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
2023
STIMULUS-MDS2 design and rationale: a phase III trial with the anti-TIM-3 sabatolimab (MBG453) + azacitidine in higher risk MDS and CMML-2
Zeidan A, Giagounidis A, Sekeres M, Xiao Z, Sanz G, Van Hoef M, Ma F, Hertle S, Santini V. STIMULUS-MDS2 design and rationale: a phase III trial with the anti-TIM-3 sabatolimab (MBG453) + azacitidine in higher risk MDS and CMML-2. Future Oncology 2023, 19: 631-642. PMID: 37083373, DOI: 10.2217/fon-2022-1237.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsHigh-risk myelodysplastic syndromeChronic myelomonocytic leukemiaMyelodysplastic syndromeCMML-2Tim-3Hematopoietic stem cell transplantationT-cell immunoglobulin domainMucin domain 3Risk myelodysplastic syndromesPhase III trialsStem cell transplantationLeukemic stem cellsFavorable tolerabilityIII trialsNovel immunotherapiesPoor outcomeCell transplantationLeukemic blastsClinical trialsNovel therapiesMyelomonocytic leukemiaDurable benefitImmune systemMyeloid malignanciesMeaningful improvements
2022
A phase 1b study of glasdegib + azacitidine in patients with untreated acute myeloid leukemia and higher-risk myelodysplastic syndromes
Sekeres MA, Schuster M, Joris M, Krauter J, Maertens J, Breems D, Gyan E, Kovacsovics T, Verma A, Vyas P, Wang ES, Ching K, O’Brien T, Gallo Stampino C, Ma WW, Kudla A, Chan G, Zeidan AM. A phase 1b study of glasdegib + azacitidine in patients with untreated acute myeloid leukemia and higher-risk myelodysplastic syndromes. Annals Of Hematology 2022, 101: 1689-1701. PMID: 35488900, DOI: 10.1007/s00277-022-04853-4.Peer-Reviewed Original ResearchConceptsAcute myeloid leukemiaHigh-risk myelodysplastic syndromePhase 1b studyChronic myelomonocytic leukemiaMyelodysplastic syndromeExpansion cohortSafety profileMDS cohortMyeloid leukemiaTreatment-emergent adverse eventsUntreated acute myeloid leukemiaNon-hematologic gradeMedian overall survivalAcceptable safety profileOverall response rateDrug-drug interactionsSafety cohortIntensive chemotherapyAdverse eventsOverall survivalClinical benefitQT prolongationAML cohortMyelomonocytic leukemiaGlasdegib
2020
AML-207: Glasdegib in Combination with Azacitidine in Patients with Untreated Higher-Risk Myelodysplastic Syndromes, Acute Myeloid Leukemia, and Chronic Myelomonocytic Leukemia: Effects on Marrow Recovery and Transfusion Independence
Zeidan A, Schuster M, Joris M, Krauter J, Maertens J, Gyan E, Kovacsovics T, Verma A, Vyas P, Wang E, Ma W, Zeremski M, Kudla A, Chan G, Sekeres M. AML-207: Glasdegib in Combination with Azacitidine in Patients with Untreated Higher-Risk Myelodysplastic Syndromes, Acute Myeloid Leukemia, and Chronic Myelomonocytic Leukemia: Effects on Marrow Recovery and Transfusion Independence. Clinical Lymphoma Myeloma & Leukemia 2020, 20: s191-s192. DOI: 10.1016/s2152-2650(20)30733-3.Peer-Reviewed Original ResearchHigh-risk myelodysplastic syndromeAbsolute neutrophil countChronic myelomonocytic leukemiaAcute myeloid leukemiaMyelodysplastic syndromeEvaluable patientsIntensive chemotherapyMedian durationTransfusion independenceMarrow recoveryHematopoietic recoveryMyeloid leukemiaMyelomonocytic leukemiaEarly marrow recoveryEarly platelet recoveryUp-front treatmentManageable safety profileOpen-label studyRate of transfusionMain outcome measuresEarly hematopoietic recoveryCycle 1Cycle 2Dose delaysPartial remissionHealth-related quality of life (HRQoL) in patients with untreated higher-risk myelodysplastic syndromes (MDS), acute myeloid leukemia (AML), and chronic myelomonocytic leukemia (CMML) receiving glasdegib + azacitidine (AZA).
