0000000000377173

AUTHOR

Abderrahmane Laadem

showing 6 related works from this author

Luspatercept Increases Hemoglobin and Reduces Transfusion Burden in Patients with Low-Intermediate Risk Myelodysplastic Syndromes (MDS): Long-Term Re…

2016

Abstract Background: Management of anemia is a common therapeutic challenge in patients with MDS. Luspatercept (ACE-536), a fusion protein containing modified activin receptor type IIB, is being developed for treatment of anemia in lower-risk MDS. Luspatercept binds GDF11 and other TGF-β superfamily ligands to promote late-stage erythroid differentiation and increase hemoglobin (Hgb) levels (Suragani R, Nat Med, 2014 and Attie K, Am J Hematol, 2014). Aims: This is an ongoing, phase 2, multicenter, open-label, long-term extension study to evaluate the effects of luspatercept in patients (pts) with low-intermediate risk MDS. Endpoints include long-term safety and tolerability, erythroid respo…

medicine.medical_specialtybusiness.industryAnemiaSurrogate endpointMyelodysplastic syndromesImmunologyPhases of clinical researchCell BiologyHematologymedicine.diseaseBiochemistryGastroenterologySurgery03 medical and health sciences0302 clinical medicineTolerability030220 oncology & carcinogenesisPharmacodynamicsInternal medicineMedicinebusinessAdverse effect030215 immunologyLenalidomidemedicine.drugBlood
researchProduct

Luspatercept Response in ESA-NaïVe/RS+ Patients and RS- Patients with Low-Intermediate Risk Myelodysplastic Syndromes (MDS)

2016

Abstract Background: Management of anemia is a common therapeutic challenge in patients with myelodysplastic syndromes (MDS). Luspatercept (ACE-536), a fusion protein containing modified activin receptor type IIB, is being developed for treatment of anemia in lower-risk MDS. Luspatercept binds GDF11 and other TGF-β superfamily ligands to promote late-stage erythroid differentiation and increase hemoglobin (Hgb) levels (Suragani R, Nat Med, 2014 and Attie K, Am J Hematol, 2014). Aims: This is an ongoing, phase 2, multicenter, open-label study to evaluate the effects of luspatercept in patient (pts) with low-intermediate risk MDS. Endpoints included erythroid response (IWG HI-E), RBC transfus…

medicine.medical_specialtyPediatricsbusiness.industryAnemiaMyelodysplastic syndromesImmunologyPhases of clinical researchCell BiologyHematologymedicine.diseaseBiochemistryGastroenterologyhemic and lymphatic diseasesPharmacodynamicsInternal medicineLuspaterceptCohortmedicineIntermediate riskbusinessLenalidomidemedicine.drugBlood
researchProduct

Biomarkers of Ineffective Erythropoiesis Predict Response to Luspatercept in Patients with Low or Intermediate-1 Risk Myelodysplastic Syndromes (MDS)…

2015

Abstract Background: Luspatercept is a fusion protein (modified activin receptor IIB-IgG Fc) being investigated for the treatment of anemias with ineffective erythropoiesis. MDS patients have increased Smad2/3 signaling in the bone marrow, leading to ineffective erythropoiesis. Luspatercept inhibits Smad2/3 signaling and promotes late-stage erythroid differentiation, thereby correcting ineffective erythropoiesis. Aims: This completed, 3-month, phase 2, multicenter, open-label study evaluated the effects of luspatercept on anemia in patients with low/int-1 risk MDS (IPSS classification). Study outcomes include erythroid response of increased hemoglobin (Hb) in low transfusion burden (LTB) pa…

Ineffective erythropoiesisOncologymedicine.medical_specialtyAnemiaImmunologyPopulationGene mutationmedicine.disease_causeLower riskBiochemistry03 medical and health sciences0302 clinical medicineInternal medicineMedicineeducationLenalidomideeducation.field_of_studybusiness.industryMyelodysplastic syndromesCell BiologyHematologymedicine.disease3. Good healthSurgery030220 oncology & carcinogenesisAbsolute neutrophil countbusiness030215 immunologymedicine.drugBlood
researchProduct

