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-upTreatment 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