2024
Phase Ib Study of PRT543, an Oral Protein Arginine Methyltransferase 5 (PRMT5) Inhibitor, in Patients with Relapsed or Refractory, Splicing Factor-Mutant Myeloid Malignancies
Bewersdorf J, Mi X, Lu B, Kuykendall A, Sallman D, Patel M, Stevens D, Philipovskiy A, Sutamtewagul G, Masarova L, Keiffer G, Verma A, Bhagwat N, Heiser D, Ro S, Hong W, Abdel-Wahab O, Stein E. Phase Ib Study of PRT543, an Oral Protein Arginine Methyltransferase 5 (PRMT5) Inhibitor, in Patients with Relapsed or Refractory, Splicing Factor-Mutant Myeloid Malignancies. Blood 2024, 144: 3215. DOI: 10.1182/blood-2024-198495.Peer-Reviewed Original ResearchTreatment-emergent adverse eventsPlatelet transfusion independenceProtein arginine methyltransferase 5Myeloid malignanciesSplicing factor mutationsSymmetric dimethyl arginineMedian PFSTransfusion independenceFollow-upOpen-label phase Ib studyRed blood cell transfusion-dependentPRMT5 inhibitionAdequate end-organ functionBaseline serum EPO levelsRecommended phase 2 doseMedian duration of treatmentGrade 5 eventsLower-risk MDSMDS/MPN overlap syndromesPhase 2 doseIntensive induction chemotherapyPeripheral blood mononuclear cellsHigh-risk MDSPhase Ib studyMedian follow-upMis-Splicing Derived Neoantigens and Cognate T Cell Receptors in Splicing Factor Mutant Myeloid Neoplasms
Kim W, Crosse E, De Neef E, Etxeberria I, Sabio E, Wang E, Bewersdorf J, Lu S, Belleville A, Fox N, Castro C, Zhang P, Fujino T, Lewis J, Rahman J, Zhang B, Winick J, Lewis A, Stanley R, Dewolf S, Meskauskaite Urben B, Takizawa M, Krause T, Molina H, Chaligne R, Koppikar P, Molldrem J, Gigoux M, Merghoub T, Daniyan A, Greenbaum B, Klebanoff C, Bradley R, Abdel-Wahab O. Mis-Splicing Derived Neoantigens and Cognate T Cell Receptors in Splicing Factor Mutant Myeloid Neoplasms. Blood 2024, 144: 343-343. DOI: 10.1182/blood-2024-198639.Peer-Reviewed Original ResearchCD8+ T cellsT cell receptorPrimary human T cellsHuman T cellsT cellsHLA-ILeukemic cellsSRSF2 mutationsHealthy donorsIsolated CD8+ T cellsGraft-versus-leukemia effectT cell cytotoxic functionTCR-T cell therapyVirus-reactive T cellsAllogeneic stem cell transplantationT cell-based immunotherapyT cell receptor clonotypesLyse leukemic cellsPatient PBMC samplesCognate T cell receptorsDonor T cellsHigh-risk MDSStem cell transplantationHLA class IMis-splicingTreatment of Myelodysplastic Syndromes for Older Patients: Current State of Science, Challenges, and Opportunities
Kewan T, Stahl M, Bewersdorf J, Zeidan A. Treatment of Myelodysplastic Syndromes for Older Patients: Current State of Science, Challenges, and Opportunities. Current Hematologic Malignancy Reports 2024, 19: 138-150. PMID: 38632155, DOI: 10.1007/s11899-024-00733-y.Peer-Reviewed Original ResearchHematopoietic stem cell transplantationAllogeneic hematopoietic stem cell transplantationLower-risk MDSErythropoiesis-stimulating agentsHypomethylating agentsIPSS-MHR-MDSRisk stratificationMolecular International Prognostic Scoring SystemRisk of leukemia progressionTreated with hypomethylating agentsInternational Prognostic Scoring SystemTreatment of myelodysplastic syndromesOral hypomethylating agentsHigh-risk MDSPrognostic Scoring SystemStem cell transplantationEnhanced risk stratificationRecent FindingsRecent advancesRefine treatment strategiesQuality-of-life improvementAssociated with treatmentTreatment decision-makingIntensive chemotherapyMDS patients
2023
Consensus proposal for revised International Working Group 2023 response criteria for higher-risk myelodysplastic syndromes
Zeidan A, Platzbecker U, Bewersdorf J, Stahl M, Adès L, Borate U, Bowen D, Buckstein R, Brunner A, Carraway H, Daver N, Díez-Campelo M, de Witte T, DeZern A, Efficace F, Garcia-Manero G, Garcia J, Germing U, Giagounidis A, Griffiths E, Hasserjian R, Hellström-Lindberg E, Iastrebner M, Komrokji R, Kulasekararaj A, Malcovati L, Miyazaki Y, Odenike O, Santini V, Sanz G, Scheinberg P, Stauder R, van de Loosdrecht A, Wei A, Sekeres M, Fenaux P. Consensus proposal for revised International Working Group 2023 response criteria for higher-risk myelodysplastic syndromes. Blood 2023, 141: 2047-2061. PMID: 36724453, DOI: 10.1182/blood.2022018604.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsHigh-risk MDSComplete remissionResponse criteriaInternational Working GroupClinical trialsHigh-risk myelodysplastic syndromeEnd pointMarrow complete remissionPartial hematologic recoveryClinical end pointsPatient-centered outcomesNovel investigational drugsVariable clinical presentationEvent end pointsHemoglobin thresholdHematologic recoveryCount recoveryClinical presentationClinical benefitMyelodysplastic syndromeIWG criteriaMyelodysplastic neoplasmsConsensus recommendationsInvestigational drugsNew agents
2021
The development and clinical use of oral hypomethylating agents in acute myeloid leukemia and myelodysplastic syndromes: dawn of the total oral therapy era
Schiffer M, Zhao J, Johnson A, Lee J, Bewersdorf JP, Zeidan AM. The development and clinical use of oral hypomethylating agents in acute myeloid leukemia and myelodysplastic syndromes: dawn of the total oral therapy era. Expert Review Of Anticancer Therapy 2021, 21: 989-1002. PMID: 33853476, DOI: 10.1080/14737140.2021.1918002.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsChronic myelomonocytic leukemiaAcute myeloid leukemiaMyelodysplastic syndromeMyeloid leukemiaMyelomonocytic leukemiaHypomethylating agentAllogeneic hematopoietic cell transplantPost-transplant maintenance therapyAcute myeloid leukemia (AML) treatmentHematopoietic cell transplantHigh-risk MDSMyeloid leukemia treatmentPotential combination therapyCC-486Induction chemotherapyOral azacitidineTherapy eraMaintenance therapyOral agentsAdult patientsCell transplantClinical benefitMaintenance treatmentCombination therapyPredictive biomarkers