Luspatercept for the treatment of non-transfusion-dependent β-thalassemia

This article is from NEJM Journal Watch

Luspatercept for Non-Transfusion-Dependent β-Thalassemia

Luspatercept for the treatment of non-transfusion-dependent β-thalassemia

Reviewed by Brady Stein, MD, MHS

Luspatercept increased hemoglobin concentration by at least 1 g/dL
compared to placebo.

In patients with transfusion-dependent β-thalassemia, luspatercept is used to promote the later stages of erythropoiesis and reduce the burden
of transfusion.
Patients with non-transfusion-dependent β-thalassemia have less anaemia than transfusion-dependent patients, but these patients have limited treatment options other than on-demand transfusions, despite higher morbidity, mortality, and poor quality of life
.

The investigators conducted a multicenter, randomized, placebo-controlled phase 2 study in 145 patients with non-transfusion-dependent β-thalassemia (median age, 40 years; 57% female; Median baseline hemoglobin, 8.
2 g/dL) evaluated the efficacy and safety
of luspatercept.
The primary endpoint was the proportion of patients with an increase in mean hemoglobin of
1 g/dL without transfusion during weeks 13~24.

The main results of this study are as follows:

• The study met the primary endpoint; The mean hemoglobin increased by ≥ 1.
  0 g/dL in 77% of patients in the luspatercept group compared to 0%
  in the placebo group.
  

• The key secondary endpoint (patients reporting improvement in fatigue/weakness compared with baseline)
  was not met.
  

• The most common adverse events included bone pain (37%), headache (30%), arthralgia (29%), back pain (28%), prehypertension (23%) and hypertension (20%)
  .
  

comments

These results confirm the utility of luspatercept in patients with non-transfusion-dependent β-thalassemia
.
Although iron parameters (ferritin and liver iron concentration) did not change significantly, the investigators noted that the type and dose of iron chelation therapy were not standardized and the follow-up period was not long enough to observe potential changes
.
Notably, no thromboembolic events
were observed in the study.

Articles that were commented on

Taher AT et al.
Luspatercept for the treatment of anaemia in non-transfusion-dependent β-thalassaemia (BEYOND): A phase 2, randomised, double-blind, multicentre, placebo-controlled trial.
Lancet Haematol 2022 Oct; 9:e733.
(https://doi.
org/10.
1016/S2352-3026(22)00208-3)