Reblozyl (luspatercept-aamt)

P2, N=20, Not yet recruiting, The First Affiliated Hospital of Zhejiang Chinese Medical University; The First Affiliated Hospital of Zhejiang Chinese Medical University

P1/2, N=46, Recruiting, Zhujiang Hospital

Advances in therapy now directly target these mechanisms: Luspatercept, a TGF-β ligand trap, has transformed care in β-thalassemia and MDS by restoring late-stage differentiation, while anti-inflammatory strategies, metabolic modulators, and gene editing approaches are being actively explored. Together, these discoveries reframe IE as a modifiable process rather than an inevitable consequence of disease. By distinguishing defective from IE and mapping their mechanistic underpinnings, this review outlines how novel therapeutic strategies can improve anemia, reduce systemic complications, and ultimately enhance outcomes in patients with erythroid disorders.

Here we report red blood cell (RBC) transfusion response analysis based on somatic mutations profile and disease risk for patients treated with luspatercept or epoetin alfa in the COMMANDS trial. Luspatercept represents an effective treatment option in various mutational backgrounds in LR MDS. Trial Registration: ClinicalTrials.gov Identifier: NCT03682536.

Two peptide-based ligand traps have recently received clinical approval: luspatercept [ActRIIB-Fc], an erythroid maturation agent, and sotatercept [ActRIIA-Fc], a novel therapeutic agent for pulmonary arterial hypertension [PAH]. Although both agents have failed to increase skeletal muscle mass in clinical trials consistently, they represent significant advances in the treatment of hematopoietic and vascular disorders. Future studies should focus on optimal dosing strategies, long-term safety, and potential synergistic effects when combined with other therapeutic modalities.

Novel agents, including luspatercept, matriptase-2 inhibitors, and anti-hemojuvelin antibodies, represent promising interventions for conditions characterized by ineffective erythropoiesis and iron maldistribution...Critical evaluation of clinical trial evidence reveals both therapeutic promise and implementation challenges, highlighting the need for continued mechanistic research and translational development. Future directions emphasize combination therapeutic strategies, biomarker-driven patient stratification, and the development of targeted interventions addressing the complex interplay between iron metabolism, inflammation, and hematopoietic function.

P2, N=60, Recruiting, Yale University | Not yet recruiting --> Recruiting

P2, N=70, Recruiting, H. Lee Moffitt Cancer Center and Research Institute | Suspended --> Recruiting

New therapeutic options to reduce the red blood cell (RBC) transfusion burden have emerged since 2020 and include luspatercept and imetelstat. Erythropoiesis-stimulating agents and lenalidomide also address anemia and are generally recommended to start at the time of transfusion dependency, although emerging data suggest that an earlier start of these interventions might offer clinical benefits...Targeted therapy directed to the presence of an IDH1 mutation is U.S. Food and Drug Administration (FDA) approved for the rare IDH1 mutated MDS (<10% of the time) and consideration to use an IDH2 inhibitor for IDH2 mutated MDS (<5% of the time) is reasonable. Interestingly, IDH mutations seem to appear with increased frequency in older patients and in patients with underlying autoimmune/rheumatological disorders.1.

P3, N=106, Active, not recruiting, Bristol-Myers Squibb | Trial primary completion date: Jan 2026 --> Oct 2025

Drugs designed to promote erythropoiesis in MDS patients include erythropoiesis-stimulating agents such as recombinant human erythropoietin and TGF-β inhibitors such as luspatercept, which is approved for the treatment of anemia associated with MDS or β-thalassemia...Our findings demonstrate that GATA1 binds to the UBE2O promoter, thereby regulating UBE2O transcription and expression. Although further studies are needed to explore the implications of UBE2O in MDS treatment, our work provides potential strategies for novel therapeutic approaches in MDS.