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 treatmentToward a more patient‐centered drug development process in clinical trials for patients with myelodysplastic syndromes/neoplasms (MDS): Practical considerations from the International Consortium for MDS (icMDS)
Efficace F, Buckstein R, Abel G, Giesinger J, Fenaux P, Bewersdorf J, Brunner A, Bejar R, Borate U, DeZern A, Greenberg P, Roboz G, Savona M, Sparano F, Boultwood J, Komrokji R, Sallman D, Xie Z, Sanz G, Carraway H, Taylor J, Nimer S, Della Porta M, Santini V, Stahl M, Platzbecker U, Sekeres M, Zeidan A. Toward a more patient‐centered drug development process in clinical trials for patients with myelodysplastic syndromes/neoplasms (MDS): Practical considerations from the International Consortium for MDS (icMDS). HemaSphere 2024, 8: e69. PMID: 38774655, PMCID: PMC11106800, DOI: 10.1002/hem3.69.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsPatient-reported outcomesPatient-reported outcome dataHealth-related qualityPatient-reported outcome endpointsHealth-related quality of lifeClinical trialsImprove patients' health-related qualityPatients' health-related qualityPatient-reported outcome itemsQuality of lifeTime-to-event analysisRandomized controlled trialsTreatment decision-makingPatient carePatient populationTreatment advancesControlled trialsPatientsIncurable diseaseAssessment strategiesHRQoLBenefit/risk assessmentDrug development processTrialsTherapy
2023
Current landscape of translational and clinical research in myelodysplastic syndromes/neoplasms (MDS): Proceedings from the 1st International Workshop on MDS (iwMDS) Of the International Consortium for MDS (icMDS)
Bewersdorf J, Xie Z, Bejar R, Borate U, Boultwood J, Brunner A, Buckstein R, Carraway H, Churpek J, Daver N, Porta M, DeZern A, Fenaux P, Figueroa M, Gore S, Griffiths E, Halene S, Hasserjian R, Hourigan C, Kim T, Komrokji R, Kuchroo V, List A, Loghavi S, Majeti R, Odenike O, Patnaik M, Platzbecker U, Roboz G, Sallman D, Santini V, Sanz G, Sekeres M, Stahl M, Starczynowski D, Steensma D, Taylor J, Abdel-Wahab O, Xu M, Savona M, Wei A, Zeidan A. Current landscape of translational and clinical research in myelodysplastic syndromes/neoplasms (MDS): Proceedings from the 1st International Workshop on MDS (iwMDS) Of the International Consortium for MDS (icMDS). Blood Reviews 2023, 60: 101072. PMID: 36934059, DOI: 10.1016/j.blre.2023.101072.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsImmune checkpoint inhibitorsSpecific molecular alterationsNovel animal modelInnate immune systemCheckpoint inhibitorsImmune dysregulationMDS patientsClinical trialsNovel therapiesTherapeutic strategiesAnimal modelsGermline predispositionImmune systemMolecular alterationsClinical researchInternational ConsortiumNeoplasmsClinical workGenetic landscapeInternational WorkshopPatientsCurrent landscapePathogenesisTherapyDisease
2022
Prognostic implications of mono-hit and multi-hit TP53 alterations in patients with acute myeloid leukemia and higher risk myelodysplastic syndromes treated with azacitidine-based therapy
Zeidan A, Bewersdorf J, Hasle V, Shallis R, Thompson E, de Menezes D, Rose S, Boss I, Halene S, Haferlach T, Fox B. Prognostic implications of mono-hit and multi-hit TP53 alterations in patients with acute myeloid leukemia and higher risk myelodysplastic syndromes treated with azacitidine-based therapy. Leukemia 2022, 37: 240-243. PMID: 36437356, DOI: 10.1038/s41375-022-01766-z.Peer-Reviewed Original ResearchPredictors of Long-Term Outcome in TP53-Mutated Acute Myeloid Leukemia Patients Receiving Allogeneic Stem Cell Transplant after First- or Second-Line Therapy: Results from the Consortium on Myeloid Malignancies and Neoplastic Diseases (COMMAND)
