Luspatercept in low-risk myelodysplastic syndromes: a paradigm shift in treatment strategies

References

• Bejar R, Steensma DP. Recent developments in myelodysplastic syndromes. Blood. 2014;124:2793–2803. doi: 10.1182/blood-2014-04-522136
   PubMed Web of Science ®Google Scholar
• Cogle CR, Craig BM, Rollison DE, et al. Incidence of the myelodysplastic syndromes using a novel claims-based algorithm: high number of uncaptured cases by cancer registries. Blood. 2011;117:7121–7125. doi: 10.1182/blood-2011-02-337964
   PubMed Web of Science ®Google Scholar
• Neukirchen J, Schoonen WM, Strupp C, et al. Incidence and prevalence of myelodysplastic syndromes: data from the düsseldorf MDS-registry. Leuk Res. 2011;35(12):1591–1596. doi: 10.1016/j.leukres.2011.06.001
   PubMed Web of Science ®Google Scholar
• Greenberg PL, Tuechler H, Schanz J, et al. Revised international prognostic scoring system for myelodysplastic syndromes. Blood. 2012;120:2454–2465. doi: 10.1182/blood-2012-03-420489
   PubMed Web of Science ®Google Scholar
• A Silva-Coelho P, Kroeze LI, Yoshida K, et al. Clonal evolution in myelodysplastic syndromes. Nat Commun. 2017;8:15099. doi: 10.1038/ncomms15099
   PubMed Web of Science ®Google Scholar
• Bernard E, Tuechler H, Greenberg PL, et al. Molecular international prognostic scoring system for myelodysplastic syndromes. NEJM Evid. 2022;1(7). doi: 10.1056/EVIDoa2200008
   PubMedGoogle Scholar
• 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. doi: 10.1093/annonc/mdu180
   PubMedGoogle Scholar
• Steensma DP, Bennett JM. The myelodysplastic syndromes: diagnosis and treatment. Mayo Clin Proc. 2006;81:104–130. doi: 10.4065/81.1.104
   PubMed Web of Science ®Google Scholar
• European Medicines Agency. Reblozyl® (luspatercept): EU summary of product characteristics. 2020. cited 2021 Apr 21. Available from: https://www.ema.europa.eu
   Google Scholar
• Celgene Corporation. REBLOZYL® (luspatercept-aamt): US prescribing information. 2020.cited 2021 Apr 21. Available from: https://www.fda.gov
   Google Scholar
• Verma A, Suragani RNVS, Aluri S, et al. Biological basis for efficacy of activin receptor ligand traps in myelodysplastic syndromes. J Clin Invest. 2020;130(2):582–589. doi: 10.1172/JCI133678
   PubMed Web of Science ®Google Scholar
• Suragani RNVS, 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):408–414. doi: 10.1038/nm.3512
   PubMed Web of Science ®Google Scholar
• Zermati Y, Fichelson S, Valensi F, et al. Transforming growth factor inhibits erythropoiesis by blocking proliferation and accelerating differentiation of erythroid progenitors. Exp Hematol. 2000;28(8):885–894. doi: 10.1016/S0301-472X(00)00488-4
   PubMed Web of Science ®Google Scholar
• Malik J, Kim AR, Tyre KA, et al. Erythropoietin critically regulates the terminal maturation of murine and human primitive erythroblasts. Haematologica. 2013;98(11):1778–1787. doi: 10.3324/haematol.2013.087361
   PubMed Web of Science ®Google Scholar
• Fenaux P, Platzbecker U, Mufti GJ, et al. Luspatercept in patients with lower-risk myelodysplastic syndromes. N Engl J Med. 2020;382(2):140–151. doi: 10.1056/NEJMoa1908892
   PubMed Web of Science ®Google Scholar
• Platzbecker U, Germing U, Götze 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):1338–1347. doi: 10.1016/S1470-2045(17)30615-0
   PubMed Web of Science ®Google Scholar
• Celgene Corporation highlights of prescribing information for REBLOZYL (luspatercept-aamt). Revised Nov 2019.
   Google Scholar
• Fenaux P, Platzbecker U, Mufti GJ, et al. Luspatercept in patients with lower-risk myelodysplastic syndromes. N Engl J Med. 2020;382:140–151. doi: 10.1056/NEJMoa1908892
   PubMed Web of Science ®Google Scholar
• Platzbecker U, Santini V, Komrokji RS, et al. Long-term utilization and benefit of luspatercept in transfusion-dependent, erythropoiesis-stimulating agent-refractory or -intolerant patients with lower-risk myelodysplastic syndromes with ring sideroblasts. Leukemia. 2023;37:2314–2318. doi: 10.1038/s41375-023-02031-7
   PubMed Web of Science ®Google Scholar
• Garcia-Manero G, Mufti GJ, Fenaux P, et al. Neutrophil and platelet increases with luspatercept in lower-risk MDS: secondary endpoints from the MEDALIST trial. Blood. 2022 Jan 27;139(4):624–629. doi: 10.1182/blood.2021012589
   PubMed Web of Science ®Google Scholar
• Komrokji RS, Platzbecker U, Fenaux P, et al. Luspatercept for myelodysplastic syndromes/myeloproliferative neoplasm with ring sideroblasts and thrombocytosis. Leukemia. 2022;36:1432–1435. doi: 10.1038/s41375-022-01521-4
   PubMed Web of Science ®Google Scholar
• Oliva EO, Platzbecker U, Garcia-Manero G, et al. Health-related quality of life outcomes in patients with myelodysplastic syndromes with ring sideroblasts treated with luspatercept in the medalist phase 3 trial. J Clin Med.2022 Jan;11(1):27.
