2021
DOI: 10.1182/bloodadvances.2020002177 View full text |Buy / Rent full text
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Abstract: Luspatercept (Reblozyl) was recently approved for treating patients with transfusion-dependent lower-risk myelodysplastic syndrome (MDS) with ring sideroblasts (RS) and/or SF3B1 mutation who were not eligible for erythropoiesis-stimulating agents (ESAs) or patients for whom those agents failed. Luspatercept acts as an activin receptor type IIB fusion protein ligand trap that targets the altered transforming growth factor beta pathway in MDS, which is associated with impaired terminal erythroid maturation. Trea… Show more

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“… 128 These results resulted in resulted in approval by both the US FDA and EMA. 129 Sotatercept (ACE-011) has been tested and is under investigation in pre-marketing clinical trials for various uses, including thalassemia and other congenital forms of anemia, myelodysplastic syndrome, multiple myeloma, end stage renal disease, and pulmonary arterial hypertension, with results indicating good tolerability and efficacy. 124 , 130 Interestingly, a Phase II placebo-controlled study evaluated sotatercept for the treatment of anemia associated with platinum-based chemotherapy in patients with advanced/metastatic solid tumors.…”
Section: Therapeutic Approaches For Anemia In Patients With Cancermentioning
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“… 128 These results resulted in resulted in approval by both the US FDA and EMA. 129 Sotatercept (ACE-011) has been tested and is under investigation in pre-marketing clinical trials for various uses, including thalassemia and other congenital forms of anemia, myelodysplastic syndrome, multiple myeloma, end stage renal disease, and pulmonary arterial hypertension, with results indicating good tolerability and efficacy. 124 , 130 Interestingly, a Phase II placebo-controlled study evaluated sotatercept for the treatment of anemia associated with platinum-based chemotherapy in patients with advanced/metastatic solid tumors.…”
Section: Therapeutic Approaches For Anemia In Patients With Cancermentioning
“…MDS-RS have a shorter median duration of response to erythropoietin stimulating agents. Thus the diagnosis is essential, and new drugs for the amelioration of anemia are warranted [ 62 , 65 , 66 ]. While luspatercept is effective for anemia improvement, erythroid amelioration was also obvious in transgenic mice with hematopoiesis-specific GDF11 deletion [ 67 ].…”
Section: Aspects On Iron Ros and Implications For Mdsmentioning
“…Luspatercept has been found to induce transfusion independency for at least 8 weeks in approximately 40% of low-risk MDS patients compared to 13% of patients that were treated with placebo 97 . Luspatercept resembles an activin receptor fusion protein that promotes erythropoiesis by trapping BMP/TGF-β ligands 97,98 . BMP/TGF-β and Wnt/βcatenin signaling closely cooperate to balance cell proliferation and differentiation as outlined above 48,51…”
Section: Wnt/β-catenin Signaling Is Deregulated In Mdsmentioning