2023
Validation of the Molecular International Prognostic Scoring System (IPSS-M) in Patients (Pts) with Myelodysplastic Syndromes/Neoplasms (MDS) Who Were Treated with Hypomethylating Agents (HMA)
Kewan T, Bewersdorf J, Blaha O, Stahl M, Al Ali N, DeZern A, Sekeres M, Carraway H, Desai P, Griffiths E, Stein E, Brunner A, Amaya M, Zeidner J, Savona M, Stempel J, Chandhok N, Logothetis C, Ramaswamy R, Rose A, Roboz G, Rolles B, Wang E, Harris A, Shallis R, Xie Z, Padron E, Maciejewski J, Sallman D, Della Porta M, Komrokji R, Zeidan A. Validation of the Molecular International Prognostic Scoring System (IPSS-M) in Patients (Pts) with Myelodysplastic Syndromes/Neoplasms (MDS) Who Were Treated with Hypomethylating Agents (HMA). Blood 2023, 142: 3240. DOI: 10.1182/blood-2023-186340.Peer-Reviewed Original ResearchComplete remission rateOverall response rateOutcome of ptsMedian overall survivalOverall survivalHypomethylating agentHMA initiationHR-MDSC-indexRisk groupsScoring systemInternational Prognostic Scoring SystemResponse criteriaPrognostic scoring systemHigh-risk diseaseLarge multicenter cohortHigh-risk groupHarrell's C-indexLog-rank testPrediction of outcomeDifferent scoring systemsSubsequent validation studiesHMA cyclesMedian followAllogeneic HSCTPost Allogeneic Stem Cell Transplant Outcomes Following Response to Hypomethylating Agent Therapy in Myelodysplastic Syndromes Are Predicted By Persistent International Prognostic Scoring System-Molecular Risk
Frumm S, Kim H, Kelkar A, Ho V, Gooptu M, Gibson C, Koreth J, Shapiro R, Romee R, Nikiforow S, Antin J, Soiffer R, Rolles B, Shimony S, Bewersdorf J, Kewan T, Alhajahjeh A, Luskin M, Garcia J, Chen E, Lane A, Wadleigh M, Winer E, Stone R, DeAngelo D, Zeidan A, Lindsley C, Cutler C, Stahl M. Post Allogeneic Stem Cell Transplant Outcomes Following Response to Hypomethylating Agent Therapy in Myelodysplastic Syndromes Are Predicted By Persistent International Prognostic Scoring System-Molecular Risk. Blood 2023, 142: 3618. DOI: 10.1182/blood-2023-185220.Peer-Reviewed Original ResearchHematopoietic stem cell transplantBlood count recoveryPost-HCT outcomesComplete remissionTime of diagnosisMyelodysplastic syndromeOverall survivalHigh riskLower riskAgent therapyCount recoveryMolecular riskInternational Working Group response criteriaShorter median overall survivalResponse criteriaDana-Farber Cancer InstituteHCT comorbidity indexImportant prognostic impactTAC/sirolimusHost disease (GVHD) prophylaxisMedian overall survivalProgression-free survivalStem cell transplantBone marrow biopsyFuture prospective studiesClassification, risk stratification and response assessment in myelodysplastic syndromes/neoplasms (MDS): A state-of-the-art report on behalf of the International Consortium for MDS (icMDS)
Stahl M, Bewersdorf J, Xie Z, Porta M, Komrokji R, Xu M, Abdel-Wahab O, Taylor J, Steensma D, Starczynowski D, Sekeres M, Sanz G, Sallman D, Roboz G, Platzbecker U, Patnaik M, Padron E, Odenike O, Nimer S, Nazha A, Majeti R, Loghavi S, Little R, List A, Kim T, Hourigan C, Hasserjian R, Halene S, Griffiths E, Gore S, Greenberg P, Figueroa M, Fenaux P, Efficace F, DeZern A, Daver N, Churpek J, Carraway H, Buckstein R, Brunner A, Boultwood J, Borate U, Bejar R, Bennett J, Wei A, Santini V, Savona M, Zeidan A. Classification, risk stratification and response assessment in myelodysplastic syndromes/neoplasms (MDS): A state-of-the-art report on behalf of the International Consortium for MDS (icMDS). Blood Reviews 2023, 62: 101128. PMID: 37704469, DOI: 10.1016/j.blre.2023.101128.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsInternational consensus classificationResponse assessmentWorld Health Organization classificationPatient-centered careRisk assessment toolClinical outcomesRisk stratificationOrganization classificationCentered careTherapeutic benefitTherapeutic outcomesConsensus classificationResponse criteriaInternational ConsortiumNeoplasmsLife assessmentAssessment toolOutcomesReportAssessmentPrognosticationCareEvolution of Therapeutic Benefit Measurement Criteria in Myelodysplastic Syndromes/Neoplasms
