Clinical Outcomes and Variability Based on Baseline Cytogenetic Risk of Patients with MDS Treated with Hypomethylating Agents: An Analysis from the International Consortium for MDS (icMDS) Validate Database
Getz T, Kewan T, Bewersdorf J, Stempel J, Lanino L, Wei W, Al Ali N, DeZern A, Sekeres M, Uy G, Carraway H, Desai P, Griffiths E, Stein E, Brunner A, McMahon C, Shallis R, Zeidner J, Savona M, Ball S, Chandhok N, Logothetis C, Bidikian A, Roboz G, Rolles B, Wang E, Harris A, Amaya M, Hawkins H, Grenet J, Xie Z, Madanat Y, Abaza Y, Badar T, Haferlach T, Maciejewski J, Sallman D, Enjeti A, Al-Rabi K, Halahleh K, Hiwase D, Diez-Campelo M, Valcarcel D, Haferlach C, Pleyer L, Kotsianidis I, Pappa V, Santini V, Consagra A, Al-Kali A, Ogawa S, Nannya Y, Stahl M, Della Porta M, Komrokji R, Zeidan A. Clinical Outcomes and Variability Based on Baseline Cytogenetic Risk of Patients with MDS Treated with Hypomethylating Agents: An Analysis from the International Consortium for MDS (icMDS) Validate Database. Blood 2024, 144: 3219-3219. DOI: 10.1182/blood-2024-202075.Peer-Reviewed Original ResearchNon-complex karyotypeInternational Prognostic Scoring SystemCytogenetic risk groupHMA initiationComplex karyotypeIPSS-RHypomethylating agentsOverall survivalRisk groupsCytogenetic abnormalitiesAllogeneic hematopoietic stem cell transplantationHematopoietic stem cell transplantationAssociated with worse survivalHypomethylating agent combinationsPoor-risk cytogeneticsPeripheral blood blastsTreated with azacitidinePrognostic Scoring SystemMeasured overall survivalStem cell transplantationKaplan-Meier methodLog-rank testOutcomes of PTTime-to-event analysisRisk of patientsOral Decitabine/Cedazuridine in Patients with MDS and TP53 Mutations: A Propensity Score Matching Analysis from the Phase II and III Trials
Urrutia S, Sasaki K, Bataller A, Kantarjian H, Montalban-Bravo G, McCloskey J, Griffiths E, Yee K, Zeidan A, Savona M, Oganesian A, Sano Y, Keer H, Garcia-Manero G. Oral Decitabine/Cedazuridine in Patients with MDS and TP53 Mutations: A Propensity Score Matching Analysis from the Phase II and III Trials. Blood 2024, 144: 661-661. DOI: 10.1182/blood-2024-193274.Peer-Reviewed Original ResearchMedian overall survivalHematopoietic stem cell transplantationHypomethylating agentsTP53 mutationsOverall survivalImproved survivalMedian follow-up timeIPSS-R scoreComplete response rateStem cell transplantationECOG performance statusPropensity score matching analysisFollow-up timeScore matching analysisIPSS-RComplex cytogeneticsCell transplantationPerformance statusDecitabine/cedazuridineTP53wtCo-mutationsLandmark analysisPoor outcomeTP53mutMedian numberEvaluating Molecular and Clinical Predictors in Myelodysplastic Syndromes through Machine Learning Integration
Mosquera Orgueira A, Perez Encinas M, Pérez Míguez C, Crucitti D, Piñeiro Fiel M, Díaz Varela N, Mora E, Díaz-Beyá M, Montoro M, Pomares H, Ramos Ortega F, Tormo M, Jerez A, Nomdedeu J, de Miguel Sanchez C, Arenillas L, Carcel Corella P, Cedena Romero M, Xicoy B, Rivero M, Del Orbe Barreto R, Bewersdorf J, Stahl M, Stempel J, Kewan T, Zeidan A, Diez-Campelo M, Valcarcel D. Evaluating Molecular and Clinical Predictors in Myelodysplastic Syndromes through Machine Learning Integration. Blood 2024, 144: 6683-6683. DOI: 10.1182/blood-2024-198114.Peer-Reviewed Original ResearchLeukemia-free survivalPredictors of OSMyelodysplastic syndromeOverall survivalIPSS-MC-indexFLT3-ITDPredictors of leukemia-free survivalRevised International Prognostic Scoring SystemPrognostication of myelodysplastic syndromesInternational Prognostic Scoring SystemPrognostic Scoring SystemCox regression analysisMolecular dataClinical trial designIPSS-RGenetic variabilityMLL-PTDRandom survival forestPrognostic landscapePrognostic significanceLaboratory parametersAffected prognosisClinical predictorsClinical indicesTrial in Progress: A Randomized, Double-Blind, Placebo-Controlled, Multicenter Phase 2 Study of AK117/Placebo in Combination with Azacitidine in Patients with Newly Diagnosed Higher-Risk Myelodysplastic Syndromes (AK117-205)
