2024
Oral decitabine–cedazuridine versus intravenous decitabine for myelodysplastic syndromes and chronic myelomonocytic leukaemia (ASCERTAIN): a registrational, randomised, crossover, pharmacokinetics, phase 3 study
Garcia-Manero G, McCloskey J, Griffiths E, Yee K, Zeidan A, Al-Kali A, Deeg H, Patel P, Sabloff M, Keating M, Zhu N, Gabrail N, Fazal S, Maly J, Odenike O, Kantarjian H, DeZern A, O'Connell C, Roboz G, Busque L, Buckstein R, Amin H, Randhawa J, Leber B, Shastri A, Dao K, Oganesian A, Hao Y, Keer H, Azab M, Savona M. Oral decitabine–cedazuridine versus intravenous decitabine for myelodysplastic syndromes and chronic myelomonocytic leukaemia (ASCERTAIN): a registrational, randomised, crossover, pharmacokinetics, phase 3 study. The Lancet Haematology 2024, 11: e15-e26. PMID: 38135371, DOI: 10.1016/s2352-3026(23)00338-1.Peer-Reviewed Original ResearchConceptsChronic myelomonocytic leukemiaIntravenous decitabineMyelodysplastic syndromeMyelomonocytic leukemiaOral therapyPrimary endpointAdverse eventsEastern Cooperative Oncology Group performance status 0Treatment cyclesCycle 1Full treatment dosePerformance status 0Treatment-related deathsFrequent adverse eventsSerious adverse eventsPhase 3 studyPhase 3 trialPotential treatment benefitsCommunity-based clinicsAcute myeloid leukemiaNext treatment cycleTreatment of individualsOral decitabineStatus 0Treatment discontinuation
2022
A randomized phase 2 trial of azacitidine with or without durvalumab as first-line therapy for higher-risk myelodysplastic syndromes
Zeidan AM, Boss I, Beach C, Copeland WB, Thompson E, Fox BA, Hasle VE, Ogasawara K, Cavenagh J, Silverman LR, Voso MT, Hellmann A, Tormo M, O'Connor T, Previtali A, Rose S, Garcia-Manero G. A randomized phase 2 trial of azacitidine with or without durvalumab as first-line therapy for higher-risk myelodysplastic syndromes. Blood Advances 2022, 6: 2207-2218. PMID: 34972214, PMCID: PMC9006291, DOI: 10.1182/bloodadvances.2021005487.Peer-Reviewed Original ResearchConceptsHigh-risk myelodysplastic syndromeAdverse eventsArm BArm ASubcutaneous azacitidineMyelodysplastic syndromeTreatment cyclesRandomized phase 2 trialInhibitory immune checkpoint moleculesHematologic adverse eventsMedian overall survivalFirst-line therapyFirst-line treatmentPhase 2 studyPhase 2 trialImmune checkpoint moleculesOverall response rateBone marrow granulocytesAzacitidine monotherapyIntravenous durvalumabCheckpoint moleculesOverall survivalClinical outcomesMarrow granulocytesGrade 3
2019
Efficacy and Safety of Azacitidine (AZA) in Combination with the Anti-PD-L1 Durvalumab (durva) for the Front-Line Treatment of Older Patients (pts) with Acute Myeloid Leukemia (AML) Who Are Unfit for Intensive Chemotherapy (IC) and Pts with Higher-Risk Myelodysplastic Syndromes (HR-MDS): Results from a Large, International, Randomized Phase 2 Study
Zeidan A, Cavenagh J, Voso M, Taussig D, Tormo M, Boss I, Copeland W, Gray V, Previtali A, O'Connor T, Rose S, Beach C, Silverman L. Efficacy and Safety of Azacitidine (AZA) in Combination with the Anti-PD-L1 Durvalumab (durva) for the Front-Line Treatment of Older Patients (pts) with Acute Myeloid Leukemia (AML) Who Are Unfit for Intensive Chemotherapy (IC) and Pts with Higher-Risk Myelodysplastic Syndromes (HR-MDS): Results from a Large, International, Randomized Phase 2 Study. Blood 2019, 134: 829. DOI: 10.1182/blood-2019-122896.Peer-Reviewed Original ResearchHigh-risk myelodysplastic syndromePD-L1 surface expressionAcute myeloid leukemiaPlatinum-containing chemotherapyPhase 2 studyIntensive chemotherapyArm AMyeloid blastsCelgene CorporationAML ptsMedian OSPD-L1AML cohortDisease progressionSurface expressionTreatment groupsTreatment cyclesECOG performance status 0First large randomized trialLarger phase 2 studiesPD-L1 blocking antibodiesRandomized phase 2 studyConcurrent platinum-based chemotherapyResponse criteriaSafety of azacitidine