Skip to main content
SpringerLink
Log in

The Clinical Efficacy of Epoetin Alfa and Darbepoetin Alfa in Patients with Low-Risk or Intermediate-1-Risk Myelodysplastic Syndrome: Retrospective Multi-center Real-Life Study

  • Original Article
  • Published:
Indian Journal of Hematology and Blood Transfusion Aims and scope Submit manuscript

Abstract

This study aimed to evaluate the clinical efficacy of epoetin alfa and darbepoetin alfa in patients with myelodysplastic syndromes (MDS) in the real-life setting. A total of 204 patients with low-risk or intermediate-1-risk MDS who received epoetin alfa or darbepoetin alfa were included. Hemoglobin levels and transfusion need were recorded before and during 12-month treatment. Hemoglobin levels were significantly higher at each follow up visit when compared to baseline levels in both epoetin alfa (mean ± SD 8.68 ± 1.0 g/dL at baseline vs. 9.83 ± 1.45, 9.99 ± 1.55, 10.24 ± 1.77 and 10.2 ± 1.5 g/dL, respectively) and darbepoetin alfa (8.83 ± 1.09 g/dL at baseline vs. 9.62 ± 1.37, 9.78 ± 1.49, 9.9 ± 1.39 and 10.1 ± 1.5 g/dL, respectively) groups (p < 0.001 for each). Transfusion need significantly decreased from baseline at each study visit in the epoetin alfa group (p < 0.001) and only at the 12th month visit (p < 0.001) in the darbepoetin alfa group. Hemoglobin levels or transfusion need was similar between treatment groups. Overall, 12-month response rate was 58.1% for epoetin alfa and 41.9% for darbepoetin alfa, with no significant difference between treatment groups, whereas higher response rate was noted within the first three months (62.7%) compared to next 9 months (ranged 44.4–60%) of treatment in the epoetin alfa group (p ranged 0.002 to < 0.001). This real-life retrospective study revealed similar efficacy of epoetin alfa and darbepoetin alfa among low risk or intermediate-1 risk MDS patients with no difference in treatment response between treatment groups, whereas a likelihood of earlier treatment response in the epoetin alfa group.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1

Similar content being viewed by others

Data Availability

Raw data can be obtained upon request to the corresponding author (drmaslaner@hotmail.com).

References

  1. Park S, Greenberg P, Yucel A, Farmer C, O’Neill F, De Oliveira BC et al (2019) Clinical effectiveness and safety of erythropoietin-stimulating agents for the treatment of low- and intermediate-1-risk myelodysplastic syndrome: a systematic literature review. Br J Haematol 184:134–160. https://doi.org/10.1111/bjh.15707

    Article  CAS  PubMed  Google Scholar 

  2. Malcovati L, Hellström-Lindberg E, Bowen D, Adès L, Cermak J, Del Cañizo C et al (2013) Diagnosis and treatment of primary myelodysplastic syndromes in adults: recommendations from the European LeukemiaNet. Blood 122:2943–2964. https://doi.org/10.1182/blood-2013-03-492884

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Fenaux P, Haase D, Sanz GF, Santini V, Buske C; ESMO Guidelines Working Group (2017) Myelodysplastic syndromes: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol 25(Suppl 3):iii57–iii69. https://doi.org/10.1093/annonc/mdu180

  4. National Comprehensive Cancer Network, Myelodysplastic Syndromes Version 2. 2019. https://www.nccn.org/professionals/physician_gls/default.aspx. Accessed 15 Jan 2021

  5. Killick SB, Carter C, Culligan D, Dalley C, Das-Gupta E, Drummond M et al (2014) Guidelines for the diagnosis and management of adult myelodysplastic syndromes. Br J Haematol 164:503–525. https://doi.org/10.1111/bjh.12694

    Article  CAS  PubMed  Google Scholar 

  6. Park S, Grabar S, Kelaidi C, Beyne-Rauzy O, Picard F, Bardet V et al (2008) Predictive factors of response and survival in myelodysplastic syndrome treated with erythropoietin and G-CSF: the GFM experience. Blood 111:574–582. https://doi.org/10.1182/blood-2007-06-096370

    Article  CAS  PubMed  Google Scholar 

  7. Duong VH, Baer MR, Hendrick F, Weiss SR, Sato M, Zeidan AM et al (2015) Variations in erythropoiesis-stimulating agent administration in transfusion-dependent myelodysplastic syndromes impact response. Leuk Res 39:586–591. https://doi.org/10.1016/j.leukres.2015.03.013

