𝛽-thalassemia is the most common thalassemia syndrome, characterized by defective production of 𝛽-globin chains, leading to ineffective erythropoiesis. Standard care has been red blood cell (RBC) transfusions, but those have limitations.

A review article published in Blood Advances discusses the pharmacology and future directions of luspatercept for 𝛽-thalassemia and other types of anemia that involve ineffective erythropoiesis.

Luspatercept is an activin receptor ligand trap currently approved in the United States and Europe to treat anemia in adults with 𝛽-thalassemia who require regular RBC transfusions. The effectiveness of luspatercept was shown to inhibit late-state erythropoiesis in mouse models. The first study in healthy humans found the drug was well-tolerated, with no serious adverse events.

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A phase 2 study in patients with 𝛽-thalassemia found an erythroid response and reduced red blood cell transfusion burden with luspatercept.

Next came the BELIEVE trial, a randomized, double-blind, placebo-controlled phase 3 trial. The trial enrolled 336 patients with 𝛽-thalassemia who were regularly receiving transfusions. The trial was conducted at 65 sites across 15 countries. Patients received luspatercept or placebo plus best supportive care, which included RBC transfusions and iron chelation therapy.

Out of the patients who received luspatercept, 21.4% achieved the primary endpoint of 33% or greater reduction in transfusion burden, compared to 4.5% with placebo (P <.001). 11% of patients in the luspatercept group achieved transfusion independence during any 8-week interval. Benefits of luspatercept over placebo continued across all prespecified subgroups of patients. The trial has entered a 5-year open-label extension phase.

Luspatercept is also being evaluated in a phase 2 trial (BEYOND; ClinicalTrials.gov identifier: NCT03342404) and in a trial for pediatric patients that is ready to start enrollment (ClinicalTrials.gov identifier: NCT04143724).

Luspatercept shows a greater benefit for patients with non-𝛽0/𝛽0 genotype than in those with a 𝛽0/𝛽0 genotype.

A phase 2 trial (ClinicalTrials.gov identifier: NCT01749514) found a benefit for luspatercept in patients with myelodysplastic syndrome (MDS) or myelomonocytic leukemia. A phase 3 trial focused on patients with lower risk MDS with ring sideroblasts (RS). The MEDALIST trial (ClinicalTrials.gov identifier: NCT02631070) observed a benefit for MDS-RS patients receiving luspatercept.

The study authors conclude that future studies may look at additional uses for luspatercept to treat anemia associated with ineffective erythropoiesis or dyserythropoiesis.

Disclosures: Some authors have declared affiliations with or received grant support from the pharmaceutical industry. Please refer to the original study for a full list of authors’ disclosures.


Cappellini MD, Taher AT. The use of luspatercept for thalassemia in adults. Blood Adv. 2021;5(1):326-333. doi:10.1182/bloodadvances.2020002725