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-up
2019
One plus one does not always equal two, especially with regard to hypomethylating agents: the question of synergy of azacitidine and lenalidomide for treatment of relapsed acute myeloid leukemia and myelodysplastic syndromes post allogeneic hematopoietic stem cell transplant
Bewersdorf JP, Stahl M, Zeidan AM. One plus one does not always equal two, especially with regard to hypomethylating agents: the question of synergy of azacitidine and lenalidomide for treatment of relapsed acute myeloid leukemia and myelodysplastic syndromes post allogeneic hematopoietic stem cell transplant. Expert Review Of Hematology 2019, 12: 575-578. PMID: 31225770, DOI: 10.1080/17474086.2019.1635005.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsMeSH KeywordsAntigens, CDAzacitidineCD8-Positive T-LymphocytesClinical Trials as TopicDrug Therapy, CombinationFemaleHematopoietic Stem Cell TransplantationHumansLenalidomideLeukemia, Myeloid, AcuteLymphocyte Activation Gene 3 ProteinMaleMiddle AgedMyelodysplastic SyndromesProgrammed Cell Death 1 ReceptorRecurrenceTransplantation, HomologousConceptsAcute myeloid leukemiaHematopoietic stem cell transplantStem cell transplantMyelodysplastic syndromeMyeloid leukemiaAllo-HSCTCell transplantAllogeneic hematopoietic stem cell transplantResponse rateAllogeneic stem cell transplantationNovel salvage therapiesPhase Ib studyStem cell transplantationOverall response rateCycles of treatmentCases of graftHigh response rateMechanism of actionCombination lenalidomideSalvage therapyHost diseaseMost patientsCurative treatmentCombination therapyDisease stage