Stempel J, Xie Z, Bewersdorf J, Stahl M, Zeidan A. Evolution of Therapeutic Benefit Measurement Criteria in Myelodysplastic Syndromes/Neoplasms. The Cancer Journal 2023, 29: 203-211. PMID: 37195777, DOI: 10.1097/ppo.0000000000000666.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsInternational Working Group response criteriaResponse criteriaPhase III clinical trialsIWG 2006 criteriaRisk of progressionPatient-focused outcomesClonal myeloid neoplasmsAcute myeloid leukemiaTherapeutic response assessmentPatient-centered responsesNovel drug developmentHematologic recoveryProgressive cytopeniasClinical trialsIWG criteriaLong-term benefitsMyeloid leukemiaIneffective hematopoiesisMyeloid neoplasmsResponse assessmentDisease severityConsensus 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 agentsConsiderations for Drug Development in Myelodysplastic Syndromes
Sekeres M, Kim N, DeZern A, Norsworthy K, Garcia J, de Claro R, Theoret M, Jen E, Ehrlich L, Zeidan A, Komrokji R. Considerations for Drug Development in Myelodysplastic Syndromes. Clinical Cancer Research 2023, 29: 2573-2579. PMID: 36688922, PMCID: PMC10349686, DOI: 10.1158/1078-0432.ccr-22-3348.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsMyelodysplastic syndromeTrial designDrug developmentResponse criteriaLow-risk diseaseHigh-risk patientsFuture trial designClinical trial designQuality of lifeValidation of PatientHigh-need populationDurable responsesOverall survivalAnemic patientsTransfusion dependencyClinical benefitPatient populationAdvanced ageClinical trialsDose reductionOutcome instrumentsNew therapiesPreclinical modelingPatientsActive drug
2022
International Working Group (IWG) Response Criteria and Association with Overall Survival in Patients with Myelodysplastic Syndromes Treated with Hypomethylating Agents - a Systematic Review and Meta-Analysis
Bewersdorf J, Grimshaw A, Platzbecker U, Fenaux P, Sekeres M, Zeidan A, Stahl M. International Working Group (IWG) Response Criteria and Association with Overall Survival in Patients with Myelodysplastic Syndromes Treated with Hypomethylating Agents - a Systematic Review and Meta-Analysis. Blood 2022, 140: 9811-9812. DOI: 10.1182/blood-2022-158622.Peer-Reviewed Original ResearchEvaluating complete remission with partial hematologic recovery (CRh) as a response criterion in myelodysplastic syndromes (MDS)
Brunner A, Gavralidis A, Ali N, Hunter A, Komrokji R, Zeidan A, Sallman D. Evaluating complete remission with partial hematologic recovery (CRh) as a response criterion in myelodysplastic syndromes (MDS). Blood Cancer Journal 2022, 12: 153. PMID: 36379923, PMCID: PMC9666661, DOI: 10.1038/s41408-022-00748-9.Peer-Reviewed Original ResearchConceptsPartial hematologic recoveryMyelodysplastic syndromeHematologic recoveryResponse criteriaCR/CRhIWG 2006 criteriaDuration of therapyBest overall responseTime of therapyCR responseCRH responseDNMTi therapyOS associationComplete remissionMedian OSOverall survivalAdult patientsAllogeneic transplantsMedian ageMDS patientsMultivariable analysisClinical trialsSimilar survivalPatientsTherapy
2021
Evaluating Complete Remission with Incomplete Hematologic Recovery (CRh) As a Response Criterion in Myelodysplastic Syndromes (MDS)
Brunner A, Gavralidis A, Al Ali N, Komrokji R, Zeidan A, Sallman D. Evaluating Complete Remission with Incomplete Hematologic Recovery (CRh) As a Response Criterion in Myelodysplastic Syndromes (MDS). Blood 2021, 138: 1522. DOI: 10.1182/blood-2021-151815.Peer-Reviewed Original ResearchClinical Trials CommitteeStable diseaseComplete remissionHMA therapyBone marrow blastsHematologic improvementProgressive diseaseMyelodysplastic syndromePartial remissionTrials CommitteeResponse criteriaMarrow blastsOverall survivalSpeakers bureauHigh-risk myelodysplastic syndromeAdvisory CommitteeIncomplete hematologic recoveryIWG 2006 criteriaMethod of KaplanRisk myelodysplastic syndromesOngoing prospective studyMoffitt Cancer CenterBest overall responsePrediction of OSMassachusetts General Hospital
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