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Luspatercept: A Review in Transfusion-Dependent Anaemia due to Myelodysplastic Syndromes or β-Thalassaemia

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Abstract

Luspatercept (Reblozyl®), a first-in-class erythroid maturation agent, is approved in several countries worldwide for the treatment of adults with transfusion-dependent anaemia due to myelodysplastic syndromes (MDS), who have failed prior erythropoiesis-stimulating therapy, or β-thalassaemia. In pivotal, placebo-controlled, phase III trials, subcutaneous luspatercept significantly reduced red blood cell (RBC) transfusion requirements in patients with MDS or β-thalassaemia. Luspatercept had a generally manageable tolerability profile in clinical trials. Adverse events of special interest include thromboembolic events, hypertension and bone pain. Thus, luspatercept is an emerging treatment option in adults with transfusion-dependent anaemia due to MDS or β-thalassaemia.

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References

  1. Cappellini MD, Cohen A, Porter J, et al. Guidelines for the management of transfusion dependent thalassaemia (TDT). 3rd ed. Nicosia (CY): Thalassaemia International Federation; 2014.

    Google Scholar 

  2. Fenaux P, Haase D, Sanz GF, et al. Myelodysplastic syndromes: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2014;25(Suppl 3):iii57–69.

    Article  Google Scholar 

  3. Hellström-Lindberg E, Tobiasson M, Greenberg P. Myelodysplastic syndromes: moving towards personalized management. Haematologica. 2020;105(7):1765–79.

    Article  Google Scholar 

  4. Komrokji RS. Luspatercept in myelodysplastic syndromes: who and when? Hematol Oncol Clin N Am. 2020;34(2):393–400.

    Article  Google Scholar 

  5. National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in oncology: myelodysplastic syndromes (ver 3.2021). 2020. https://www.nccn.org. Accessed 21 Apr 2021.

  6. Sharma A, Mathew ME, Puri L. Splenectomy for people with thalassaemia major or intermedia. Cochrane Database Syst Rev. 2019;9(9):CD010517.

    PubMed  Google Scholar 

  7. Killick SB, Carter C, Culligan D, et al. Guidelines for the diagnosis and management of adult myelodysplastic syndromes. Br J Haematol. 2013;164(4):503–25.

    Article  Google Scholar 

  8. Fenaux P, Kiladjian JJ, Platzbecker U. Luspatercept for the treatment of anemia in myelodysplastic syndromes and primary myelofibrosis. Blood. 2019;133(8):790–4.

    Article  CAS  Google Scholar 

  9. Germing U, Oliva EN, Hiwase D, et al. Treatment of anemia in transfusion-dependent and non-transfusion-dependent lower-risk MDS: current and emerging strategies. Hemasphere. 2019;3(6):e314.

    Article  Google Scholar 

  10. European Medicines Agency. Reblozyl® (luspatercept): EU summary of product characteristics. 2020. https://www.ema.europa.eu. Accessed 21 Apr 2021.

  11. Celgene Corporation. REBLOZYL® (luspatercept-aamt): US prescribing information. 2020. https://www.fda.gov. Accessed 21 Apr 2021.

  12. Suragani R, Cawley SM, Li R, et al. Modified activin receptor IIB ligand trap mitigates ineffective erythropoiesis and disease complications in murine β-thalassemia. Blood. 2014;123(25):3864–72.

    Article  CAS  Google Scholar 

  13. Suragani R, Cadena SM, Cawley SM, et al. Transforming growth factor-β superfamily ligand trap ACE-536 corrects anemia by promoting late-stage erythropoiesis. Nat Med. 2014;20(4):408–14.

    Article  CAS  Google Scholar 

  14. Attie KM, Allison MJ, McClure T, et al. A phase 1 study of ACE-536, a regulator of erythroid differentiation, in healthy volunteers. Am J Hematol. 2014;89(7):766–70.

    Article  CAS  Google Scholar 

  15. Chen NH, Kassir N, Laadem A, et al. Population pharmacokinetics and exposure-response relationship of luspatercept, an erythroid maturation agent, in anemic patients with β-thalassemia. CPT Pharmacometrics Syst Pharmacol. 2020;9(7):395–404.

    Article  CAS  Google Scholar 

  16. Fenaux P, Platzbecker U, Mufti GJ, et al. Luspatercept in patients with lower-risk myelodysplastic syndromes. N Engl J Med. 2020;382(2):140–51.