Badar T, Atallah E, Shallis R, Saliba A, Stahl M, Bewersdorf J, Grenet J, Patel A, Abaza Y, Murthy S, Duvall A, Burkart M, Palmisiano N, Kubiak M, Kota V, Dinner S, Goldberg A, Litzow M. Predictors of Long-Term Outcome in TP53-Mutated Acute Myeloid Leukemia Patients Receiving Allogeneic Stem Cell Transplant after First- or Second-Line Therapy: Results from the Consortium on Myeloid Malignancies and Neoplastic Diseases (COMMAND). Blood 2022, 140: 1435-1437. DOI: 10.1182/blood-2022-167731.Peer-Reviewed Original ResearchThe Characteristics and Prognosis of Patients with Clonal Cytopenias of Undetermined Significance, Including Cancer and Therapy-Related Clonal Cytopenias
Xie Z, Smith A, Komrokji R, Al Ali N, Patel A, Saygin C, Zeidan A, Bewersdorf J, Kishtagari A, Zeidner J, Coombs C, Madanat Y, Foran J, Badar T, Desai P, Tsai C, Griffiths E, Al Malki M, Amanam I, Lai C, Deeg J, Ades L, Yi C, Osman A, Dinner S, Abaza Y, Chandhok N, Soong D, Taylor J, Brunner A, Carraway H, Singh A, Geyer S, Padron E, Patnaik M, Savona M, Al-Kali A. The Characteristics and Prognosis of Patients with Clonal Cytopenias of Undetermined Significance, Including Cancer and Therapy-Related Clonal Cytopenias. Blood 2022, 140: 2887-2890. DOI: 10.1182/blood-2022-162367.Peer-Reviewed Original ResearchMolecular predictors of immunophenotypic measurable residual disease clearance in acute myeloid leukemia
Stahl M, Derkach A, Farnoud N, Bewersdorf J, Robinson T, Famulare C, Cho C, Devlin S, Menghrajani K, Patel M, Cai S, Miles L, Bowman R, Geyer M, Dunbar A, Epstein‐Peterson Z, McGovern E, Schulman J, Glass J, Taylor J, Viny A, Stein E, Getta B, Arcila M, Gao Q, Barker J, Shaffer B, Papadopoulos E, Gyurkocza B, Perales M, Abdel‐Wahab O, Levine R, Giralt S, Zhang Y, Xiao W, Pai N, Papaemmanuil E, Tallman M, Roshal M, Goldberg A. Molecular predictors of immunophenotypic measurable residual disease clearance in acute myeloid leukemia. American Journal Of Hematology 2022, 98: 79-89. PMID: 36251406, PMCID: PMC10080561, DOI: 10.1002/ajh.26757.Peer-Reviewed Original ResearchConceptsMeasurable residual diseaseAcute myeloid leukemiaAllo-SCTInduction chemotherapyPersistent diseaseMyeloid leukemiaAllogeneic stem cell transplantationStem cell transplantationMonosomy 5Residual diseaseDisease clearanceKaryotypic abnormalitiesPrognostic factorsCell transplantationMolecular predictorsMRD clearanceRemissionClinical trialsNext-generation sequencingChemotherapyPatientsMutation patternsTherapyLeukemiaMRDVenetoclax-based salvage therapy in patients with relapsed/refractory acute myeloid leukemia previously treated with FLT3 or IDH1/2 inhibitors
Bewersdorf JP, Shallis RM, Derkach A, Goldberg AD, Stein A, Stein EM, Marcucci G, Zeidan AM, Shimony S, DeAngelo DJ, Stone RM, Aldoss I, Ball BJ, Stahl M. Venetoclax-based salvage therapy in patients with relapsed/refractory acute myeloid leukemia previously treated with FLT3 or IDH1/2 inhibitors. Leukemia & Lymphoma 2022, 64: 188-196. PMID: 36287540, PMCID: PMC9905301, DOI: 10.1080/10428194.2022.2136952.Peer-Reviewed Original ResearchConceptsAcute myeloid leukemiaSalvage therapyIDH1/2 inhibitorsIDH2 inhibitorsMyeloid leukemiaResponse rateRefractory acute myeloid leukemiaEffective salvage therapyLow-dose cytarabineMedian overall survivalRetrospective cohort studyOverall response rateLow response rateCohort studyOverall survivalAML patientsTreatment optionsFLT3 inhibitorsITD mutationPatientsTherapyFLT3Little dataVenetoclaxInhibitorsEfficacy of FLT3 and IDH1/2 inhibitors in patients with acute myeloid leukemia previously treated with venetoclax
