Reblozyl (luspatercept-aamt)

P2, N=20, Not yet recruiting, Institute of Hematology & Blood Diseases Hospital, China

P=N/A, N=200, Recruiting, Bristol-Myers Squibb | Not yet recruiting --> Recruiting | Initiation date: Oct 2025 --> Feb 2026

P=N/A, N=418, Completed, Bristol-Myers Squibb | Active, not recruiting --> Completed | Trial completion date: Jun 2025 --> Mar 2025

Early diagnosis of acute promyelocytic leukemia (APL), driven by PML-RARA oncoprotein, is vital for survival, as delays can cause fatal coagulopathy without prompt therapeutic intervention of all-trans retinoic acid and arsenic trioxide...Pharmacological inhibition of TGF-β1 ligand using luspatercept reduced SMAD phosphorylation and PDPN expression, indicating TGF-β/SMAD transcriptionally regulates PDPN. Additionally, ELISA-based serum profiling showed significantly elevated TGF-β1 levels in APL patients compared to non-APL AML (p < 0.0001). These findings identify PDPN overexpression as a downstream consequence of TGF-β/SMAD signaling and highlight its potential as a diagnostic biomarker for APL.

In this report, the complex mechanism of luspatercept is discussed with a literature review on the clinical trials leading to its approval in MDS patients. Furthermore, we connect the pathophysiology between the formation of this patient's telangiectasias leading to her PAVM with the disruption of the TGF-β/SMAD pathway from luspatercept use.

Clinicians should be aware of possible renal involvement during luspatercept treatment and consider systematic monitoring of kidney function and urinalysis in treated patients. Further data are needed to clarify the spectrum and mechanisms of renal adverse events associated with this drug.

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.