Reblozyl (luspatercept-aamt)

Lower-risk myelodysplastic syndromes (MDS) and chronic myelomonocytic leukemia (CMML) are commonly managed with erythropoiesis-stimulating agents, luspatercept, or hypomethylating agents. There were no dose-limiting toxicities. Although safe, fostamatinib demonstrated no clinical benefit, underscoring the need for alternative strategies to modulate inflammatory signaling in MDS/CMML.

P1/2, N=22, Recruiting, Associazione Qol-One | Not yet recruiting --> Recruiting

In aggregate, these findings may contribute to a better understanding of disease pathophysiology and help elucidate the role of potentially clinically relevant TGF-β signaling. This is particularly significant given the clinical use of agents targeting TGF-β-signaling such as luspatercept, as well as the emergence of several CCN2-targeting therapies currently undergoing clinical or preclinical evaluation with promising results.

P2, N=270, Not yet recruiting, National Cancer Institute (NCI)

P=N/A, N=1300, Active, not recruiting, Bristol-Myers Squibb

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