Bewersdorf JP, Shallis RM, Derkach A, Goldberg AD, Stein A, Stein EM, Marcucci G, Zeidan AM, Shimony S, DeAngelo DJ, Stone RM, Aldoss I, Ball BJ, Stahl M. Efficacy of FLT3 and IDH1/2 inhibitors in patients with acute myeloid leukemia previously treated with venetoclax. Leukemia Research 2022, 122: 106942. PMID: 36108424, DOI: 10.1016/j.leukres.2022.106942.Peer-Reviewed Original ResearchConceptsAcute myeloid leukemiaIDH2 inhibitorsMyeloid leukemiaResponse rateRetrospective cohort studyOverall response rateRAS pathway mutationsNovel therapeutic strategiesMedian OSR AMLCohort studyShorter OSLandmark trialsTargeted agentsFrontline treatmentMutant FLT3Combination therapyTreatment optionsIDH1/2 inhibitorsDisease progressionTherapeutic strategiesPatientsSmall molecule inhibitorsVenetoclaxTherapyInvestigational venetoclax combination therapy in acute myeloid leukemia – a systematic review and meta-analysis
Shimony S, Rozental A, Bewersdorf J, Goldberg A, Stein E, Grimshaw A, Stone R, DeAngelo D, Wolach O, Stahl M. Investigational venetoclax combination therapy in acute myeloid leukemia – a systematic review and meta-analysis. Haematologica 2022, 107: 2955-2960. PMID: 36453519, PMCID: PMC9713559, DOI: 10.3324/haematol.2022.281453.Peer-Reviewed Original ResearchTranslating recent advances in the pathogenesis of acute myeloid leukemia to the clinic
Bewersdorf J, Abdel-Wahab O. Translating recent advances in the pathogenesis of acute myeloid leukemia to the clinic. Genes & Development 2022, 36: 259-277. PMID: 35318270, PMCID: PMC8973851, DOI: 10.1101/gad.349368.122.Peer-Reviewed Original ResearchConceptsAcute myeloid leukemiaMyeloid leukemiaAnti-Tim-3 antibodiesPathogenesis of acute myeloid leukemiaTargeting of acute myeloid leukemiaMolecular targeted approachesUnmet medical needAnti-CD47IDH1/2 inhibitorsHematologic malignanciesSplicing factor mutationsCellular therapyPreclinical meansImmune targetsTET2</i>FDA approvalTrispecific antibodyMenin inhibitionMedical needLeukemiaAntibodiesIDH1/2MalignancyTherapyPatients
2021
Venetoclax-based combinations in AML and high-risk MDS prior to and following allogeneic hematopoietic cell transplant
Bewersdorf JP, Derkach A, Gowda L, Menghrajani K, DeWolf S, Ruiz JD, Ponce DM, Shaffer BC, Tamari R, Young JW, Jakubowski AA, Gyurkocza B, Chan A, Xiao W, Glass J, King AC, Cai SF, Daniyan A, Famulare C, Cuello BM, Podoltsev NA, Roshal M, Giralt S, Perales MA, Seropian S, Cho C, Zeidan AM, Prebet T, Stein EM, Tallman MS, Goldberg AD, Stahl M. Venetoclax-based combinations in AML and high-risk MDS prior to and following allogeneic hematopoietic cell transplant. Leukemia & Lymphoma 2021, 62: 3394-3401. PMID: 34477024, PMCID: PMC9012492, DOI: 10.1080/10428194.2021.1966788.Peer-Reviewed Original ResearchConceptsAcute myeloid leukemiaAllogeneic hematopoietic cell transplantAllo-HCTHematopoietic cell transplantSalvage therapyMyelodysplastic syndromeCell transplantMemorial Sloan-Kettering Cancer CenterHigh-risk myelodysplastic syndromeSecond allo-HCTSalvage treatment optionOverall response rateMedian followMedian OSVenetoclax therapyRetrospective studyCancer CenterTreatment optionsOS estimatesMyeloid leukemiaPatientsResponse rateTherapyTransplantMonthsBiTEs, DARTS, BiKEs and TriKEs—Are Antibody Based Therapies Changing the Future Treatment of AML?
