2024
Ziftomenib Combined with Intensive Induction (7+3) in Newly Diagnosed NPM1- m or KMT2A -r Acute Myeloid Leukemia: Interim Phase 1a Results from KOMET-007
Zeidan A, Wang E, Issa G, Erba H, Altman J, Balasubramanian S, Strickland S, Roboz G, Schiller G, McMahon C, Palmisiano N, Madanat Y, Rotta M, Nadiminti K, Wei H, Riches M, Corum D, Leoni M, Dale S, Fathi A. Ziftomenib Combined with Intensive Induction (7+3) in Newly Diagnosed NPM1- m or KMT2A -r Acute Myeloid Leukemia: Interim Phase 1a Results from KOMET-007. Blood 2024, 144: 214-214. DOI: 10.1182/blood-2024-198218.Peer-Reviewed Original ResearchDose-limiting toxicityMinimal residual diseaseAcute myeloid leukemiaMedian time to neutrophil recoveryDays to platelet recoveryMinimal residual disease negativityDecreased neutrophil countKMT2A-rDecreased platelet countNPM1 mutationsAdverse eventsCRC ratesDose levelsNeutrophil recoveryData cutoffQTc prolongationPlatelet recoveryPlatelet countMyeloid leukemiaNeutrophil countDifferentiation syndromeClinical activityCycle 1 day 8Persistent acute myeloid leukemiaStandard dose of cytarabineZiftomenib Combined with Venetoclax/Azacitidine in Relapsed/Refractory NPM1 -m or KMT2A -r Acute Myeloid Leukemia: Interim Phase 1a Results from KOMET-007
Fathi A, Issa G, Wang E, Erba H, Altman J, Balasubramanian S, Roboz G, Schiller G, McMahon C, Palmisiano N, Juckett M, Madanat Y, Rotta M, Pratz K, Yaghmour G, Nadiminti K, Wei H, Riches M, Corum D, Leoni M, Dale S, Zeidan A. Ziftomenib Combined with Venetoclax/Azacitidine in Relapsed/Refractory NPM1 -m or KMT2A -r Acute Myeloid Leukemia: Interim Phase 1a Results from KOMET-007. Blood 2024, 144: 2880-2880. DOI: 10.1182/blood-2024-199170.Peer-Reviewed Original ResearchAcute myeloid leukemiaDecreased neutrophil countDecreased platelet countNPM1 mutationsKMT2A-rAdverse eventsCRC ratesClinical activityR/R patientsData cutoffQTc prolongationPlatelet countMyeloid leukemiaNucleophosmin 1Neutrophil countDifferentiation syndromeComposite complete remission rateCycle 1 day 8R/R acute myeloid leukemiaTreatment-emergent adverse eventsDose of venetoclaxInhibitor-naive patientsDose-escalation cohortsDose-expansion phaseComplete remission rate
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 inhibitorEffect of enasidenib (ENA) plus azacitidine (AZA) on complete remission and overall response versus AZA monotherapy in mutant -IDH2 ( mIDH2 ) newly diagnosed acute myeloid leukemia (ND-AML).
Dinardo C, Schuh A, Stein E, Montesinos P, Wei A, De Botton S, Zeidan A, Fathi A, Quek L, Kantarjian H, Frattini M, Lersch F, Gong J, Franovic A, Vyas P, Dohner H. Effect of enasidenib (ENA) plus azacitidine (AZA) on complete remission and overall response versus AZA monotherapy in mutant -IDH2 ( mIDH2 ) newly diagnosed acute myeloid leukemia (ND-AML). Journal Of Clinical Oncology 2020, 38: 7501-7501. DOI: 10.1200/jco.2020.38.15_suppl.7501.Peer-Reviewed Original ResearchOverall response rateDuration of responseGrade 3Randomized phase I/II studyPhase I/II studyResponse rateIDH differentiation syndromePoor-risk cytogeneticsComplete remission rateIntermediate-risk cytogeneticsEvent-free survivalPhase II portionImproved response ratesAcute myeloid leukemiaMost common reasonsMutant IDH2AZA monotherapyDifferentiation syndromeECOG PSFebrile neutropeniaIntensive chemotherapyMedian EFSMedian OSPt ageComplete remission
2019
Mutant IDH1 inhibitor ivosidenib (IVO; AG-120) in combination with azacitidine (AZA) for newly diagnosed acute myeloid leukemia (ND AML).
Dinardo C, Stein A, Stein E, Fathi A, Frankfurt O, Schuh A, Martinelli G, Patel P, Raffoux E, Tan P, Zeidan A, de Botton S, Kantarjian H, Stone R, Lam D, Gong J, Zhang V, Winkler T, Wu B, Vyas P. Mutant IDH1 inhibitor ivosidenib (IVO; AG-120) in combination with azacitidine (AZA) for newly diagnosed acute myeloid leukemia (ND AML). Journal Of Clinical Oncology 2019, 37: 7011-7011. DOI: 10.1200/jco.2019.37.15_suppl.7011.Peer-Reviewed Original ResearchAdverse eventsECG QTFebrile neutropeniaDouble-blind placebo-controlled studyGrade 3/4 adverse eventsBone marrow mononuclear cellsCR/CRhGrade adverse eventsIDH differentiation syndromeIDH1 inhibitor ivosidenibMedian response durationNon-intensive therapyPartial hematologic recoveryPhase 1b studyPlacebo-controlled studyAcute myeloid leukemiaMarrow mononuclear cellsAZA monotherapyD1-7Differentiation syndromeData cutoffHematologic recoveryMedian durationMedian timeSafety profile