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Greenberg PL, Attar E, Bennett JM, Bloomfield CD, Borate U, De Castro CM et al (2013) Myelodysplastic syndromes: clinical practice guidelines in oncology. J Natl Compr Canc Netw 11:838–874. https://doi.org/10.6004/jnccn.2013.0104

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Greenberg P, Cox C, LeBeau MM, Fenaux P, Morel P, Sanz G et al (1997) International scoring system for evaluating prognosis in myelodysplastic syndromes. Blood 89:2079–2088

    Article  CAS  Google Scholar 

  10. Tefferi A, Barosi G, Mesa RA, Cervantes F, Deeg HJ, Reilly JT et al (2006) International Working Group (IWG) consensus criteria for treatment response in myelofibrosis with myeloid metaplasia, for the IWG for Myelofibrosis Research and Treatment (IWG-MRT). Blood 108:1497–1503. https://doi.org/10.1182/blood-2006-03-009746

    Article  CAS  PubMed  Google Scholar 

  11. Platzbecker U, Symeonidis A, Oliva EN, Goede JS, Delforge M, Mayer J et al (2017) A phase 3 randomized placebo-controlled trial of darbepoetin alfa in patients with anemia and lower-risk myelodysplastic syndromes. Leukemia 31:1944–1950. https://doi.org/10.1038/leu.2017.192

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Fenaux P, Santini V, Spiriti MAA, Giagounidis A, Schlag R, Radinoff A et al (2018) A phase 3 randomized, placebo-controlled study assessing the efficacy and safety of epoetin-α in anemic patients with low-risk MDS. Leukemia 32:2648–2658. https://doi.org/10.1038/s41375-018-0118-9

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Gabrilove J, Paquette R, Lyons RM, Mushtaq C, Sekeres MA, Tomita D et al (2008) Phase 2, single-arm trial to evaluate the effectiveness of darbepoetin alfa for correcting anaemia in patients with myelodysplastic syndromes. Br J Haematol 142:379–393. https://doi.org/10.1111/j.1365-2141.2008.07181.x

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Gotlib J, Lavori P, Quesada S, Stein RS, Shahnia S, Greenberg PL (2009) A Phase II intra-patient dose-escalation trial of weight-based darbepoetin alfa with or without granulocyte-colony stimulating factor in myelodysplastic syndromes. Am J Hematol 84:15–20. https://doi.org/10.1002/ajh.21316

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Oliva EN, Nobile F, Alimena G, Specchia G, Danova M, Rovati B et al (2010) Darbepoetin alfa for the treatment of anemia associated with myelodysplastic syndromes: efficacy and quality of life. Leuk Lymphoma 51:1007–1014. https://doi.org/10.3109/10428191003728610

    Article  CAS  PubMed  Google Scholar 

  16. Villegas A, Arrizabalaga B, Fernández-Lago C, Castro M, Mayans JR, González-Porras JR et al (2011) Darbepoetin alfa for anemia in patients with low or intermediate-1 risk myelodysplastic syndromes and positive predictive factors of response. Curr Med Res Opin 27:951–960. https://doi.org/10.1185/03007995.2011.561834

    Article  CAS  PubMed  Google Scholar 

  17. Kelaidi C, Beyne-Rauzy O, Braun T, Sapena R, Cougoul P, Adès L et al (2013) High response rate and improved exercise capacity and quality of life with a new regimen of darbepoetin alfa with or without filgrastim in lower-risk myelodysplastic syndromes: a phase II study by the GFM. Ann Hematol 92:621–631. https://doi.org/10.1007/s00277-013-1686-4

    Article  CAS  PubMed  Google Scholar 

  18. Houston BL, Jayakar J, Wells RA, Lenis M, Zhang L, Zhu N et al (2017) A predictive model of response to erythropoietin stimulating agents in myelodysplastic syndrome: from the Canadian MDS patient registry. Ann Hematol 96:2025–2029. https://doi.org/10.1007/s00277-017-3137-0

    Article  CAS  PubMed  Google Scholar 

  19. Sekeres MA, Zell K, Barnard J, DeZern AE, Steensma DP, Zimmerman C et al (2015) Long-term outcome of myelodysplastic syndromes (MDS) patients treated with erythropoiesis stimulating agents (ESAs) [abstract]. Blood 126:1696. https://doi.org/10.1182/blood.V126.23.1696.1696

    Article  Google Scholar 

  20. Park S, Fenaux P, Greenberg P, Mehta B, Callaghan F, Kim C et al (2016) Efficacy and safety of darbepoetin alpha in patients with myelodysplastic syndromes: a systematic review and meta-analysis. Br J Haematol 174:730–747. https://doi.org/10.1111/bjh.14116