    Article  CAS  Google Scholar 

  17. Platzbecker U, Germing U, Gotze KS, et al. Luspatercept for the treatment of anaemia in patients with lower-risk myelodysplastic syndromes (PACE-MDS): a multicentre, open-label phase 2 dose-finding study with long-term extension study. Lancet Oncol. 2017;18(10):1338–47.

    Article  CAS  Google Scholar 

  18. Piga A, Perrotta S, Gamberini MR, et al. Luspatercept improves hemoglobin levels and blood transfusion requirements in a study of patients with β-thalassemia. Blood. 2019;133(12):1279–89.

    Article  CAS  Google Scholar 

  19. Fenaux P, Santini V, Mufti GJ, et al. Effects of luspatercept on serum ferritin in patients (pts) with lower-risk myelodysplastic syndromes (MDS) with ring sideroblasts (RS) in the phase 3 MEDALIST trial. 2020;25th Congress of the European Haematology Association.

  20. Fenaux P, Mufti GJ, Buckstein R, et al. Assessment of longer-term efficacy and safety in the phase 3, randomized, double-blind, placebo-controlled MEDALIST trial of luspatercept to treat anemia in patients (pts) with revised International Prognostic Scoring System (IPSS-R) very low-, low-, or intermediate-risk myelodysplastic syndromes (MDS) with ring sideroblasts (RS) who require red blood cell (RBC) transfusions [abstract no. 841 plus presentation]. Blood. 2019;134(Suppl 1):841.

    Article  Google Scholar 

  21. Cappellini MD, Viprakasit V, Taher AT, et al. A phase 3 trial of luspatercept in patients with transfusion-dependent β-thalassemia. N Engl J Med. 2020;382(13):1219–31.

    Article  CAS  Google Scholar 

  22. Taher A, Viprakasit V, Cappellini MD, et al. Assessment of longer-term efficacy and safety in the phase 3 BELIEVE trial of luspatercept to treat anemia in patients (pts) with β-thalassemia. 2020;25th Congress of the European Haematology Association.

  23. European Medicines Agency. Reblozyl® (luspatercept): EPAR - public assessment report. 2020. https://www.ema.europa.eu. Accessed 21 Apr 2021.

  24. Langhi D Jr, Ubiali EMA, Marques JFC Jr, et al. Guidelines on beta-thalassemia major—regular blood transfusion therapy: Associac¸ão Brasileira de Hematologia, Hemoterapia e Terapia Celular: project guidelines: Associac¸ão Médica Brasileira—2016. Rev Bras Hematol Hemoter. 2016;38(4):341–5.

    Article  Google Scholar 

  25. Malcovati L, Stevenson K, Papaemmanuil E, et al. SF3B1-mutant MDS as a distinct disease subtype: a proposal from the International Working Group for the Prognosis of MDS. Blood. 2020;136(2):157–70.

    Article  CAS  Google Scholar 

  26. Taher A, Ismaeel H, Mehio G, et al. Prevalence of thromboembolic events among 8,860 patients with thalassaemia major and intermedia in the Mediterranean area and Iran. Thromb Haemost. 2006;96(4):488–91.

    Article  CAS  Google Scholar 

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Acknowledgements

During the peer review process, the manufacturer of luspatercept was also offered an opportunity to review this article. Changes resulting from comments received were made on the basis of scientific and editorial merit.

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Authors and Affiliations

  1. Springer Nature, Private Bag 65901, Mairangi Bay, Auckland, 0754, New Zealand

    Connie Kang & Yahiya Y. Syed

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  1. Connie Kang
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  2. Yahiya Y. Syed
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Corresponding author

Correspondence to Connie Kang.

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Funding

The preparation of this review was not supported by any external funding.

Authorship and Conflict of interest

Connie Kang and Yahiya Y. Syed are salaried employees of Adis International Ltd/Springer Nature, and declare no relevant conflicts of interest. All authors contributed to the review and are responsible for the article content.

Ethics approval, Consent to participate, Consent to publish, Availability of data and material, Code availability

Not applicable.

Additional information

The manuscript was reviewed by: D. Farmakis, University of Cyprus Medical School, Nicosia, Cyprus; M. Angastiniotis, Thalassaemia International Federation, Nicosia, Cyprus.

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Kang, C., Syed, Y.Y. Luspatercept: A Review in Transfusion-Dependent Anaemia due to Myelodysplastic Syndromes or β-Thalassaemia. Drugs 81, 945–952 (2021). https://doi.org/10.1007/s40265-021-01527-9

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  • DOI: https://doi.org/10.1007/s40265-021-01527-9

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