerase inhibitorsSerial transplantation assaysHomologous recombination defectsTherapeutic optionsTreatment optionsOverall engraftmentHigh relapseIDH inhibitionMyeloid leukemiaIsocitrate dehydrogenase 1Small molecule inhibitorsCell frequencyXeno-graftsIDH1/2 mutationsMalignant transformation
2020
Mutant 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 inhibitor
2015
The clinical use of DNA methyltransferase inhibitors in myelodysplastic syndromes
Zahr A, Aldin E, Barbarotta L, Podoltsev N, Zeidan AM. The clinical use of DNA methyltransferase inhibitors in myelodysplastic syndromes. Expert Review Of Anticancer Therapy 2015, 15: 1019-1036. PMID: 26292903, DOI: 10.1586/14737140.2015.1061936.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsMeSH KeywordsDisease ProgressionDNA (Cytosine-5-)-MethyltransferasesEnzyme InhibitorsEpigenesis, GeneticHumansMyelodysplastic SyndromesSurvival RateConceptsHigh-risk myelodysplastic syndromeRisk myelodysplastic syndromesMyelodysplastic syndromeDNA methyltransferase inhibitorClinical useAllogeneic hematopoietic cell transplantationHematopoietic cell transplantationAcute myeloid leukemiaMethyltransferase inhibitorFull therapeutic potentialOverall survivalPeripheral cytopeniasCurative treatmentCell transplantationDismal outcomeTreatment optionsMyeloid leukemiaIneffective hematopoiesisOnly interventionTherapeutic potentialHematopoietic malignanciesHeterogeneous groupPatientsSyndromeInhibitors