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Moyo V, Lefebvre P, Duh MS, Yektashenas B, Mundle S (2008) Erythropoiesis-stimulating agents in the treatment of anemia in myelodysplastic syndromes: a meta-analysis. Ann Hematol 87:527–536. https://doi.org/10.1007/s00277-008-0450-7

    Article  CAS  PubMed  Google Scholar 

  22. Patton JF, Sullivan T, Mun Y, Reeves T, Rossi G, Wallace JF (2005) A retrospective cohort study to assess the impact of therapeutic substitution of darbepoetin alfa for epoetin alfa in anemic patients with myelodysplastic syndrome. J Support Oncol 3:419–426

    CAS  PubMed  Google Scholar 

  23. Latagliata R, Oliva EN, Volpicelli P, Carmosino I, Breccia M, Vincelli I et al (2008) Twice-weekly high-dose rHuEpo for the treatment of anemia in patients with low-risk myelodysplastic syndromes. Acta Haematol 120:104–107. https://doi.org/10.1159/000166864

    Article  CAS  PubMed  Google Scholar 

  24. Pelizzari AM, Borlenghi E, Mariotti J, Riva M, Molteni A, Lambertenghi D et al (2016) Biosimilar erythropoietin alfa for the therapy of anemia in “Lower Risk” myelodysplastic syndromes. Interim results from a prospective observational study of the “Rete Ematologica Lombarda” (Eporel) [abstract]. Haematologica 101:775.

  25. Davidoff AJ, Weiss SR, Baer MR, Ke X, Hendrick F, Zeidan A et al (2013) Patterns of erythropoiesis-stimulating agent use among Medicare beneficiaries with myelodysplastic syndromes and consistency with clinical guidelines. Leuk Res 37:675–680. https://doi.org/10.1016/j.leukres.2013.02.021

    Article  PubMed  PubMed Central  Google Scholar 

  26. Turkish Society of Hematology (2020) Guidelines for the diagnosis and management of myelodysplastic syndrome. Galenos Publisher, Ankara, September 2020. www.thd.org.tr. Accessed 20 Jan 2021

  27. Santini V (2011) Clinical use of erythropoietic stimulating agents in myelodysplastic syndromes. Oncologist 16(Suppl 3):35–42. https://doi.org/10.1634/theoncologist.2011-S3-35

    Article  PubMed  Google Scholar 

  28. Terpos E, Mougiou A, Kouraklis A, Chatzivassili A, Michalis E, Giannakoulas N et al (2002) Prolonged administration of erythropoietin increases erythroid response rate in myelodysplastic syndromes: a phase II trial in 281 patients. Br J Haematol 118:174–180. https://doi.org/10.1046/j.1365-2141.2002.03583.x

    Article  CAS  PubMed  Google Scholar 

  29. Greenberg PL, Sun Z, Miller KB, Bennett JM, Tallman MS, Dewald G et al (2009) Treatment of myelodysplastic syndrome patients with erythropoietin with or without granulocyte colony-stimulating factor: results of a prospective randomized phase 3 trial by the Eastern Cooperative Oncology Group (E1996). Blood 114:2393–2400. https://doi.org/10.1182/blood-2009-03-211797

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Gascón P, Krendyukov A, Mathieson N, Aapro M (2019) Epoetin alfa for the treatment of myelodysplastic syndrome-related anemia: a review of clinical data, clinical guidelines, and treatment protocols. Leuk Res 81:35–42. https://doi.org/10.1016/j.leukres.2019.03.006

    Article  CAS  PubMed  Google Scholar 

  31. Kelaidi C, Fenaux P (2010) Darbepoetin alfa in anemia of myelodysplastic syndromes: present and beyond. Expert Opin Biol Ther 10:605–614. https://doi.org/10.1517/14712591003709713

    Article  CAS  PubMed  Google Scholar 

  32. Santini V (2015) Anemia as the main manifestation of myelodysplastic syndromes. Semin Hematol 52:348–356. https://doi.org/10.1053/j.seminhematol.2015.06.002

    Article  PubMed  Google Scholar 

  33. Moura ATG, Duarte FB, Barbosa MC, Santos TEJD, Lemes RPG (2019) Prolonged response to recombinant human erythropoietin treatment in patients with myelodysplastic syndrome at a single referral centre in Brazil. Clinics (Sao Paulo) 74:e771. https://doi.org/10.6061/clinics/2019/e771

