2024
Targeted therapies for myelodysplastic syndromes/neoplasms (MDS): current landscape and future directions
Bidikian A, Bewersdorf J, Shallis R, Getz T, Stempel J, Kewan T, Stahl M, Zeidan A. Targeted therapies for myelodysplastic syndromes/neoplasms (MDS): current landscape and future directions. Expert Review Of Anticancer Therapy 2024, 24: 1131-1146. PMID: 39367718, DOI: 10.1080/14737140.2024.2414071.Peer-Reviewed Original ResearchErythropoiesis-stimulating agentsTargeted therapyLR-MDSHR-MDSHypoxia-inducible factorAllogeneic hematopoietic stem cell transplantationLandscape of targeted therapiesHematopoietic stem cell transplantationHeterogeneous group of hematologic malignanciesGroup of hematologic malignanciesMolecular prognostic toolsDuration of responseStem cell transplantationTrial designClinical trial designHypomethylating agentsCell transplantationHematologic malignanciesImprove patient outcomesRNA splicing machineryImmune evasionPrognostic toolTGF-betaTherapyEffective treatment
2023
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
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 subpopulationsDurable Continuous Transfusion Independence (TI) with Imetelstat in IMerge Phase 3 for Patients with Heavily Transfused Non-Del(5q) Lower-Risk Myelodysplastic Syndromes (LR-MDS) Relapsed/Refractory (R/R) to or Ineligible for Erythropoiesis-Stimulating Agents (ESAs)
Platzbecker U, Komrokji R, Zeidan A, Fenaux P, Sekeres M, Savona M, Madanat Y, Jonášová A, Illmer T, Sherman L, Berry T, Riggs J, Xia Q, Navada S, Wan Y, Huang F, Feller F, Santini V. Durable Continuous Transfusion Independence (TI) with Imetelstat in IMerge Phase 3 for Patients with Heavily Transfused Non-Del(5q) Lower-Risk Myelodysplastic Syndromes (LR-MDS) Relapsed/Refractory (R/R) to or Ineligible for Erythropoiesis-Stimulating Agents (ESAs). Blood 2023, 142: 4605. DOI: 10.1182/blood-2023-181154.Peer-Reviewed Original ResearchLower-risk myelodysplastic syndromesErythropoiesis stimulating agentsPhase 3 trialTransfusion independenceVariant allele frequencyEnd pointTransfusion burdenAdverse eventsRed blood cell transfusionExploratory end pointsFrequent adverse eventsPrimary end pointRBC transfusion burdenReversible grade 3Secondary end pointsBlood cell transfusionDisease-modifying activityKaplan-Meier methodDuration of responseLoss of responseAdditional baseline characteristicsHigh telomerase activityCell transfusionBaseline characteristicsClinical response
2022
A randomized phase 2 trial of azacitidine with or without durvalumab as first-line therapy for older patients with AML
Zeidan AM, Boss I, Beach C, Copeland WB, Thompson E, Fox BA, Hasle VE, Hellmann A, Taussig D, Tormo M, Voso MT, Cavenagh J, O'Connor T, Previtali A, Rose S, Silverman LR. A randomized phase 2 trial of azacitidine with or without durvalumab as first-line therapy for older patients with AML. Blood Advances 2022, 6: 2219-2229. PMID: 34933333, PMCID: PMC9006260, DOI: 10.1182/bloodadvances.2021006138.Peer-Reviewed Original ResearchConceptsAcute myeloid leukemiaFirst-line therapyOlder patientsDay 1First-line combination therapyTreatment-emergent adverse eventsRandomized phase 2 trialSafety of durvalumabNew safety signalsPD-L1 expressionPhase 2 studyPhase 2 trialDuration of responseOverall response rateDurvalumab 1500Adverse eventsOverall survivalClinical efficacyCombination therapyMyeloid leukemiaSafety signalsTreatment responseCombination treatmentAzacitidineResponse rate
2020
Blast MRD AML-1 Trial: Blockade of PD-1 Added to Standard Therapy to Target Measurable Residual Disease in Acute Myeloid Leukemia (AML) 1- an Investigator-Initiated, CTEP-Sponsored, Randomized Phase 2 Study of the Anti-PD-1 Antibody Pembrolizumab in Combination with Conventional Intensive Chemotherapy (IC) As Frontline Therapy in Patients with Acute Myeloid Leukemia (AML)
Zeidan A, Boddu P, Wood B, Zelterman D, Little R, Ivy S, Caldwell A, Sanchez-Espiridion B, Alatrash G, Sharon E, Radich J. Blast MRD AML-1 Trial: Blockade of PD-1 Added to Standard Therapy to Target Measurable Residual Disease in Acute Myeloid Leukemia (AML) 1- an Investigator-Initiated, CTEP-Sponsored, Randomized Phase 2 Study of the Anti-PD-1 Antibody Pembrolizumab in Combination with Conventional Intensive Chemotherapy (IC) As Frontline Therapy in Patients with Acute Myeloid Leukemia (AML). Blood 2020, 136: 15. DOI: 10.1182/blood-2020-139668.Peer-Reviewed Original ResearchMRD-negative complete responsesAcute myeloid leukemiaMinimal residual diseaseEvent-free survivalImmune checkpoint inhibitionPhase 2 studyIntensive chemotherapyDuration of responseComplete responseOverall survivalPD-1AML patientsDay 1Free survivalHematologic improvementInitial treatmentStudy armsResidual diseaseDay IVLeukemia-specific T-cell responsesSingle-arm phase 2 studyPD-1/PD-L1 pathwayTherapy-related acute myeloid leukemiaCancer Therapy Evaluation ProgramImmune cell subsets analysisBlast MRD AML-2: Blockade of PD-1 Added to Standard Therapy to Target Measurable Residual Disease (MDR) in Acute Myeloid Leukemia (AML) 2- a Randomized Phase 2 Study of the Venetoclax, Azacitidine, and Pembrolizumab Versus Venetoclax and Azacitidine As First Line Therapy in Older Patients with AML Who Are Ineligible or Who Refuse Intensive Chemotherapy
Zeidan A, Boddu P, Wood B, Zelterman D, Little R, Ivy S, Caldwell A, Sanchez-Espiridion B, Alatrash G, Sharon E, Radich J. Blast MRD AML-2: Blockade of PD-1 Added to Standard Therapy to Target Measurable Residual Disease (MDR) in Acute Myeloid Leukemia (AML) 2- a Randomized Phase 2 Study of the Venetoclax, Azacitidine, and Pembrolizumab Versus Venetoclax and Azacitidine As First Line Therapy in Older Patients with AML Who Are Ineligible or Who Refuse Intensive Chemotherapy. Blood 2020, 136: 11-12. DOI: 10.1182/blood-2020-139752.Peer-Reviewed Original ResearchEvent-free survivalDuration of responseMRD-negative CRIntensive chemotherapyOverall survivalDay 1Complete remissionFree survivalHematologic improvementOlder patientsSecondary AMLPD-1Study armsAML patientsInitial treatmentHematologic disordersLeukemia-specific T-cell responsesCancer Therapy Evaluation ProgramCR/complete remissionImmune cell subsets analysisRandomized phase 2 studyRandomized phase 2 trialRandomized phase II studyAllogeneic stem cell transplantBetter long-term clinical outcomesEffect 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