MDS-191: Long-Term Efficacy and Safety of Luspatercept in Lower-Risk Myelodysplastic Syndromes (MDS): Phase 2 PACE-MDS Study

2020

Background: Luspatercept, a first-in-class erythroid maturation agent, has been investigated in patients with LR-MDS and ring sideroblasts (RS) (MEDALIST; Fenaux and Platzbecker NEJM 2020) and in an ongoing Phase 3 trial regardless of RS status (COMMANDS, NCT03682536 ). The previously reported Phase 2 trial of luspatercept (Platzbecker Lanc Onc 2017) includes subtypes of LR-MDS with and without RS, regardless of prior ESA exposure, and various EPO levels. Aims: Evaluate the long-term safety and efficacy of luspatercept in LR-MDS. Methods: Patients were IPSS low/int-1, age ≥ 18 years, Hgb NCT01749514 ; NCT02268383 ). Results: As of 13July2019, 115 patients were enrolled, of whom 108 were tre…

myalgiaCancer Researchmedicine.medical_specialtyErythemabusiness.industryMyelodysplastic syndromesPeripheral edemaPhases of clinical researchHematologymedicine.diseaseLower riskClinical trialOncologyhemic and lymphatic diseasesInternal medicinemedicinemedicine.symptomBone painbusinessClinical Lymphoma Myeloma and Leukemia
researchProduct

Erythropoietic cellular analyses in luspatercept-treated lower-risk myelodysplastic syndromes (MDS): Phase 2 PACE-MDS study.

2018

7018Background: Luspatercept (ACE-536) is a TGF-β family ligand trap promoting late-stage erythroid (E) differentiation and increases in hemoglobin. Endpoints of the ongoing, phase 2, open-label st...

Cancer ResearchOncologybusiness.industryPhase (matter)Myelodysplastic syndromesLuspaterceptCancer researchMedicineHemoglobinbusinessLigand (biochemistry)medicine.diseaseLower riskJournal of Clinical Oncology
researchProduct

Luspatercept for the treatment of anaemia in patients with lower-risk myelodysplastic syndromes (PACE-MDS): a multicentre, open-label phase 2 dose-fi…

2017

Myelodysplastic syndromes are characterised by ineffective erythropoiesis. Luspatercept (ACE-536) is a novel fusion protein that blocks transforming growth factor beta (TGF β) superfamily inhibitors of erythropoiesis, giving rise to a promising new investigative therapy. We aimed to assess the safety and efficacy of luspatercept in patients with anaemia due to lower-risk myelodysplastic syndromes.In this phase 2, multicentre, open-label, dose-finding study (PACE-MDS), with long-term extension, eligible patients were aged 18 years or older, had International Prognostic Scoring System-defined low or intermediate 1 risk myelodysplastic syndromes or non-proliferative chronic myelomonocytic leuk…

AdultMaleIneffective erythropoiesismyalgiamedicine.medical_specialtyPediatricsTime FactorsMaximum Tolerated DoseAnemiaActivin Receptors Type IIRecombinant Fusion ProteinsKaplan-Meier EstimateLower riskmedicine.disease_causeRisk AssessmentSeverity of Illness IndexDisease-Free SurvivalDrug Administration Schedule03 medical and health sciences0302 clinical medicineGermanyInternal medicineSeverity of illnessmedicineHumansProspective StudiesProspective cohort studyAdverse effectAgedProportional Hazards ModelsDose-Response Relationship Drugbusiness.industryMyelodysplastic syndromesAnemiaMiddle AgedPrognosismedicine.diseaseSurvival AnalysisActivinsImmunoglobulin Fc FragmentsTreatment OutcomeOncologyMyelodysplastic Syndromes030220 oncology & carcinogenesisFemalemedicine.symptombusiness030215 immunologyThe Lancet Oncology
researchProduct