    Article  Google Scholar 

  34. Park S, Kelaidi C, Sapena R, Vassilieff D, Beyne-Rauzy O, Coiteux V et al (2010) Early introduction of ESA in low risk MDS patients may delay the need for RBC transfusion: a retrospective analysis on 112 patients. Leuk Res 34:1430–1436. https://doi.org/10.1016/j.leukres.2010.05.030

    Article  PubMed  Google Scholar 

  35. Hellström-Lindberg E, Gulbrandsen N, Lindberg G, Ahlgren T, Dahl IM, Dybedal I et al (2003) A validated decision model for treating the anaemia of myelodysplastic syndromes with erythropoietin + granulocyte colony-stimulating factor: significant effects on quality of life. Br J Haematol 120:1037–1046. https://doi.org/10.1046/j.1365-2141.2003.04153.x

    Article  PubMed  Google Scholar 

  36. Cortesão E, Tenreiro R, Ramos S, Pereira M, César P, Carda JP et al (2015) Eritropoietina Sérica como Marcador Prognóstico em Síndrome Mielodisplásica [Serum Erythropoietin as Prognostic Marker in Myelodysplastic Syndromes]. Acta Med Port 28:720–725

    Article  Google Scholar 

  37. Stevenson JG, Natale JJ (2007) Darbepoetin alfa: an effective treatment with flexible and simplified dosing for anemia in patients with cancer. Pharmacotherapy 27:434–446. https://doi.org/10.1592/phco.27.3.434

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

The preliminary findings of this study were presented in a poster session at the VII. International Eurasian Hematology Congress which was held on October 13, 2016–October 16, 2016 in Istanbul, Turkey—and the abstract was published in Leukemia Research, Volume 49, Supplement 1, October 2016.

Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Author information

Authors and Affiliations

  1. Department of Hematology, Zonguldak Bulent Ecevit University Faculty of Medicine, Incivez, 67100, Zonguldak, Turkey

    Muzeyyen Aslaner Ak, Birsen Sahip & Sehmus Ertop

  2. Department of Hematology, Kocaeli University Faculty of Medicine, Kocaeli, Turkey

    Ayfer Geduk & Merve Gokcen Polat

  3. Department of Hematology, Cukurova University Faculty of Medicine, Adana, Turkey

    Mehmer Ali Ucar & Birol Guvenc

  4. Department of Hematology, Adnan Menderes University Faculty of Medicine, Aydin, Turkey

    Hacer Kale & Ali Zahit Bolaman

  5. Department of Hematology, Sakarya Training and Research Hospital, Sakarya, Turkey

    Tugba Hacibekiroglu & Yasin Kalpakci

Authors
  1. Muzeyyen Aslaner Ak
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Birsen Sahip
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ayfer Geduk
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Mehmer Ali Ucar
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Hacer Kale
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Tugba Hacibekiroglu
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Merve Gokcen Polat
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Yasin Kalpakci
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Ali Zahit Bolaman
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Birol Guvenc
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Sehmus Ertop
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Conceptualization: MAA, BS. Data curation: MAA, AG. Formal analysis: MGP, YK, HK. Investigation: MAA, TH. Methodology: MAA, MAU. Project administration: MAA, BS. Resources: MAA, MAU. Supervision: MAA, TH. Validation: AZB, BG, TH. Visualization: MAA, SE, MAU. Roles/Writing—original draft: MAA, AZB, BG. Writing—review & editing: SE, AZB, BG.

Corresponding author

Correspondence to Muzeyyen Aslaner Ak.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Consent to Participate

Written informed consent was obtained from each subject following a detailed explanation of the objectives and protocol of the study.

Consent for Publication

The permission was obtained from Zonguldak Bulent Ecevit University Clinical Research Ethics Committee for the use of patient data for publication purposes (Date of Approval: 15/04/2020; Reference Number/Protocol No: 2020/08).

Ethics Approval

This study was conducted in accordance with the ethical principles stated in the “Declaration of Helsinki” and approved by Zonguldak Bulent Ecevit University Clinical Research Ethics Committee (Date of Approval: 15/04/2020; Reference Number/Protocol No: 2020/08).

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary file1 (DOC 40 KB)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Ak, M.A., Sahip, B., Geduk, A. et al. The Clinical Efficacy of Epoetin Alfa and Darbepoetin Alfa in Patients with Low-Risk or Intermediate-1-Risk Myelodysplastic Syndrome: Retrospective Multi-center Real-Life Study. Indian J Hematol Blood Transfus 38, 299–308 (2022). https://doi.org/10.1007/s12288-021-01458-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12288-021-01458-1

Keywords

Search

Navigation