Allen C, Zeidan AM, Bewersdorf JP. BiTEs, DARTS, BiKEs and TriKEs—Are Antibody Based Therapies Changing the Future Treatment of AML? Life 2021, 11: 465. PMID: 34071099, PMCID: PMC8224808, DOI: 10.3390/life11060465.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsAcute myeloid leukemiaAntibody-based therapiesBispecific antibodiesSide effectsMalignant cellsBispecific T-cell engagersCytokine release syndromeCommon side effectsLeukemia-associated antigensT-cell engagersEarly encouraging resultsRelease syndromeGemtuzumab ozogamicinTreatment landscapeAML treatmentCell engagersAntigen escapeMyeloid leukemiaT cellsImmune responseFuture treatmentTherapyAntibodiesTreatmentCellsChallenges in the Evaluation and Management of Toxicities Arising From Immune Checkpoint Inhibitor Therapy for Patients With Myeloid Malignancies
Shallis RM, Bewersdorf JP, Swoboda DM, Wei W, Gowda L, Prebet T, Halene S, Pillai MM, Parker T, Neparidze N, Podoltsev NA, Seropian S, Sallman DA, Gore SD, Zeidan AM. Challenges in the Evaluation and Management of Toxicities Arising From Immune Checkpoint Inhibitor Therapy for Patients With Myeloid Malignancies. Clinical Lymphoma Myeloma & Leukemia 2021, 21: e483-e487. PMID: 33551344, DOI: 10.1016/j.clml.2021.01.003.Peer-Reviewed Original Research
2020
Immune checkpoint inhibition in myeloid malignancies: Moving beyond the PD-1/PD-L1 and CTLA-4 pathways
Bewersdorf JP, Shallis RM, Zeidan AM. Immune checkpoint inhibition in myeloid malignancies: Moving beyond the PD-1/PD-L1 and CTLA-4 pathways. Blood Reviews 2020, 45: 100709. PMID: 32487480, DOI: 10.1016/j.blre.2020.100709.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsImmune checkpoint inhibitorsMyeloid malignanciesPD-1/PD-L1CTLA-4 pathwayImmune checkpoint inhibitionAcute myeloid leukemiaSafe combination therapyICI therapyImmunologic landscapeCheckpoint inhibitorsDisease coursePD-L1Checkpoint inhibitionMyelodysplastic syndromeCombination therapyMechanisms of resistanceClinical trialsMyeloid leukemiaClinical developmentPotential biomarkersNovel targetPatientsMalignancyTherapyBiomarkers
2019
The golden age for patients in their golden years: The progressive upheaval of age and the treatment of newly-diagnosed acute myeloid leukemia
Shallis RM, Boddu PC, Bewersdorf JP, Zeidan AM. The golden age for patients in their golden years: The progressive upheaval of age and the treatment of newly-diagnosed acute myeloid leukemia. Blood Reviews 2019, 40: 100639. PMID: 31761380, DOI: 10.1016/j.blre.2019.100639.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsInduction therapyAcute myeloid leukemia patientsMost acute myeloid leukemia (AML) patientsAML patients ageIntensive induction therapyLeukemic stem cell persistenceOptimal treatment modalityMyeloid leukemia patientsPatient-specific factorsAcute myeloid leukemiaAvailability of therapiesMedical comorbiditiesOlder patientsPatient ageIntensive therapyOrgan reserveTreatment algorithmEarly mortalityLongstanding recommendationsTreatment modalitiesSuch therapyLeukemia patientsMyeloid leukemiaPatientsTherapyHedgehog pathway inhibition as a therapeutic target in acute myeloid leukemia
Shallis RM, Bewersdorf JP, Boddu PC, Zeidan AM. Hedgehog pathway inhibition as a therapeutic target in acute myeloid leukemia. Expert Review Of Anticancer Therapy 2019, 19: 717-729. PMID: 31422721, DOI: 10.1080/14737140.2019.1652095.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsAcute myeloid leukemiaHh pathway inhibitorsMyeloid leukemiaSurvival of AMLPathway inhibitorHh pathwayPoor-risk diseaseHedgehog pathway inhibitionStem cellsCombination therapyClinical trialsFirst approvalTherapeutic strategiesTherapeutic targetPathway inhibitionHematopoietic stem cellsNeoplasm therapyOlder populationTherapyHedgehog pathwayFurther studiesLeukemiaNormal hematopoiesisAdult stem cellsInhibitorsEpigenetic therapy combinations in acute myeloid leukemia: what are the options?
Bewersdorf JP, Shallis R, Stahl M, Zeidan AM. Epigenetic therapy combinations in acute myeloid leukemia: what are the options? Therapeutic Advances In Hematology 2019, 10: 2040620718816698. PMID: 30719265, PMCID: PMC6348528, DOI: 10.1177/2040620718816698.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsAcute myeloid leukemiaCombination therapyTherapy combinationsMyeloid leukemiaEpigenetic therapyAdvanced clinical testingTherapeutic optionsClinical trialsConventional chemotherapyClinical dataPreclinical studiesAML pathogenesisClinical practiceSingle agentClinical testingTherapyLeukemic pathogenesisDriver mutationsDNA methylationHistone methylation inhibitorPathogenesisLeukemiaDehydrogenase inhibitorEpigenetic alterationsActual DNA sequence