Clinical Advances in Hematology & OncologyIs Luspatercept the New Standard of Care in Transfusion-Dependent Low-Risk Myelodysplastic Syndromes?

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Luspatercept emerges as a promising treatment for anemia in patients with low-risk myelodysplastic syndromes (LR-MDS). This monoclonal antibody, which works by binding ligands that activate the TGF-β pathway, has shown significant efficacy in both first- and second-line settings. Recent clinical trials have demonstrated its superiority over traditional erythropoiesis-stimulating agents (ESAs) in achieving transfusion independence and improving hemoglobin levels.

Key Points:

• Luspatercept received FDA approval for second-line treatment in April 2020 based on the MEDALIST trial, which showed 38% of patients achieved transfusion independence lasting 8 weeks or longer vs 13% with placebo.
• The COMMANDS trial led to FDA approval for first-line treatment in August 2023, with 59% of patients achieving transfusion independence for at least 12 weeks vs 31% with ESAs.
• Luspatercept demonstrated a favorable safety profile, with fatigue, diarrhea, asthenia, nausea, and dizziness as the most common adverse events.
• Recent analyses from the COMMANDS study suggest luspatercept’s efficacy is not affected by baseline mutation burden or molecular risk factors, unlike ESAs.
• Luspatercept improved overall hematopoiesis, decreased inflammatory biomarkers, and enhanced erythroid hematologic improvement compared to ESAs.
• The ongoing ELEMENT-MDS study is investigating luspatercept in transfusion-independent patients.
• Luspatercept is gradually becoming the standard of care for anemia in low-risk MDS in the United States and is gaining approval worldwide.

HCN Medical Memo
Luspatercept’s efficacy in both first- and second-line settings for anemia in low-risk MDS patients, coupled with its favorable safety profile, positions it as a potentially practice-changing therapy. Physicians should consider integrating luspatercept into their treatment algorithms for appropriate patients.

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