Wang E, Bell T, Zeidan A, Bhattacharyya H, Kudla A, Chan G, Sekeres M. Health-related quality of life (HRQoL) in patients with untreated higher-risk myelodysplastic syndromes (MDS), acute myeloid leukemia (AML), and chronic myelomonocytic leukemia (CMML) receiving glasdegib + azacitidine (AZA). Journal Of Clinical Oncology 2020, 38: 7527-7527. DOI: 10.1200/jco.2020.38.15_suppl.7527.Peer-Reviewed Original ResearchChronic myelomonocytic leukemiaAcute myeloid leukemiaMyelodysplastic syndromeIntensive chemotherapyGlobal ImpressionAML cohortAML/myelodysplastic syndromeHigh-risk myelodysplastic syndromeMD Anderson Symptom InventoryFirst-line treatment optionLower symptom burdenPhase Ib studyEnd of treatmentQuality of lifeStudy medicationRemission rateOverall survivalSymptom burdenMDS cohortTreatment optionsMyeloid leukemiaMedian numberMyelomonocytic leukemiaGlasdegibAzacitidine
2019
A Phase 1b Study of Glasdegib in Combination with Azacitidine in Patients with Untreated Higher-Risk Myelodysplastic Syndromes, Acute Myeloid Leukemia, and Chronic Myelomonocytic Leukemia
Sekeres M, Schuster M, Joris M, Krauter J, Maertens J, Gyan E, Kovacsovics T, Verma A, Vyas P, Wang E, Wendy W, Zeremski M, Kudla A, Chan G, Zeidan A. A Phase 1b Study of Glasdegib in Combination with Azacitidine in Patients with Untreated Higher-Risk Myelodysplastic Syndromes, Acute Myeloid Leukemia, and Chronic Myelomonocytic Leukemia. Blood 2019, 134: 177. DOI: 10.1182/blood-2019-124050.Peer-Reviewed Original ResearchHigh-risk myelodysplastic syndromeChronic myelomonocytic leukemiaAcute myeloid leukemiaLow-dose cytarabineMedian treatment durationComplete remissionPhase 1b trialIntensive chemotherapyOverall survivalMyelodysplastic syndromePersonal feesAdverse eventsMyelomonocytic leukemiaSpeakers bureauSerious TEAEsFebrile neutropeniaMedian ageMedian timeEuropean LeukemiaNetRisk categoriesMyeloid leukemiaMedian (95% CI) OSMortality rateTreatment durationCR/complete remission
2017
Hypomethylating agent therapy use and survival in older patients with chronic myelomonocytic leukemia in the United States: A large population‐based study
Zeidan AM, Hu X, Long JB, Wang R, Ma X, Podoltsev NA, Huntington SF, Gore SD, Davidoff AJ. Hypomethylating agent therapy use and survival in older patients with chronic myelomonocytic leukemia in the United States: A large population‐based study. Cancer 2017, 123: 3754-3762. PMID: 28621841, PMCID: PMC6540984, DOI: 10.1002/cncr.30814.Peer-Reviewed Original ResearchConceptsChronic myelomonocytic leukemiaRisk of deathSupportive careEnd Results-Medicare databaseOlder adultsMedian OS timeOverall survival benefitCohort of patientsProportional hazards modelUse of HMAsMedian OSAgent therapySurvival benefitOS timeCMML patientsMyelomonocytic leukemiaHazards modelHMA treatmentPatientsTemporal improvementSecondary analysisPropensity scoreLimited evidenceSurvival changesApproval32 Hypomethylating Agent Therapy use and Survival in Older Patients with Chronic Myelomonocytic Leukemia in USA: A Large Population-Based Study
Zeidan A, Hu X, Long J, Wang R, Ma X, Podoltsev N, Huntington S, Gore S, Davidoff A. 32 Hypomethylating Agent Therapy use and Survival in Older Patients with Chronic Myelomonocytic Leukemia in USA: A Large Population-Based Study. Leukemia Research 2017, 55: s20-s21. DOI: 10.1016/s0145-2126(17)30145-5.Peer-Reviewed Original ResearchChronic myelomonocytic leukemiaOlder patientsTherapy useMyelomonocytic leukemiaLarge populationPatientsLeukemia
2016
Hypomethylating Agent Therapy and Survival Among Older Patients with Chronic Myelomonocytic Leukemia in the United States: A Large Population-Based Study
Zeidan A, Hu X, Long J, Wang R, Huntington S, Podoltsev N, Gore S, Ma X, Davidoff A. Hypomethylating Agent Therapy and Survival Among Older Patients with Chronic Myelomonocytic Leukemia in the United States: A Large Population-Based Study. Blood 2016, 128: 394. DOI: 10.1182/blood.v128.22.394.394.Peer-Reviewed Original ResearchChronic myelomonocytic leukemiaMyelodysplastic syndromeSurvival benefitHigh-risk myelodysplastic syndromeDemonstrated survival benefitRetrospective cohort studyRisk myelodysplastic syndromesUse of HMAsAgent azacitidineLack of evidenceCohort studyClinical entityMyelomonocytic leukemiaBiologic evidenceOlder adultsAzacitidineUnited StatesHMAsEnd resultPatientsSyndromeLeukemiaDecitabineEpidemiology