Luspatercept for the Treatment of Anemia in Non-Transfusion-Dependent β-Thalassemia: Final Safety and Efficacy Data from the BEYOND Trial

Background: Suboptimal anemia management in patients (pts) with non-transfusion-dependent (NTD) β-thalassemia may lead to serious clinical complications. Improvements in hemoglobin (Hb) levels were shown to significantly decrease the risk of developing morbidities (Musallam KM, et al. Ann Hematol 20...

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Published in:Blood 2023-11, Vol.142 (Supplement 1), p.3847-3847
Main Authors: Taher, Ali T, Viprakasit, Vip, Kattamis, Antonis, Perrotta, Silverio, Ricchi, Paolo, Porter, John B., Coates, Thomas D, Forni, Gian Luca, Musallam, Khaled M., Esposito, Oriana, Giuseppi, Ana Carolina, Kuo, Wen-Ling, Reverte, Marta, Wei, Richard, Moro Bueno, Luciana, Cappellini, Maria Domenica
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Language:English
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Summary:Background: Suboptimal anemia management in patients (pts) with non-transfusion-dependent (NTD) β-thalassemia may lead to serious clinical complications. Improvements in hemoglobin (Hb) levels were shown to significantly decrease the risk of developing morbidities (Musallam KM, et al. Ann Hematol 2022;101:203-204; Musallam KM, et al. Ann Hematol 2021;100:1903-1905). There is a need for therapies that increase Hb levels besides red blood cell transfusions (RBCT), which lead to secondary iron overload. Primary and longer-term data from the BEYOND study showed that luspatercept led to significant increases in Hb levels and had a manageable safety profile in pts with NTD β-thalassemia (Taher AT, et al. Lancet Haematol 2022;9:e733-e744; Taher AT, et al. Blood 2022;140[suppl 1];8210-8212). Here we report the final data (up to last patient last visit [LPLV] date Nov 28, 2022), of the phase 2, randomized, double-blind, placebo-controlled BEYOND trial (NCT03342404). Methods: Eligible pts (N = 145) had NTD (defined as receiving ≤ 5 RBC units in the 24 wk before randomization) β-thalassemia or HbE/β-thalassemia, Hb levels ≤ 10 g/dL. Pts were randomized to luspatercept (N = 96; 1.0-1.25 mg/kg) or placebo (N = 49) subcutaneously Q3W for ≥ 48 wk. Pts continued to receive best supportive care when required. Pts who crossed over from placebo to luspatercept were not included in this analysis. Mean Hb increase ≥ 1.0 g/dL (any 12-/24-wk interval) and ≥ 1.5 g/dL from baseline (any 12-wk interval), duration of mean Hb increase ≥ 1.0 g/dL and ≥ 1.5 g/dL from baseline, iron parameters, RBCT, and safety were evaluated up to the LPLV date. Results: As of Nov 28, 2022, 93/134 (69.4%) pts on luspatercept transitioned to the long-term follow-up study (NCT04064060): 66/96 (68.8%) pts in the luspatercept arm and 27/38 (71.1%) pts who crossed over from placebo to luspatercept after study unblinding. A total of 76/96 (79.2%) pts in the luspatercept arm completed 144 wk of treatment (tx), with 55/96 (57.3%) completing 192 wk of tx; 28/96 (29.2%) pts on luspatercept discontinued tx. The median (range) luspatercept tx duration was 202.8 (15.0-242.3) wk (Table) and 61.1 (3.0-138.0) wk with placebo. Pts had a durable increase in Hb ≥ 1.0 g/dL from baseline (by 12-wk interval) through wk 240 of luspatercept tx (Figure). In the luspatercept arm, 91/96 (94.8%) pts had a mean Hb increase ≥ 1.0 g/dL from baseline during any 12-wk interval (Table). The mean (standard deviation [SD]) total duration
ISSN:0006-4971
1528-0020
DOI:10.1182/blood-2023-174097