2024
Differentiation syndrome associated with treatment with IDH2 inhibitor enasidenib: pooled analysis from clinical trials
Montesinos P, Fathi A, de Botton S, Stein E, Zeidan A, Zhu Y, Prebet T, Vigil C, Bluemmert I, Yu X, DiNardo C. Differentiation syndrome associated with treatment with IDH2 inhibitor enasidenib: pooled analysis from clinical trials. Blood Advances 2024, 8: 2509-2519. PMID: 38507688, PMCID: PMC11131052, DOI: 10.1182/bloodadvances.2023011914.Peer-Reviewed Original ResearchAcute myeloid leukemiaDevelopment of differentiation syndromeRisk factorsPooled analysisIDH2-mutant acute myeloid leukemiaClinical trialsAcute myeloid leukemia populationMedian time to onsetClinical features of DSBone marrow blastsNon-specific symptomsTime to onsetBaseline risk factorsTreatment of DSSymptoms of DSIdentified risk factorsFeatures of DSMarrow blastsSystemic steroidsPulmonary infiltratesClinical responseMutant IDH2 inhibitorMyeloid leukemiaClinical featuresGrade 3
2023
Imetelstat in patients with lower-risk myelodysplastic syndromes who have relapsed or are refractory to erythropoiesis-stimulating agents (IMerge): a multinational, randomised, double-blind, placebo-controlled, phase 3 trial
Platzbecker U, Santini V, Fenaux P, Sekeres M, Savona M, Madanat Y, Díez-Campelo M, Valcárcel D, Illmer T, Jonášová A, Bělohlávková P, Sherman L, Berry T, Dougherty S, Shah S, Xia Q, Sun L, Wan Y, Huang F, Ikin A, Navada S, Feller F, Komrokji R, Zeidan A. Imetelstat in patients with lower-risk myelodysplastic syndromes who have relapsed or are refractory to erythropoiesis-stimulating agents (IMerge): a multinational, randomised, double-blind, placebo-controlled, phase 3 trial. The Lancet 2023, 403: 249-260. PMID: 38048786, DOI: 10.1016/s0140-6736(23)01724-5.Peer-Reviewed Original ResearchLower-risk myelodysplastic syndromesErythropoiesis-stimulating agentsPlacebo groupAdverse eventsMyelodysplastic syndromeGrade 3Subsequent anti-cancer therapyTreatment-emergent adverse eventsTreatment-emergent grade 3Days of randomisationIPSS risk groupRBC transfusion burdenTransfusion independence rateTreatment-related deathsUnacceptable toxic effectsPlacebo-controlled trialDisease-modifying activityPhase 2 trialPhase 3 trialPrimary efficacy analysisProportion of patientsWithdrawal of consentUnmet medical needComputer-generated scheduleAnti-cancer therapyBlinatumomab in Combination with Immune Checkpoint Inhibitors (ICIs) of PD-1 and CTLA-4 in Adult Patients with Relapsed/Refractory (R/R) CD19 Positive B-Cell Acute Lymphoblastic Leukemia (ALL): Results of a Phase I Study
Webster J, Luskin M, Rimando J, Blackford A, Zeidan A, Sharon E, Streicher H, DeAngelo D, Luznik L, Gojo I. Blinatumomab in Combination with Immune Checkpoint Inhibitors (ICIs) of PD-1 and CTLA-4 in Adult Patients with Relapsed/Refractory (R/R) CD19 Positive B-Cell Acute Lymphoblastic Leukemia (ALL): Results of a Phase I Study. Blood 2023, 142: 966. DOI: 10.1182/blood-2023-191109.Peer-Reviewed Original ResearchImmune checkpoint inhibitorsMixed phenotype acute leukemiaRelapse-free survivalOverall survivalAcute lymphoblastic leukemiaComplete remissionPD-1Checkpoint inhibitorsExtramedullary diseaseAdverse eventsBM blastsGrade 3Positive B-cell acute lymphoblastic leukemiaResponse rateImmune-related adverse eventsB-cell acute lymphoblastic leukemiaMulti-center phase IPhase IDose-escalation schemaNon-hematologic toxicitiesMedian overall survivalDose-escalation studyPD-L1 expressionDuration of responseT cell subpopulationsCharacterization and Management of Cytopenias after Imetelstat Treatment in the IMerge Phase 3 Trial of Patients with Lower-Risk Myelodysplastic Syndromes (LR-MDS)
Zeidan A, Savona M, Madanat Y, Fenaux P, Komrokji R, Jonášová A, Illmer T, Sun L, Berry T, Feller F, Navada S, Santini V, Platzbecker U. Characterization and Management of Cytopenias after Imetelstat Treatment in the IMerge Phase 3 Trial of Patients with Lower-Risk Myelodysplastic Syndromes (LR-MDS). Blood 2023, 142: 6478. DOI: 10.1182/blood-2023-180962.Peer-Reviewed Original ResearchTreatment-emergent adverse eventsLower-risk myelodysplastic syndromesPhase 3 trialManagement of cytopeniasGrade 3Placebo groupDose adjustmentMedian timeTreatment delayDose reductionInternational Prognostic Scoring System risk groupsHematologic treatment-emergent adverse eventsRed blood cell transfusion dependencyImetelstat treatmentExperienced grade 3RBC transfusion burdenRBC transfusion independenceTreatment cycles 1Grade 4 neutropeniaGrade 4 thrombocytopeniaPrimary end pointGrowth factor supportErythropoiesis-stimulating agentsCycle 1High telomerase activity
2022
A randomized phase 2 trial of azacitidine with or without durvalumab as first-line therapy for higher-risk myelodysplastic syndromes
Zeidan AM, Boss I, Beach C, Copeland WB, Thompson E, Fox BA, Hasle VE, Ogasawara K, Cavenagh J, Silverman LR, Voso MT, Hellmann A, Tormo M, O'Connor T, Previtali A, Rose S, Garcia-Manero G. A randomized phase 2 trial of azacitidine with or without durvalumab as first-line therapy for higher-risk myelodysplastic syndromes. Blood Advances 2022, 6: 2207-2218. PMID: 34972214, PMCID: PMC9006291, DOI: 10.1182/bloodadvances.2021005487.Peer-Reviewed Original ResearchConceptsHigh-risk myelodysplastic syndromeAdverse eventsArm BArm ASubcutaneous azacitidineMyelodysplastic syndromeTreatment cyclesRandomized phase 2 trialInhibitory immune checkpoint moleculesHematologic adverse eventsMedian overall survivalFirst-line therapyFirst-line treatmentPhase 2 studyPhase 2 trialImmune checkpoint moleculesOverall response rateBone marrow granulocytesAzacitidine monotherapyIntravenous durvalumabCheckpoint moleculesOverall survivalClinical outcomesMarrow granulocytesGrade 3
2020
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).
