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Comparison of transplant outcomes and economic costs between biosimilar and originator filgrastim in allogeneic hematopoietic stem cell transplantation

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Abstract

From January 2012 to September 2015, 49 patients received biosimilar filgrastim (BF) after allogeneic bone marrow transplantation (BMT, n = 31) or peripheral stem cell transplantation (PBSCT, n = 18) in our institution. To evaluate the clinical impact of BF on transplant outcomes of these patients, we compared hematological recovery, overall survival (OS), disease-free survival (DFS), transplantation-related mortality (TRM), cumulative incidence of relapse (CIR), and acute and chronic graft-versus-host disease (GVHD) with those of control patients who received originator filgrastim (OF) after BMT (n = 31) or PBSCT (n = 18). All cases were randomly selected from a clinical database in our institution. In both the BMT and PBSCT settings, neutrophil recovery (17 vs. 19 days in BMT; 13 vs. 15 days in PBSCT) and platelet recovery (27 vs. 31 days in BMT; 17 vs. 28 days in PBSCT) were essentially the same between BF and OF. They were also comparable in terms of OS, DFS, TRM, CIR, and the incidence of acute GVHD and chronic GVHD. On multivariate analysis, the use of BF in both BMT and PBSCT was not a significant factor for adverse transplant outcomes. Although BF significantly reduced filgrastim costs in both BMT and PBSCT, total hospitalization costs were not significantly different between BF and OF.

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References

  1. Sörgel F, Schwebig A, Holzmann J, Prasch S, Singh P, Kinzig M. Comparability of biosimilar filgrastim with originator filgrastim: protein characterization, pharmacodynamics, and pharmacokinetics. BioDrugs. 2015;29:123–31.

    Article  PubMed  PubMed Central  Google Scholar 

  2. Welte K. G-CSF: filgrastim, lenograstim and biosimilars. Expert Opin Biol Ther. 2014;14:983–93.

    Article  CAS  PubMed  Google Scholar 

  3. Blackwell K, Semiglazov V, Krasnozhon D, Davidenko I, Nelyubina L, Nakov R, et al. Comparison of EP2006, a filgrastim biosimilar, to the reference: a phase III, randomized, double-blind clinical study in the prevention of severe neutropenia in patients with breast cancer receiving myelosuppressive chemotherapy. Ann Oncol. 2015;26:1948–53.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Nahon S, Rastkhah M, Ben Abdelghani M, Soumoudronga RF, Gasnereau I, Labourey JL. Zarzio®, biosimilar of filgrastim, in prophylaxis of chemotherapy-induced neutropenia in routine practice: a French prospective multicentric study. Support Care Cancer. 2015. (Epub ahead of print).

  5. Uddin S, Russell P, Farrell M, Davy B, Taylor J, Agrawal SG. Use of biosimilar filgrastim compared with lenograstim in autologous haematopoietic stem-cell transplant and in sibling allogeneic transplant. Ther Adv Hematol. 2015;6:53–60.

    Article  PubMed  PubMed Central  Google Scholar 

  6. Marchesi F, Cerchiara E, Dessanti ML, Gumenyuk S, Franceschini L, Palombi F, et al. Comparison between biosimilar filgrastim vs other granulocyte-colony stimulating factor formulations (originator filgrastim, peg-filgrastim and lenograstim) after autologous stem cell transplantation: a retrospective survey from the Rome Transplant Network. Br J Haematol. 2015;169:293–6.

    Article  CAS  PubMed  Google Scholar 

  7. Lanotto JC, Ngo Sack F, Couturier MA, Tempescul A, Mugnier N, Delepine P, et al. Biosimilars of filgrastim in autologous stem cell transplant: reduction in granulocyte-colony stimulating factor costs, but similar effects on bone marrow recovery. Leuk Lymphoma. 2014;55:74–7.

    Article  Google Scholar 

  8. Marchesi F, Vacca M, Gumenyuk S, Pandolfi A, Renzi D, Palombi F, et al. Biosimilar filgrastim (Zarzio®) vs. lenograstim (Myelostim®) for peripheral blood stem cell mobilization in adult patients with lymphoma and myeloma: a single center experience. Leuk Lymphoma. 2015:1–4 (Epub ahead of print).

  9. Schmitt M, Publicover A, Orchard KH, Görlach M, Wang L, Schmitt A, et al. Biosimilar G-CSF based mobilization of peripheral blood hematopoietic stem cells for autologous and allogeneic stem cell transplantation. Theranostics. 2014;4:280–9.

    Article  PubMed  PubMed Central  Google Scholar 

  10. Danylesko I, Sareli R, Bloom-Varda N, Yerushalmi R, Shem-Tov N, Shimoni A, et al. Biosimilar Filgrastim (Tevagrastim, XMO2) for allogeneic hematopoietic stem cell mobilization and transplantation in patients with acute myelogenous leukemia/myelodysplastic syndromes. Biol Blood Marrow Transplant. 2016;22:277–83.

