2022
A phase 1b study of venetoclax and azacitidine combination in patients with relapsed or refractory myelodysplastic syndromes
Zeidan AM, Borate U, Pollyea DA, Brunner AM, Roncolato F, Garcia JS, Filshie R, Odenike O, Watson AM, Krishnadasan R, Bajel A, Naqvi K, Zha J, Cheng W, Zhou Y, Hoffman D, Harb JG, Potluri J, Garcia‐Manero G. A phase 1b study of venetoclax and azacitidine combination in patients with relapsed or refractory myelodysplastic syndromes. American Journal Of Hematology 2022, 98: 272-281. PMID: 36309981, PMCID: PMC10100228, DOI: 10.1002/ajh.26771.Peer-Reviewed Original ResearchConceptsMedian overall survivalMyelodysplastic syndromeOverall survivalTransfusion independenceHematological improvementTherapy failureHigh-risk myelodysplastic syndromeInternational Working Group criteriaHematological adverse eventsPhase 1b studyRefractory myelodysplastic syndromeStandard of careEfficacy of venetoclaxEffective therapeutic strategyFebrile neutropeniaMarrow CROral venetoclaxComplete remissionAdverse eventsMedian durationAzacitidine treatmentMedian timeMarrow responseMulticenter studyGroup criteriaA phase 1b study of glasdegib + azacitidine in patients with untreated acute myeloid leukemia and higher-risk myelodysplastic syndromes
Sekeres MA, Schuster M, Joris M, Krauter J, Maertens J, Breems D, Gyan E, Kovacsovics T, Verma A, Vyas P, Wang ES, Ching K, O’Brien T, Gallo Stampino C, Ma WW, Kudla A, Chan G, Zeidan AM. A phase 1b study of glasdegib + azacitidine in patients with untreated acute myeloid leukemia and higher-risk myelodysplastic syndromes. Annals Of Hematology 2022, 101: 1689-1701. PMID: 35488900, DOI: 10.1007/s00277-022-04853-4.Peer-Reviewed Original ResearchConceptsAcute myeloid leukemiaHigh-risk myelodysplastic syndromePhase 1b studyChronic myelomonocytic leukemiaMyelodysplastic syndromeExpansion cohortSafety profileMDS cohortMyeloid leukemiaTreatment-emergent adverse eventsUntreated acute myeloid leukemiaNon-hematologic gradeMedian overall survivalAcceptable safety profileOverall response rateDrug-drug interactionsSafety cohortIntensive chemotherapyAdverse eventsOverall survivalClinical benefitQT prolongationAML cohortMyelomonocytic leukemiaGlasdegib
2021
Phase 3 VERONA study of venetoclax with azacitidine to assess change in complete remission and overall survival in treatment-naïve higher-risk myelodysplastic syndromes.
Zeidan A, Garcia J, Fenaux P, Platzbecker U, Miyazaki Y, Xiao Z, Zhou Y, Naqvi K, Kye S, Garcia-Manero G. Phase 3 VERONA study of venetoclax with azacitidine to assess change in complete remission and overall survival in treatment-naïve higher-risk myelodysplastic syndromes. Journal Of Clinical Oncology 2021, 39: tps7054-tps7054. DOI: 10.1200/jco.2021.39.15_suppl.tps7054.Peer-Reviewed Original ResearchHematopoietic stem cell transplantOverall survivalAcute myeloid leukemiaCR rateComplete remissionTransfusion independenceCell transplantationDisease progressionMyeloid leukemiaDay 1B-cell lymphoma-2 inhibitorRed blood cell transfusion independenceHigh-risk myelodysplastic syndromeAllogenic stem cell transplantationCo-morbid patientsIWG 2006 criteriaPhase 1b studyPlatelet transfusion independenceMedian overall survivalFirst-line treatmentPhase 3 studyBone marrow blastsDe novo patientsHematopoietic cell transplantationStudy days 1
2020
AML-187: The STIMULUS Clinical Trial Program: Evaluating Combination Therapy with MBG453 in Patients with Higher-Risk Myelodysplastic Syndrome (HR-MDS) or Acute Myeloid Leukemia
Zeidan A, Esteve J, Kim H, Miyazaki Y, Platzbecker U, Schuh A, Westermann J, Malek K, Scott J, Niolat J, Peyrard S, Kiertsman F, Stegert M, Fenaux P. AML-187: The STIMULUS Clinical Trial Program: Evaluating Combination Therapy with MBG453 in Patients with Higher-Risk Myelodysplastic Syndrome (HR-MDS) or Acute Myeloid Leukemia. Clinical Lymphoma Myeloma & Leukemia 2020, 20: s188. DOI: 10.1016/s2152-2650(20)30727-8.Peer-Reviewed Original ResearchHigh-risk myelodysplastic syndromeEvent-free survivalClinical trial programLeukemia-free survivalProgression-free survivalOverall survivalTrial programEligible patientsSecondary endpointsTransfusion independenceCombination therapyAnti-Tim-3 monoclonal antibodyCR/CRi rateMultiple immune cell typesHigher risk MDSMRD negative ratePhase 1b studyOpen-label studyComplete remission rateDouble-blind studyRelapse-free survivalGood safety profileAcute myeloid leukemiaImmune cell typesLeukemic stem cells
2019
