2024
Initial Results from the QTc Substudy of the IMerge Phase 3 Trial Demonstrate Clinically Meaningful Efficacy, Manageable Safety, and Absence of Proarrhythmic Risk in Patients with Lower-Risk Myelodysplastic Syndromes Who Received Prior Therapies Beyond Erythropoiesis Stimulating Agents
Komrokji R, Santini V, Platzbecker U, Van Eygen K, Diez-Campelo M, De Paz R, Sanz G, Thépot S, Kaźmierczak M, Oliva E, Sekeres M, Fenaux P, Madanat Y, Savona M, Riggs J, Dougherty S, Lennox A, Xia Q, Sun L, Berry T, Zeidan A. Initial Results from the QTc Substudy of the IMerge Phase 3 Trial Demonstrate Clinically Meaningful Efficacy, Manageable Safety, and Absence of Proarrhythmic Risk in Patients with Lower-Risk Myelodysplastic Syndromes Who Received Prior Therapies Beyond Erythropoiesis Stimulating Agents. Blood 2024, 144: 4590-4590. DOI: 10.1182/blood-2024-200885.Peer-Reviewed Original ResearchLower-risk myelodysplastic syndromesErythropoiesis-stimulating agentsHematological improvement-erythroidFood and Drug AdministrationRBC-TIPhase 3 trialPlacebo recipientsHypomethylating agentsInternational Working GroupData cutoffMyelodysplastic syndromeTransfusion reductionRed blood cellsProarrhythmic riskProgression to acute myeloid leukemiaErythropoiesis-stimulating agent useConcentration-QT relationshipEffects of imetelstatRBC transfusion independenceGrade 3/4 neutropeniaMedian treatment durationKaplan-Meier methodologyClinically meaningful efficacyUnited States Food and Drug AdministrationAcute myeloid leukemia
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
2019
Clinical Benefit of Glasdegib in Combination with Azacitidine or Low-Dose Cytarabine in Patients with Acute Myeloid Leukemia
Zeidan A, Schuster M, Krauter J, Maertens J, Gyan E, Joris M, Menne T, Vyas P, Wendy W, O'Connell A, Zeremski M, Kudla A, Chan G, Sekeres M. Clinical Benefit of Glasdegib in Combination with Azacitidine or Low-Dose Cytarabine in Patients with Acute Myeloid Leukemia. Blood 2019, 134: 3916. DOI: 10.1182/blood-2019-124034.Peer-Reviewed Original ResearchTreatment-emergent adverse eventsAcute myeloid leukemiaLow-dose cytarabineMedian treatment durationIntensive chemotherapyOverall survivalPersonal feesMyelodysplastic syndromeDose delaysSpeakers bureauMedian followMyeloid leukemiaTreatment durationSerious treatment-emergent adverse eventsRandomized phase 3 trialMonths median overall survivalNon-financial supportAdvisory CommitteeSeattle GeneticsDaiichi SankyoIncomplete hematologic recoveryOlder unfit patientsMedian overall survivalSuperior overall survivalAbsolute neutrophil countAssessment of Longer-Term Efficacy and Safety in the Phase 3, Randomized, Double-Blind, Placebo-Controlled MEDALIST Trial of Luspatercept to Treat Anemia in Patients (Pts) with Revised International Prognostic Scoring System (IPSS-R) Very Low-, Low-, or Intermediate-Risk Myelodysplastic Syndromes (MDS) with Ring Sideroblasts (RS) Who Require Red Blood Cell (RBC) Transfusions
Fenaux P, Mufti G, Buckstein R, Santini V, Díez-Campelo M, Finelli C, Cazzola M, Ilhan O, Sekeres M, Komrokji R, List A, Zeidan A, Verma A, Laadem A, Ito R, Zhang J, Rampersad A, Sinsimer D, Linde P, Garcia-Manero G, Platzbecker U. Assessment of Longer-Term Efficacy and Safety in the Phase 3, Randomized, Double-Blind, Placebo-Controlled MEDALIST Trial of Luspatercept to Treat Anemia in Patients (Pts) with Revised International Prognostic Scoring System (IPSS-R) Very Low-, Low-, or Intermediate-Risk Myelodysplastic Syndromes (MDS) with Ring Sideroblasts (RS) Who Require Red Blood Cell (RBC) Transfusions. Blood 2019, 134: 841. DOI: 10.1182/blood-2019-123064.Peer-Reviewed Original ResearchErythropoiesis-stimulating agentsIntermediate-risk myelodysplastic syndromesRBC-TIClinical benefitMyelodysplastic syndromeData cutoffHighest dose levelTransfusion burdenCelgene CorporationRing sideroblastsSpeakers bureauMedian durationDose levelsInternational Working Group 2006 criteriaClass erythroid maturation agentGrade 1Red blood cell transfusionInternational Prognostic Scoring SystemLower-risk myelodysplastic syndromesAdvisory CommitteeLow-risk MDSRBC transfusion independenceRegular RBC transfusionsMedian treatment durationBlood cell transfusionA Phase 1b Study of Glasdegib in Combination with Azacitidine in Patients with Untreated Higher-Risk Myelodysplastic Syndromes, Acute Myeloid Leukemia, and Chronic Myelomonocytic Leukemia
Sekeres M, Schuster M, Joris M, Krauter J, Maertens J, Gyan E, Kovacsovics T, Verma A, Vyas P, Wang E, Wendy W, Zeremski M, Kudla A, Chan G, Zeidan A. A Phase 1b Study of Glasdegib in Combination with Azacitidine in Patients with Untreated Higher-Risk Myelodysplastic Syndromes, Acute Myeloid Leukemia, and Chronic Myelomonocytic Leukemia. Blood 2019, 134: 177. DOI: 10.1182/blood-2019-124050.Peer-Reviewed Original ResearchHigh-risk myelodysplastic syndromeChronic myelomonocytic leukemiaAcute myeloid leukemiaLow-dose cytarabineMedian treatment durationComplete remissionPhase 1b trialIntensive chemotherapyOverall survivalMyelodysplastic syndromePersonal feesAdverse eventsMyelomonocytic leukemiaSpeakers bureauSerious TEAEsFebrile neutropeniaMedian ageMedian timeEuropean LeukemiaNetRisk categoriesMyeloid leukemiaMedian (95% CI) OSMortality rateTreatment durationCR/complete remission