Zeidan A, Tong H, Xiao Z, Baratam P, Abboud R, Benton C, Zeidner J, Borate U, Chai-Ho W, Lu Y, Yang J, Hu M, Li B, Xia M, Sallman D. Trial in Progress: A Randomized, Double-Blind, Placebo-Controlled, Multicenter Phase 2 Study of AK117/Placebo in Combination with Azacitidine in Patients with Newly Diagnosed Higher-Risk Myelodysplastic Syndromes (AK117-205). Blood 2024, 144: 6705-6705. DOI: 10.1182/blood-2024-200541.Peer-Reviewed Original ResearchAllogeneic hematopoietic stem cell transplantationHematopoietic stem cell transplantationEastern Cooperative Oncology GroupIPSS-R scoreEvent-free survivalStem cell transplantationAcute myeloid leukemiaOverall survivalIPSS-RTransfusion independenceComplete responseCR rateDouble-blindCell transplantationHR-MDSMyeloproliferative neoplasmsAdverse eventsChimeric antigen receptor T cellsTransformation to acute myeloid leukemiaAnemia ratesMulticenter phase 2 studyTreated with hypomethylating agentsHigher-risk myelodysplastic syndromesSeverity of adverse eventsAdequate organ functionA Phase 2B, Open-Label Multicenter Study of Tebapivat (AG-946), a Potent Pyruvate Kinase Activator, in Patients with Anemia Due to Lower-Risk Myelodysplastic Syndromes
Zeidan A, Sekeres M, Al-Samkari H, Carraway H, DeZern A, Mittelman M, Little M, Beynon V, Dai X, Sommakia S, Despotovic J, Patel P, Dibacco M, Fattizzo B, Stein E, Sallman D, Kulasekararaj A, Platzbecker U, Fenaux P. A Phase 2B, Open-Label Multicenter Study of Tebapivat (AG-946), a Potent Pyruvate Kinase Activator, in Patients with Anemia Due to Lower-Risk Myelodysplastic Syndromes. Blood 2024, 144: 6708-6708. DOI: 10.1182/blood-2024-203073.Peer-Reviewed Original ResearchLower-risk MDSErythropoiesis-stimulating agentsLower-risk myelodysplastic syndromesRed blood cell unitsMyelodysplastic syndromeProportion of patientsDose levelsRed blood cellsIPSS-RTransfusion burdenOpen-labelFirst doseRevised International Prognostic Scoring SystemHistory of acute myeloid leukemiaMDS mouse modelsMedian duration of responsePhase 2bInternational Prognostic Scoring SystemOpen-label multicenter studyAssociated with increased morbidityBone marrow neoplasmsHigh transfusion burdenIPSS-R scoreLow transfusion burdenDose level 1Clinical and Genomic-Based Decision Support System to Define the Optimal Timing of Allogeneic Hematopoietic Stem-Cell Transplantation in Patients With Myelodysplastic Syndromes
Tentori C, Gregorio C, Robin M, Gagelmann N, Gurnari C, Ball S, Caballero Berrocal J, Lanino L, D'Amico S, Spreafico M, Maggioni G, Travaglino E, Sauta E, Meggendorfer M, Zhao L, Campagna A, Savevski V, Santoro A, Al Ali N, Sallman D, Sole F, Garcia-Manero G, Germing U, Kroger N, Kordasti S, Santini V, Sanz G, Kern W, Platzbecker U, Diez-Campelo M, Maciejewski J, Ades L, Fenaux P, Haferlach T, Zeidan A, Castellani G, Komrokji R, Ieva F, Della Porta M, Bernardi M, Di Grazia C, Vago L, Rivoli G, Borin L, Chiusolo P, Giaccone L, Voso M, Bewersdorf J, Nibourel O, Beyá M, Jerez A, Hernández F, Kennedy K, Xicoy B, Ubezio M, Russo A, Todisco G, Mannina D, Bramanti S, Zampini M, Riva E, Bicchieri M, Asti G, Viviani F, Buizza A, Tinterri B, Kubasch A, Bacigalupo A, Raiola A, Rambaldi A, Passamonti F, Ciceri F. Clinical and Genomic-Based Decision Support System to Define the Optimal Timing of Allogeneic Hematopoietic Stem-Cell Transplantation in Patients With Myelodysplastic Syndromes. Journal Of Clinical Oncology 2024, 42: 2873-2886. PMID: 38723212, PMCID: PMC11328926, DOI: 10.1200/jco.23.02175.Peer-Reviewed Original ResearchHematopoietic stem-cell transplantationAllogeneic hematopoietic stem-cell transplantationStem-cell transplantationMyelodysplastic syndromeIPSS-MMolecular International Prognostic Scoring SystemInternational Prognostic Scoring SystemPrognostic Scoring SystemTime of transplantationProportion of patientsHigh-risk categoryOptimal timingProlonged life expectancyRevised IPSSIPSS-RRetrospective populationValidation cohortCurative treatmentClinical relevanceTransplantationPatientsModerately high-Scoring systemAverage survivalLife expectancy