A Phase 1b Study Evaluating the Safety and Efficacy of Venetoclax As Monotherapy or in Combination with Azacitidine for the Treatment of Relapsed/Refractory Myelodysplastic Syndrome
Zeidan A, Pollyea D, Garcia J, Brunner A, Roncolato F, Borate U, Odenike O, Bajel A, Watson A, Götze K, Nolte F, Tan P, Hong W, Dunbar M, Zhou Y, Gressick L, Ainsworth W, Harb J, Salem A, Hayslip J, Swords R, Garcia-Manero G. A Phase 1b Study Evaluating the Safety and Efficacy of Venetoclax As Monotherapy or in Combination with Azacitidine for the Treatment of Relapsed/Refractory Myelodysplastic Syndrome. Blood 2019, 134: 565. DOI: 10.1182/blood-2019-124994.Peer-Reviewed Original ResearchStock/stock optionsTreatment-emergent adverse eventsProgression-free survivalMedian progression-free survivalAbbVie IncOverall survivalFebrile neutropeniaStable diseaseMarrow blastsMyelodysplastic syndromeBcl-2 inhibitorsAstra ZenecaFrequent treatment-emergent adverse eventsInternational Working Group 2006 criteriaSerious treatment-emergent adverse eventsAllogeneic stem cell transplantationAdvisory CommitteeDaiichi SankyoCycles of AZACycles of decitabineECOG performance statusPhase 1b studyPhase 2 dosePredominant grade 3Refractory myelodysplastic syndromePS1023 MUTANT IDH1 INHIBITOR IVOSIDENIB (AG‐120) IN COMBINATION WITH AZACITIDINE FOR NEWLY DIAGNOSED ACUTE MYELOID LEUKEMIA
DiNardo C, Stein A, Stein E, Fathi A, Frankfurt O, Schuh A, Döhner H, Martinelli G, Patel P, Raffoux E, Tan P, Zeidan A, de Botton S, Kantarjian H, Stone R, Lam D, Wang X, Gong J, Kapsalis S, Hickman D, Zhang V, Winkler T, Wu B, Vyas P. PS1023 MUTANT IDH1 INHIBITOR IVOSIDENIB (AG‐120) IN COMBINATION WITH AZACITIDINE FOR NEWLY DIAGNOSED ACUTE MYELOID LEUKEMIA. HemaSphere 2019, 3: 460-461. DOI: 10.1097/01.hs9.0000562388.60660.bc.Peer-Reviewed Original ResearchAcute myeloid leukemiaOverall response rateMorphologic leukemia-free stateComplete remissionAdverse eventsFebrile neutropeniaCR rateMyeloid leukemiaMutant IDH1Isocitrate dehydrogenase 1Double-blind placebo-controlled studyGrade 3/4 adverse eventsRefractory acute myeloid leukemiaBone marrow mononuclear cellsCR/CRhGrade adverse eventsIDH differentiation syndromeIDH1 inhibitor ivosidenibMedian response durationPartial hematologic recoveryPhase 1b studyAbsolute neutrophil countPlacebo-controlled studyTreatment of adultsMarrow mononuclear cellsMutant 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
2017
A phase I trial of ipilimumab (ipi) in patients (pts) with myelodysplastic syndromes (MDS) after hypomethylating agent (HMAs) failure.
Zeidan A, Knaus H, Robinson T, Zeidner J, Blackford A, Rizzieri D, Frattini M, Levy M, Schroeder M, Ferguson A, Sheldon K, Dezern A, Gojo I, Gore S, Streicher H, Luznik L, Duffield A, Smith B. A phase I trial of ipilimumab (ipi) in patients (pts) with myelodysplastic syndromes (MDS) after hypomethylating agent (HMAs) failure. Journal Of Clinical Oncology 2017, 35: 7010-7010. DOI: 10.1200/jco.2017.35.15_suppl.7010.Peer-Reviewed Original ResearchImmune-related adverse eventsOverall survivalMyelodysplastic syndromeHMA failureDose levelsMarrow complete responsePhase 1b studyCTLA-4 blockadeMedian overall survivalImmune checkpoint blockadeKaplan-Meier methodPhase I trialPoor overall survivalExpression of ICOST cell activationDrug discontinuationHR-MDSStable diseaseSystemic steroidsAdverse eventsCheckpoint blockadeClinical responseMaintenance doseObjective responseAllogeneic transplantation
2015
Stabilization of Myelodysplastic Syndromes (MDS) Following Hypomethylating Agent (HMAs) Failure Using the Immune Checkpoint Inhibitor Ipilimumab: A Phase I Trial
Zeidan A, Zeidner J, Duffield A, Knaus H, Ferguson A, Sheldon K, DeZern A, Gojo I, Gore S, Streicher H, Luznik L, Smith B. Stabilization of Myelodysplastic Syndromes (MDS) Following Hypomethylating Agent (HMAs) Failure Using the Immune Checkpoint Inhibitor Ipilimumab: A Phase I Trial. Blood 2015, 126: 1666. DOI: 10.1182/blood.v126.23.1666.1666.Peer-Reviewed Original ResearchOverall survivalStable diseaseEnd of inductionMyelodysplastic syndromeFirst doseIpilimumab useMaintenance doseAnti-cytotoxic T-lymphocyte-associated protein 4 antibodyDose levelsInternational Working Group 2006 criteriaMedian white blood cell countImmune checkpoint inhibition therapyImmune checkpoint inhibitor ipilimumabMedian absolute neutrophil countAllogeneic stem cell transplantationWhite blood cell countT cell receptor repertoireBM blast percentageCheckpoint inhibitor ipilimumabDose-escalation partGrade 3 irAEsOngoing stable diseasePhase 1b studyProlonged disease stabilizationTolerability of ipilimumab