2023
Considerations 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
MDS-476 Sabatolimab (MBG453) Combination Treatment Regimens for Patients With Higher-Risk Myelodysplastic Syndromes (HR-MDS): The Myelodysplastic Syndromes Studies in the STIMULUS Immuno-Myeloid Clinical Trial Program
Zeidan A, Al-Kali A, Borate U, Cluzeau T, DeZern A, Esteve J, Giagounidis A, Kobata K, Lyons R, Platzbecker U, Sallman D, Santini V, Sanz G, Sekeres M, Wei A, Xiao Z, Van Hoef M, Nourry-Boulot C, Sadek I, Ma F, Iordan A, Sabo J, Garcia-Manero G. MDS-476 Sabatolimab (MBG453) Combination Treatment Regimens for Patients With Higher-Risk Myelodysplastic Syndromes (HR-MDS): The Myelodysplastic Syndromes Studies in the STIMULUS Immuno-Myeloid Clinical Trial Program. Clinical Lymphoma Myeloma & Leukemia 2022, 22: s317. DOI: 10.1016/s2152-2650(22)01420-3.Peer-Reviewed Original ResearchHematopoietic stem cell transplantLeukemia-free survivalPhase II trialHigh-risk myelodysplastic syndromeHR-MDS patientsClinical trial programII trialLeukemic stem cellsCombination therapyTim-3Trial programLeukemic cellsTransfusion-free intervalEvent-free survivalPhase III trialsStem cell transplantOverall response rateEarly phase trialsNovartis Pharmaceuticals CorporationImprovement of fatigueExpansion cohortIntensive chemotherapyPrimary endpointDurable responsesIII trialsAML-484 First Results of a Phase II Study (STIMULUS-AML1) Investigating Sabatolimab + Azacitidine + Venetoclax in Patients With Newly Diagnosed Acute Myeloid Leukemia (ND AML)
Zeidan A, Westermann J, Kovacsovics T, Assouline S, Schuh A, Kim H, Macias G, Sanford D, Luskin M, Stein E, Malek K, Lyu J, Stegert M, Esteve J. AML-484 First Results of a Phase II Study (STIMULUS-AML1) Investigating Sabatolimab + Azacitidine + Venetoclax in Patients With Newly Diagnosed Acute Myeloid Leukemia (ND AML). Clinical Lymphoma Myeloma & Leukemia 2022, 22: s255. DOI: 10.1016/s2152-2650(22)01303-9.Peer-Reviewed Original ResearchTreatment-related AEsDose-escalation partDose-limiting toxicityIntensive chemotherapyDosage reductionCohort 2Acute myeloid leukemiaDose interruptionFebrile neutropeniaSerious AEsExpansion cohortStudy patientsTreatment discontinuationAdult patientsDurable responsesNeutrophil countTim-3Agent therapyMyelodysplastic syndromePlatelet countSafety profilePatient outcomesMyeloid leukemiaPatientsDay 1Immune Checkpoint Inhibition in Acute Myeloid Leukemia and Myelodysplastic Syndromes
Abaza Y, Zeidan AM. Immune Checkpoint Inhibition in Acute Myeloid Leukemia and Myelodysplastic Syndromes. Cells 2022, 11: 2249. PMID: 35883692, PMCID: PMC9318025, DOI: 10.3390/cells11142249.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsAcute myeloid leukemiaImmune checkpoint inhibitorsHigh-risk myelodysplastic syndromeImmune checkpoint inhibitionMyelodysplastic syndromeCheckpoint inhibitionMyeloid leukemiaInnate immune checkpointPD-1 inhibitorsEarly clinical trialsEarly phase trialsLow mutational burdenCheckpoint inhibitorsDurable responsesImmune checkpointsRandomized trialsCTLA-4Clinical trialsImmune escapePhase trialsMutational burdenSolid tumorsMyeloid malignanciesTrialsLack of activityLong-term utilization and benefit of luspatercept in patients (pts) with lower-risk myelodysplastic syndromes (LR-MDS) from the MEDALIST trial.
Fenaux P, Santini V, Komrokji R, Zeidan A, Garcia-Manero G, Buckstein R, Miteva D, Keeperman K, Holot N, Zhang J, Hughes C, Rosettani B, Yucel A, Platzbecker U. Long-term utilization and benefit of luspatercept in patients (pts) with lower-risk myelodysplastic syndromes (LR-MDS) from the MEDALIST trial. Journal Of Clinical Oncology 2022, 40: 7056-7056. DOI: 10.1200/jco.2022.40.16_suppl.7056.Peer-Reviewed Original ResearchLower-risk myelodysplastic syndromesAcute myeloid leukemiaErythropoiesis-stimulating agentsMedian cumulative durationCumulative durationRBC-TIMedian durationPlacebo armAML progressionRegular red blood cell transfusionsRed blood cell transfusionRBC transfusion independenceBlood cell transfusionHigh-risk MDSKaplan-Meier analysisLong-term followRate of progressionLong-term clinical valueEligible ptsCell transfusionPrimary endpointDurable responsesTransfusion independenceAML diagnosisDose escalation
2013
HLA-Haploidentical Donor Lymphocyte Infusions for Patients with Relapsed Hematologic Malignancies after Related HLA-Haploidentical Bone Marrow Transplantation
Zeidan AM, Forde PM, Symons H, Chen A, Smith BD, Pratz K, Carraway H, Gladstone DE, Fuchs EJ, Luznik L, Jones RJ, Bolaños-Meade J. HLA-Haploidentical Donor Lymphocyte Infusions for Patients with Relapsed Hematologic Malignancies after Related HLA-Haploidentical Bone Marrow Transplantation. Transplantation And Cellular Therapy 2013, 20: 314-318. PMID: 24296490, PMCID: PMC4010132, DOI: 10.1016/j.bbmt.2013.11.020.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAdultAgedAntineoplastic Agents, AlkylatingBone Marrow TransplantationChildChild, PreschoolCyclophosphamideFemaleGraft vs Host DiseaseHaplotypesHLA AntigensHumansLeukemia, Myeloid, AcuteLymphocyte TransfusionLymphomaMaleMiddle AgedRecurrenceRemission InductionSurvival AnalysisT-LymphocytesTransplantation ConditioningTransplantation, IsogeneicConceptsPost-transplantation cyclophosphamideDonor lymphocyte infusionBone marrow transplantationComplete responseLymphocyte infusionMarrow transplantationT-cell-replete bone marrow transplantationHLA-haploidentical bone marrow transplantationRelapsed hematologic malignanciesTreatment of relapseCells/Acute myeloid leukemiaAcute GVHDChronic GVHDAcceptable toxicityHost diseaseDurable responsesMedian durationMedian ageNonmyeloablative conditioningMedian timeEntire cohortHematologic malignanciesMyeloid leukemiaGrade 3