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
Enasidenib Plus Azacitidine Significantly Improves Complete Remission and Overall Response Compared with Azacitidine Alone in Patients with Newly Diagnosed Acute Myeloid Leukemia (AML) with Isocitrate Dehydrogenase 2 (IDH2) Mutations: Interim Phase II Results from an Ongoing, Randomized Study
DiNardo C, Schuh A, Stein E, Fernandez P, Wei A, De Botton S, Zeidan A, Fathi A, Quek L, Kantarjian H, Frattini M, Lersch F, Gong J, Franovic A, MacBeth K, Vyas P, Döhner H. Enasidenib Plus Azacitidine Significantly Improves Complete Remission and Overall Response Compared with Azacitidine Alone in Patients with Newly Diagnosed Acute Myeloid Leukemia (AML) with Isocitrate Dehydrogenase 2 (IDH2) Mutations: Interim Phase II Results from an Ongoing, Randomized Study. Blood 2019, 134: 643. DOI: 10.1182/blood-2019-130362.Peer-Reviewed Original ResearchOverall response rateAcute myeloid leukemiaDuration of responseMorphologic leukemia-free stateBone marrow mononuclear cellsAZA armComplete remissionIntensive chemotherapyCelgene CorporationResponse rateDaiichi SankyoVariant allele frequencySpeakers bureauPTC TherapeuticsPartial remissionData cutoffGrade 3Phase I/II studyMedian DORAdvisory CommitteeSeattle GeneticsForty-sevenConventional care regimensIDH differentiation syndromePoor-risk cytogenetics
2015
Results of a Phase 2 Trial of High Dose Lenalidomide Monotherapy in Patients with Relapsed/Refractory Higher-Risk Myelodysplastic Syndromes or Acute Myeloid Leukemia with Trilineage Dysplasia
Zeidan A, Smith B, Carraway H, Gojo I, Sakoian S, Gore S, DeZern A. Results of a Phase 2 Trial of High Dose Lenalidomide Monotherapy in Patients with Relapsed/Refractory Higher-Risk Myelodysplastic Syndromes or Acute Myeloid Leukemia with Trilineage Dysplasia. Blood 2015, 126: 2901. DOI: 10.1182/blood.v126.23.2901.2901.Peer-Reviewed Original ResearchHigh-risk myelodysplastic syndromeOverall hematologic response rateHigh-dose lenalidomideCycles of lenalidomideNon-hematologic toxicitiesAcute myeloid leukemiaOverall survivalTrilineage dysplasiaEntire cohortMyelodysplastic syndromePlatelet countGrade 3Myeloid leukemiaInternational Working Group 2006 criteriaJohns Hopkins Institutional Review BoardMedian white blood cell countSingle-arm phase II studyBone marrow blast percentageUnderwent bone marrow transplantationWhite blood cell countPhase 2 clinical trialHematologic response rateHigher risk MDSPoor-risk karyotypeCycles of therapy
2013
HLA-Haploidentical Donor Lymphocyte Infusions for Patients with Relapsed Hematologic Malignancies after Related HLA-Haploidentical Bone Marrow Transplantation
Zeidan AM, Forde PM, Symons H, Chen A, Smith BD, Pratz K, Carraway H, Gladstone DE, Fuchs EJ, Luznik L, Jones RJ, Bolaños-Meade J. HLA-Haploidentical Donor Lymphocyte Infusions for Patients with Relapsed Hematologic Malignancies after Related HLA-Haploidentical Bone Marrow Transplantation. Transplantation And Cellular Therapy 2013, 20: 314-318. PMID: 24296490, PMCID: PMC4010132, DOI: 10.1016/j.bbmt.2013.11.020.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAdultAgedAntineoplastic Agents, AlkylatingBone Marrow TransplantationChildChild, PreschoolCyclophosphamideFemaleGraft vs Host DiseaseHaplotypesHLA AntigensHumansLeukemia, Myeloid, AcuteLymphocyte TransfusionLymphomaMaleMiddle AgedRecurrenceRemission InductionSurvival AnalysisT-LymphocytesTransplantation ConditioningTransplantation, IsogeneicConceptsPost-transplantation cyclophosphamideDonor lymphocyte infusionBone marrow transplantationComplete responseLymphocyte infusionMarrow transplantationT-cell-replete bone marrow transplantationHLA-haploidentical bone marrow transplantationRelapsed hematologic malignanciesTreatment of relapseCells/Acute myeloid leukemiaAcute GVHDChronic GVHDAcceptable toxicityHost diseaseDurable responsesMedian durationMedian ageNonmyeloablative conditioningMedian timeEntire cohortHematologic malignanciesMyeloid leukemiaGrade 3