    Article  CAS  PubMed  Google Scholar 

  11. Martin PJ, Lee SJ, Przepiorka D, Horowitz MM, Koreth J, Vogelsang GB, et al. National Institutes of Health Consensus Development Project on Criteria for Clinical Trials in Chronic Graft-versus-Host Disease: VI. The 2014 Clinical Trial Design Working Group Report. Biol Blood Marrow Transplant. 2015;21:1343–59.

    Article  PubMed  PubMed Central  Google Scholar 

  12. Przepiorka D, Weisdorf D, Martin P, Klingemann HG, Beatty P, Hows J, et al. 1994 consensus conference on acute GVHD grading. Bone Marrow Transplant. 1995;15:825–8.

    CAS  PubMed  Google Scholar 

  13. Martino M, Recchia AG, Moscato T, Fedele R, Neri S, Gentile M, et al. Efficacy of biosimilar granulocyte colony-stimulating factor versus originator granulocyte colony-stimulating factor in peripheral blood stem cell mobilization in de novo multiple myeloma patients. Cytotherapy. 2015;17:1485–93.

    Article  CAS  PubMed  Google Scholar 

  14. Mattii L, Battolla B, Azzarà A, D’Urso G, Montali U, Petrini M. Glycosylation interference on RhoA activation: focus on G-CSF. Leuk Res. 2011;35:265–7.

    Article  CAS  PubMed  Google Scholar 

  15. McQuaker IG, Hunter AE, Pacey S, Haynes AP, Iqbal A, Russell NH. Low-dose filgrastim significantly enhances neutrophil recovery following autologous peripheral-blood stem-cell transplantation in patients with lymphoproliferative disorders: evidence for clinical and economic benefit. J Clin Oncol. 1997;2:451–7.

    Google Scholar 

  16. Ringdén O, Labopin M, Gorin NC, Le Blanc K, Rocha V, Gluckman E, et al. Treatment with granulocyte colony-stimulating factor after allogeneic bone marrow transplantation for acute leukemia increases the risk of graft-versus-host disease and death: a study from the Acute Leukemia Working Party of the European Group for Blood and Marrow Transplantation. J Clin Oncol. 2004;22:416–23.

    Article  PubMed  Google Scholar 

  17. Khoury HJ, Loberiza FR Jr, Ringdén O, Barrett AJ, Bolwell BJ, Cahn JY, Champlin RE, Gale RP, Hale GA, Urbano-Ispizua A, Martino R, McCarthy PL, Tiberghien P, Verdonck LF, Horowitz MM. Impact of posttransplantation G-CSF on outcomes of allogeneic hematopoietic stem cell transplantation. Blood. 2006;107:1712–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Dekker A, Bulley S, Beyene J, Dupuis LL, Doyle JJ, Sung L. Meta-analysis of randomized controlled trials of prophylactic granulocyte colony-stimulating factor and granulocyte-macrophage colony-stimulating factor after autologous and allogeneic stem cell transplantation. J Clin Oncol. 2006;33:5207–15.

    Article  Google Scholar 

  19. Ho VT, Mirza NQ, Junco DD, Okamura T, Przepiorka D. The effect of hematopoietic growth factors on the risk of graft-vs-host disease after allogeneic hematopoietic stem cell transplantation: a meta-analysis. Bone Marrow Transplant. 2003;32:771–5.

    Article  CAS  PubMed  Google Scholar 

  20. Trigg ME, Peters C, Zimmerman MB. Administration of recombinant human granulocyte-macrophage colony-stimulating factor to children undergoing allogeneic marrow transplantation: a prospective, randomized, double-masked, placebo-controlled trial. Pediatr Transplant. 2000;4:123–31.

    Article  CAS  PubMed  Google Scholar 

  21. Yanada M. Allogeneic hematopoietic cell transplantation for acute myeloid leukemia during first complete remission: a clinical perspective. Int J Hematol. 2015;101:243–54.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

The authors would like to thank the nursing staff at Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, for their assistance in the collection of samples from the patients included in this study.

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Authors and Affiliations

  1. Hematology Division, Tokyo Metropolitan Cancer and Infectious Disease Center, Komagome Hospital, 3-18-22 Honkomagome, Bunkyo-ku, Tokyo, 113-8677, Japan

    Kaito Harada, Yuta Yamada, Tatsuya Konishi, Akihito Nagata, Toshiaki Takezaki, Satoshi Kaito, Shuhei Kurosawa, Masahiro Sakaguchi, Shunichiro Yasuda, Kosuke Yoshioka, Kyoko Watakabe-Inamoto, Aiko Igarashi, Yuho Najima, