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
2023
Impact of Symptom Benefit and Transfusion Response on Survival in Myelofibrosis Patients Treated with Pacritinib: PERSIST-2 Landmark Survival Analysis
Ajufo H, Bewersdorf J, Harrison C, Palandri F, Mascarenhas J, Palmer J, Gerds A, Kiladjian J, Buckley S, Derkach A, Roman-Torres K, Rampal R. Impact of Symptom Benefit and Transfusion Response on Survival in Myelofibrosis Patients Treated with Pacritinib: PERSIST-2 Landmark Survival Analysis. Blood 2023, 142: 3207. DOI: 10.1182/blood-2023-177643.Peer-Reviewed Original ResearchLandmark survival analysisOverall survivalMyelofibrosis patientsNon-respondersTransfusion independenceRed blood cellsSymptom scoresOS benefitPERSIST-2Associated with OS benefitAssociated with improved OSRed blood cell transfusionAssociated with improved survivalSymptom benefitSurvival analysisEfficacy assessment periodSpleen volume reductionMedian platelet countLog-rank testMeasures of clinical benefitBAT armTotal symptom scoreUnique survival advantagesSymptom burden reductionAnemia improvement
2021
Clinical effectiveness of DNA methyltransferase inhibitors and lenalidomide in older patients with refractory anemia with ring sideroblasts: a population-based study in the United States
Wang X, Zeidan AM, Wang R, Bewersdorf JP, Zhang C, Podoltsev NA, Huntington SF, Gore SD, Ma X. Clinical effectiveness of DNA methyltransferase inhibitors and lenalidomide in older patients with refractory anemia with ring sideroblasts: a population-based study in the United States. Leukemia & Lymphoma 2021, 62: 2438-2447. PMID: 33899659, DOI: 10.1080/10428194.2021.1913142.Peer-Reviewed Original ResearchConceptsPopulation-based studyDNA methyltransferase inhibitorRARS patientsRefractory anemiaRing sideroblastsRed blood cell transfusion independenceEnd Results-Medicare databaseLower-risk myelodysplastic syndromesPopulation-based cohortMethyltransferase inhibitorRBC-TIMedian durationMedian survivalOlder patientsTransfusion independenceTreatment initiationMyelodysplastic syndromeClinical effectivenessBetter survivalLenalidomideTreatment groupsPatientsRS statusOlder adultsAnemia
2020
Clinical outcomes of older patients with AML receiving hypomethylating agents: a large population-based study in the United States
Zeidan AM, Wang R, Wang X, Shallis RM, Podoltsev NA, Bewersdorf JP, Huntington SF, Neparidze N, Giri S, Gore SD, Davidoff AJ, Ma X. Clinical outcomes of older patients with AML receiving hypomethylating agents: a large population-based study in the United States. Blood Advances 2020, 4: 2192-2201. PMID: 32433746, PMCID: PMC7252544, DOI: 10.1182/bloodadvances.2020001779.Peer-Reviewed Original ResearchConceptsAcute myeloid leukemiaDecitabine-treated patientsTransfusion independenceRed blood cell transfusion independenceLarge population-based studyOlder AML patientsRBC transfusion independenceEnd Results-MedicarePopulation-based studyStandard of careAgent azacitidineMedian survivalOlder patientsIntensive therapyAML patientsClinical outcomesClinical benefitMyeloid leukemiaMortality riskPatientsAzacitidineDecitabineOlder adultsOne-thirdMeaningful differences
2019
Clinical Outcomes of Older Patients (pts) with Acute Myeloid Leukemia (AML) Receiving Hypomethylating Agents (HMAs): A Large Population-Based Study in the United States
Zeidan A, Wang R, Wang X, Shallis R, Podoltsev N, Bewersdorf J, Huntington S, Neparidze N, Giri S, Gore S, Davidoff A, Ma X. Clinical Outcomes of Older Patients (pts) with Acute Myeloid Leukemia (AML) Receiving Hypomethylating Agents (HMAs): A Large Population-Based Study in the United States. Blood 2019, 134: 646. DOI: 10.1182/blood-2019-127398.Peer-Reviewed Original ResearchRBC transfusion dependenceAcute myeloid leukemiaMedian overall survivalTransfusion independenceOverall survivalTransfusion dependenceHypomethylating agentCelgene CorporationHMA initiationIntensive chemotherapyOS probabilityMedian timeMultivariable analysisMultivariable Cox proportional hazards modelsBoehringer IngelheimAdvisory CommitteeCox proportional hazards modelDaiichi SankyoChemotherapy-related hospitalizationMo of diagnosisRBC transfusion independenceImproved overall survivalClinical trial evidenceInferior overall survivalWorse overall survival