Luspatercept recently received marketing authorization through the European Union (EU) to treat select patients with myelodysplastic syndromes (MDS) or with transfusion-dependent beta thalassemia (BT). An article in HemaSphere reviewed the application for luspatercept.

The EU approved luspatercept for adults with transfusion-dependent anemia because of very low-, low-, and intermediate-risk MDS with ring sideroblasts who did not respond to or are ineligible for erythropoietin-based therapy.

Erythropoiesis-stimulating agents (ESAs) are the first-line treatment for patients with low-risk MDS. Patients who do not respond to ESAs have few treatment options and often need long-term red blood cell (RBC) transfusions.

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Patients with BT may also become RBC transfusion dependent despite more available treatment options, including splenectomy, allogeneic hematopoietic cell transplantation, and betibeglogene autotemcel for patients with a non-β0β0 genotype.

The review defines luspatercept as a “recombinant fusion protein that selectively binds to ligands belonging to the transforming growth factor-beta (TGF-beta) superfamily.” Pharmacodynamic evaluations showed luspatercept led to a dose-dependent hemoglobin increase in the target population.

In total, 9 trials made up the clinical development program for the treatment. The most common treatment-emergent adverse events (TEAEs) for luspatercept across studies were headache, back pain, bone pain, arthralgia, diarrhea, fatigue, pyrexia, and cough.

Grade 3 or greater TEAEs were higher in the pool luspatercept treatment group than the placebo group. A safety analysis found now signal that patients with low-risk MDS are at increased risk of transforming to high-risk MDS or acute myeloid leukemia. The BT data pool reported no malignancies.

Results from 2 phase 3 trials find that luspatercept 37.91% of patients with MDS achieved RBC transfusion independence for 8 weeks or longer. A total of 21.4% of patients with BT achieved RBC transfusion reduction of 33% or more from baseline to weeks 13-14. With these results, luspatercept met the primary endpoints for each study.

Luspatercept addresses an unmet need in patients with MDS who no longer respond to ESAs to reduce their transfusion burden. Based on these results, the EU concluded the risk-benefit balance of luspatercept was positive for this patient population.


Delgado J, Voltz C, Stain M, et al. The European Medicines Agency review of luspatercept for the treatment of adult patients with transfusion-dependent anemia caused by low-risk myelodysplastic syndromes with ring sideroblasts or beta-thalassemia. Hemasphere. 2021;5(8):e616. doi:10.1097/HS9.0000000000000616