Luspatercept improved anaemia in patients with non-transfusion-dependent β-thalassaemia

Results from the double-blind, multicentre, phase 2 BEYOND study demonstrated that luspatercept is safe and efficacious in patients with non-transfusion-dependent β-thalassaemia (NTDT). A durable increase in haemoglobin levels was achieved, which was associated with increased quality of life scores.

β-thalassemia is an inherited haemoglobinopathy characterised by impaired haemoglobin (Hb) production, chronic anaemia, and iron overload that affects survival and quality of life. Tailored red blood cell transfusions and novel therapies target key pathophysiologic mechanisms in transfusion-dependent β-thalassaemia (TDT) and NTDT. Patients with NTDT do not require lifelong regular transfusion for survival; however, they may require occasional transfusions during pregnancy, surgery, or infection [1].

The Hb level significantly correlates with morbidity-free survival in NTDT: an Hb increase of <8 g/dL to >10 g/dL in steps of 1 g/dL dramatically decreases the development of morbidities [2]. This highlights the need for effective management options for anaemia in NTDT, which are currently unavailable.

Therefore, the BEYOND study (NCT03342404) aimed to determine the safety and efficacy of luspatercept in adult patients with NTDT. Luspatercept is an ActRIIB/IgG1 Fc recombinant fusion protein that has been approved for the treatment of anaemia in adult patients with TDT. Participants were randomised to either 1 mg/kg subcutaneous luspatercept (n=100) or placebo (n=50) every 3 weeks for a duration of at least 48 months. The study was followed by an open-label treatment period and post-treatment follow-up. The primary endpoint was ≥1.0 g/dL mean Hb increase from baseline, in the absence of transfusions, over a 12-week interval from weeks 13 to 24.

Prof. Ali Taher (American University of Beirut Medical Center, Lebanon) presented the first results. The primary endpoint was met: 77.1% of participants treated with luspatercept achieved a mean Hb increase of ≥1.0 g/dL from baseline (P<0.0001), regardless of the baseline being <8.5 or ≥8.5 g/dL and regardless of patient subgroup (see Figure), whereas none of the participants treated with placebo achieved this endpoint. Moreover, 52.1% of participants in the luspatercept arm achieved a mean Hb increase of ≥1.5 g/dL from baseline.

Figure: Subgroup analysis of mean change in Hb from baseline to weeks 13-24 [1]



A key secondary endpoint was improvement in quality of life as assessed in NTDT–patient-reported outcomes (PRO) in the domains of tiredness and weakness (T/W) scores from baseline, which occurred more frequently in patients receiving luspatercept and was consistently improving through week 78. The improvement in NTDT-PRO T/W score was significantly correlated with Hb increase (R= -0.29; P<0.0001). The safety outcomes were similar in both arms; no deaths, malignancies, or thromboembolic events were reported.

Prof. Taher summarised, “The clinical benefit of luspatercept treatment, previously observed in patients with TDT through significant reduction in red blood cell transfusion burden, has now also been observed in patients with NTDT, as measured by meaningful improvement of anaemia.”

1. 
   
   1. Taher AT, et al. The BEYOND study: results of a phase 2, double-blind, randomized, placebo-controlled multicenter study of luspatercept in adult patients with non-transfusion dependent beta-thalassemia. P204-2, EHA 2021 Virtual Congress, 09–17 June.
   2. Musallam KM, et al. Ann Hematol 2021;Feb 11. DOI: 1007/s00277-020-04370-2.

 

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Posted on 5 August 202115 February 2024