   Web of Science ®Google Scholar
• Platzbecker U, Götze KS, Kiewe P, et al. Shetty, and Aristoteles Giagounidis. Long-term efficacy and safety of luspatercept for anemia treatment in patients with lower-risk myelodysplastic syndromes: the phase II PACE-MDS study. J Clin Oncol. 2022 Nov 20;40(33):3800–3807. doi: 10.1200/JCO.21.02476
   PubMed Web of Science ®Google Scholar
• Mukherjee S, Brown-Bickerstaff C, Huggar D, et al. Treatment patterns and outcomes among patients with lower-risk myelodysplastic syndromes receiving luspatercept in routine clinical practice in the united states. Hemasphere.2023 Aug;7(Suppl):e648138a.
   Google Scholar
• Lanino L, Restuccia F, Perego A, et al. Real-world efficacy and safety of luspatercept and predictive factors of response in patients with lower risk myelodysplastic syndromes with ring sideroblasts. Am J Hematol.2023 Aug;98(8):E204–E208.
   PubMed Web of Science ®Google Scholar
• Farrukh F, Chetram D, Al-Kali A, et al. Real-world experience with luspatercept and predictors of response in myelodysplastic syndromes with ring sideroblasts. Am J Hematol. 2022 Jun 1;97(6):E210–E214. (Contrary to what was reported in MEDALIST and COMMANDS trials, in this study there was a strictly association between the anemia response after luspatercept and high serum EPO level). doi: 10.1002/ajh.26533
   PubMed Web of Science ®Google Scholar
• Garcia-Manero G, Plazbecker U, Santini V, et al. Efficacy and safety of luspatercept versus epoetin alfa in erythropoiesis-stimulating agent (ESA)-naive patients (pts) with transfusion-dependent (TD) lower-risk myelodysplastic syndromes (LR-MDS): full analysis of the commands trial. Abstract 193. Presented at the 2023 American Society of Hematology Meeting. Dec 9-12, 2023; San Diego, CA.
   Google Scholar
• Gerds AT, Harrison C, Kiladjian J-J, et al. Safety and efficacy of luspatercept for the treatment of anemia in patients with myelofibrosis: results from the ACE-536-MF-001 study. Abstract 7016. Presented at the 2023 American Society of Clinical Oncology Annual Meeting; Jun 5, 2023; Chicago, Illinois.
   Google Scholar
• Mesa RA, Harrison C, Kiladjian J, et al. INDEPENDENCE: a phase 3 study of efficacy and safety of luspatercept versus placebo in patients with myeloproliferative neoplasm-associated myelofibrosis on JAK2 inhibitor therapy and requiring red blood cell transfusions. Presented at: 2021 ASH Annual Meeting; Dec 9-14, 2021; Atlanta, GA. Poster 1490.
   Google Scholar
• Fattizzo B, Versino F, Bortolotti M, et al. Luspatercept in combination with recombinant erythropoietin in patients with myelodysplastic syndrome with ring sideroblasts: stimulating early and late-stage erythropoiesis. Eur J Haematol. 2023;110(5):571–574. doi: 10.1111/ejh.13933
   PubMed Web of Science ®Google Scholar
• Zeidan AM, Platzbecker U, Santini V, et al. Imerge: results from a phase 3, randomized, double-blind, placebo-controlled study of imetelstat in patients (pts) with heavily transfusion dependent (TD) non-del(5q) lower-risk myelodysplastic syndromes (LR-MDS) relapsed/refractory (R/R) to erythropoiesis stimulating agents (ESA). J Clin Oncol. 2023;41(suppl 16):7004. doi: 10.1200/JCO.2023.41.16_suppl.7004
   Web of Science ®Google Scholar
• FibroGen announces results for MATTERHORN, a phase 3 clinical study of roxadustat for the treatment of anemia in patients with myelodysplastic syndromes (MDS). News release. FibroGen, Inc. 2023 May 5. [cited 2023 May 5].
   Google Scholar
• Diez-Campelo M, Ross DM, Giagounidis A, et al. Durable clinical benefit with ker-050 treatment: findings from an ongoing phase 2 study in participants with Lower-Risk MDS. Abstract 196. Presented at the 2023 American Society of Hematology Meeting. Dec 9-12, 2023; San Diego, CA.
   Google Scholar