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Leukemias
Published in Pat Price, Karol Sikora, Treatment of Cancer, 2020
ESAs and lenalidomide are standard therapies for LR-MDS and HMAs for HR-MDS. Luspatercept is now licensed for a subset of LR-MDS. HMAs remain the principal treatment for dysplastic CMML; several approaches including CD123-targeted therapies, such as tagraxofusp, are being tested proliferative CMML. Allografting remains the only treatment option with potentially curative potential.
Precision medicine in myelodysplastic syndromes
Published in Debmalya Barh, Precision Medicine in Cancers and Non-Communicable Diseases, 2018
Advances in supportive care are connected with advances in MDS molecular biology and pathogenesis research (Gill et al., 2016). A new target has emerged in treating MDS-related anemia. Defects in erythroid differentiation lead to increased production of erythropoietin without effective hemoglobin synthesis. Growth differentiation factor GDF11, an important erythropoiesis regulator, accumulates and can be inhibited by transforming growth factor β (TGF-β) superfamily ligand trap strategies (Dussiot et al., 2014; Suragani et al., 2014). Luspatercept is an activin receptor antagonist that functions as a ligand trap for GDF11 and other TGF-β family ligands to suppress Smad2/3 activation and to increase hemoglobin synthesis (Mies et al., 2016; Almeida et al., 2017).
An Expert Overview on Therapies in Non-Transfusion-Dependent Thalassemia: Classical to Cutting Edge in Treatment
Published in Hemoglobin, 2023
Mohammadreza Saeidnia, Pooria Fazeli, Arghavan Farzi, Maryam Atefy Nezhad, Mojtaba Shabani-Borujeni, Mehran Erfani, Gholamhossein Tamaddon, Mehran Karimi
Based on a Phase 1 study in healthy donors, a dose-dependent elevation in Hb level was observed 1 week after initiation of Luspatercept, and maintained for several weeks after cessation of therapy; treatment was well tolerated. An open-label, dose-determining, non-randomized, uncontrolled, Phase 2 study (ClinicalTrials.gov number NCT01749540) was performed in 31 patients with β-TI who received less than 4 units of RBCs within 8 weeks previous to day 1 cycle 1. Luspatercept was injected subcutaneously every 3 weeks at a dose ranging from 0.2 to 1.25 mg/kg. The results of this clinical trial indicated the anemia treated in 58.0% of adult NTDT patients after 2 weeks required transfusion. A Phase 2, double-blind, randomized, placebo-controlled, multicenter study (BEYOND trial, ClinicalTrials.gov, number NCT03342404) was conducted to determine the efficacy and safety of Luspatercept as compared to placebo in adults with NTDT (defined as receiving 0 to 5 units of RBCs during the 24 weeks and RBC transfusion-free for at least ≥8 weeks prior to randomization). The study’s first cessation was the estimation of the proportion of participants with an increase in Hb of higher than 1.0 g/dL from baseline over a 12-week interval in the absence of RBC transfusions.
Luspatercept for β-thalassemia: beyond red blood cell transfusions
Published in Expert Opinion on Biological Therapy, 2021
Ali T. Taher, Maria Domenica Cappellini
Luspatercept is an FDA- and EMA-approved therapy for the treatment of anemia in adults with β-thalassemia who require regular transfusions. Results from a Phase III study indicate that substantial reductions in TB may be achieved in patients with both β0/β0 and non-β0/β0 genotypes. Furthermore, results suggest that luspatercept is well tolerated, with the majority of AEs being transient and manageable. Early results suggest luspatercept may have favorable effects on serum ferritin levels. Studies involving luspatercept for the treatment of β-thalassemia continue in a Phase II trial investigating luspatercept in adults with NTD β-thalassemia and a Phase IIa study evaluating luspatercept in pediatric patients who require regular RBC transfusions.
Drug safety in thalassemia: lessons from the present and directions for the future
Published in Expert Opinion on Drug Safety, 2021
Laura Grech, Janet Sultana, Karen Borg, Joseph Borg
Other drug used in thalassemia include those targeting ineffective erythropoiesis, such as luspatercept, also known as Reblozy® or ACE-536, sotatercept, and ruxolitinib. Luspatercept is an erythroid maturation agent that was approved by FDA in 2019 and by the European Medicines Agency (EMA) in June 2020 for adult patients with β-thalassemia who require regular transfusions while sotatercept and ruxolitinib are still being studied in clinical trials and have not been yet licensed. Luspatercept being a recombinant fusion protein that reduces Smad2/3 signaling by binding to several endogenous TGF-β superfamily ligands [36,37]. It is administered by subcutaneous injection and the starting dose is 1 mg/kg once every 3 weeks. It is recommended prior to each administration to assess and review the levels of hemoglobin. AEs included bone pain, arthralgia, dizziness, and hyperuricemia [38].