Luspatercept in low-risk myelodysplastic syndromes: a paradigm shift in treatment strategies

ABSTRACT

Introduction

In patients with myelodysplastic syndromes (MDS), anemia is prevalent affecting 80%–85% of low-risk (LR-MDS) patients, with 40% eventually requiring red blood cell (RBC) transfusions. Except forlenalidomide, exclusively approved for those with deletion of chromosome 5q,erythropoiesis-stimulating agents (ESAs) are the primary treatment choice for low-risk patients. Those unresponsive to ESAs face limited alternatives, eventually necessitating long-term RBC transfusions, leading to secondary iron overload and adversely affecting quality of life (QoL).

Area covered

Luspatercept is a pioneering erythroid maturation agent. It received approval by both the European Medicines Agency (EMA) and the Food and Drug Administration (FDA) for treating adults experiencing transfusion-dependent anemia associated with LR-MDS or β-thalassemia. Recently, the FDA approved luspatercept as first- line therapy in patients with very low- to intermediate-risk MDS who require RBC transfusions and have not previously received ESAs. This review summarizes the historical impact of luspatercept intreating LR-MDS unresponsive to ESAs and illustrates its potential benefit asfrontline therapy in MDS and its employment in patients with myelofibrosis-induced anemia.

Expert opinion

Luspatercept has revolutionized the therapeutic paradigm of LR-MDS, for which there was a limited therapeutic arsenal, especially in the setting of patients who did not respond or fail after ESA treatment.

KEYWORDS:

• Low-risk myelodysplastic syndromes
• luspatercept
• frontline therapy
• erythtopoiesis stimulating agents
• red blood cells transfusions

Article highlights

• Luspatercept is a new recombinant fusion protein made of modified activin receptor type IIb (ActRIIB)

• Luspatercept, known as Reblozyl®, is a pioneering erythroid maturation agent

• EMA and FDA approved luspatercept for treating patients experiencing transfusion-dependent anemia associated with LR-MDS or β-thalassemia

• FDA approved luspatercept as a first-line therapy in adult patients with very low- to intermediate-risk MDS who have not previously received ESAs and require regular RBC transfusions

• Encouraging results from an ongoing study, shows as luspatercept may positively impact on myelofibrosis-induced anemia in patients with transfusion dependence

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Author contributions

M Molica designed and wrote the paper. M Rossi revised the final version of the manuscript.

Additional information

Funding

This paper was not funded.