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 efficacyConsensus 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