A multicenter phase Ib trial of the histone deacetylase inhibitor entinostat in combination with pembrolizumab in patients with myelodysplastic syndromes/neoplasms or acute myeloid leukemia refractory to hypomethylating agents
Bewersdorf J, Shallis R, Sharon E, Park S, Ramaswamy R, Roe C, Irish J, Caldwell A, Wei W, Yacoub A, Madanat Y, Zeidner J, Altman J, Odenike O, Yerrabothala S, Kovacsovics T, Podoltsev N, Halene S, Little R, Piekarz R, Gore S, Kim T, Zeidan A. A multicenter phase Ib trial of the histone deacetylase inhibitor entinostat in combination with pembrolizumab in patients with myelodysplastic syndromes/neoplasms or acute myeloid leukemia refractory to hypomethylating agents. Annals Of Hematology 2023, 103: 105-116. PMID: 38036712, DOI: 10.1007/s00277-023-05552-4.Peer-Reviewed Original ResearchConceptsDose-limiting toxicityAcute myeloid leukemiaMarrow complete remissionPhase Ib trialAdverse eventsIb trialDose escalationNCI Cancer Therapy Evaluation ProgramAcute myeloid leukemia refractoryHematologic adverse eventsProtocol-defined responseDose level 1Anti-PD1 therapyAnti-PD1 antibodyDose-escalation designLimited clinical efficacySystems immunology approachHistone deacetylase inhibitor entinostatLeukemia refractoryMCR patientsComplete remissionRespiratory failureSuppressor cellsEscalation designClinical efficacyA phase I study of ruxolitinib in combination with abemaciclib for patients with primary or post-polycythemia vera/essential thrombocythemia myelofibrosis.
Bewersdorf J, Verstovsek S, Derkach A, Masarova L, Pemmaraju N, Stein E, Mauro M, Rampal R, Bose P. A phase I study of ruxolitinib in combination with abemaciclib for patients with primary or post-polycythemia vera/essential thrombocythemia myelofibrosis. Journal Of Clinical Oncology 2023, 41: tps7086-tps7086. DOI: 10.1200/jco.2023.41.16_suppl.tps7086.Peer-Reviewed Original ResearchCDK4/6 inhibitorsSymptom scoresPhase I dose-escalation trialMedian overall survivalMD Anderson Cancer CenterDose-escalation designDuration of responseMaximum tolerated doseSafety of ruxolitinibSpleen volume reductionBiomarkers of responseHigh-risk diseasePhase I studyTreated with increasing dosesDose of ruxolitinibOral Janus kinaseLeft costal marginJanus kinase inhibitorsCDK4/6 inhibitor abemaciclibIncreased expression of CDC25AMechanism-based therapiesMeasures of efficacyFDA-approved CDK4/6 inhibitorsAge-matched controlsJanus kinase