Efficacy and safety of luspatercept in non–transfusion-dependent β-thalassemia: long-term results from the BEYOND study

Chronic anemia due to non-transfusion-dependent β-thalassemia (NTDT) can result in clinical morbidities, particularly with inadequate management. Luspatercept was previously shown to improve hemoglobin levels in patients with NTDT in the phase 2, randomized, double-blind, placebo-controlled BEYOND trial (ClinicalTrials.gov identifier: NCT03342404). Here, we report long-term efficacy and safety results from the final analysis of BEYOND spanning an additional 26 months (∼2.2 years) of follow-up. Median treatment duration was 202.8 weeks for luspatercept and 61.1 weeks for placebo. Overall, 94.8% and 22.4% of patients in the luspatercept and placebo arms, respectively, achieved a mean hemoglobin increase from baseline ≥1.0 g/dL during any 12-week interval, with mean durations of response of 1136.0 and 203.3 days, respectively. Patient-reported tiredness and weakness showed sustained improvement with luspatercept treatment. The most common treatment-emergent adverse events in the luspatercept group were headache (45.8% vs 20.4% with placebo), bone pain (43.8% vs 6.1%), back pain (39.6% vs 12.2%), and arthralgia (38.5% vs 16.3%). Treatment-emergent extramedullary hematopoiesis events were reported in 12 (9.0%) and 2 (4.1%) patients receiving luspatercept and placebo, respectively, although differences in treatment exposures prevented informative comparisons. Of the 4 patients receiving luspatercept who reported thromboembolic events, all had >1 risk factor. These results show that luspatercept led to a sustained increase in hemoglobin levels in patients with NTDT for up to ∼4.6 years of treatment, with a consistent safety profile and no new safety findings. Luspatercept is a valuable treatment option for patients with NTDT, addressing the need for effective long-term treatment of anemia. This trial was registered at www.clinicaltrials.gov as #NCT03342404.

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Publication Details

Journal
Blood Advances
Published
2025-08-28
DOI
https://doi.org/10.1182/bloodadvances.2025016554
Citations
3
Primary Topic
Hemoglobinopathies and Related Disorders
Type
article
Field-Weighted Citation Impact
4.88

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article

Efficacy and safety of luspatercept in non–transfusion-dependent β-thalassemia: long-term results from the BEYOND study

Oriana Esposito, Luciana Moro Bueno, Silverio Perrotta, John B. Porter et al.
3 citations
Blood Advances
Hemoglobinopathies and Related Disorders
4.88
article

Efficacy and safety of luspatercept in non–transfusion-dependent β-thalassemia: long-term results from the BEYOND study

Oriana Esposito, Luciana Moro Bueno, Silverio Perrotta, John B. Porter, Antonis Kattamis, Paolo Ricchi, Khaled M. Musallam, Gian Luca Forni, Maria Domenica Cappellini, Yinzhi Lai, Richard Pilot, Alì Taher, Thomas D. Coates, Wen‐Ling Kuo, Vip Viprakasit, Richard Wei�, Marta Reverte
article en
3 citations

Abstract

Chronic anemia due to non-transfusion-dependent β-thalassemia (NTDT) can result in clinical morbidities, particularly with inadequate management. Luspatercept was previously shown to improve hemoglobin levels in patients with NTDT in the phase 2, randomized, double-blind, placebo-controlled BEYOND trial (ClinicalTrials.gov identifier: NCT03342404). Here, we report long-term efficacy and safety results from the final analysis of BEYOND spanning an additional 26 months (∼2.2 years) of follow-up. Median treatment duration was 202.8 weeks for luspatercept and 61.1 weeks for placebo. Overall, 94.8% and 22.4% of patients in the luspatercept and placebo arms, respectively, achieved a mean hemoglobin increase from baseline ≥1.0 g/dL during any 12-week interval, with mean durations of response of 1136.0 and 203.3 days, respectively. Patient-reported tiredness and weakness showed sustained improvement with luspatercept treatment. The most common treatment-emergent adverse events in the luspatercept group were headache (45.8% vs 20.4% with placebo), bone pain (43.8% vs 6.1%), back pain (39.6% vs 12.2%), and arthralgia (38.5% vs 16.3%). Treatment-emergent extramedullary hematopoiesis events were reported in 12 (9.0%) and 2 (4.1%) patients receiving luspatercept and placebo, respectively, although differences in treatment exposures prevented informative comparisons. Of the 4 patients receiving luspatercept who reported thromboembolic events, all had >1 risk factor. These results show that luspatercept led to a sustained increase in hemoglobin levels in patients with NTDT for up to ∼4.6 years of treatment, with a consistent safety profile and no new safety findings. Luspatercept is a valuable treatment option for patients with NTDT, addressing the need for effective long-term treatment of anemia. This trial was registered at www.clinicaltrials.gov as #NCT03342404.

Blood AdvancesVol. 9(23)
University of Southern California (US), University College Hospital (GB), Siriraj Hospital (TH), Children's Hospital of Los Angeles (US), University College London Hospitals NHS Foundation Trust (GB), Khalifa University of Science and Technology (AE), University of Campania "Luigi Vanvitelli" (IT), National and Kapodistrian University of Athens (GR), Cornell University (US), Emirates Foundation (AE), Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico (IT), Ente Ospedaliero Ospedali Galliera (IT), Ospedale Antonio Cardarelli (IT), Bristol-Myers Squibb (United States) (US), American University of Beirut Medical Center (LB), Center for Cancer and Blood Disorders (US), University of Campania "Luigi Vanvitelli" (IT), Center for Cancers and Blood Disorders (US), Bristol-Myers Squibb (Belgium) (BE), Azienda di Rilievo Nazionale ed Alta Specializzazione (IT), University College London (GB), Bristol-Myers Squibb (Switzerland) (CH)
Bristol-Myers Squibb, Sanofi, Celgene, Acceleron, Agios Pharmaceuticals, Vifor Pharma, Silence Therapeutics
Openalex Percentile: Top 5%
Hemoglobinopathies and Related Disorders
4.88
DOIOpen Access PDFOpenAlex
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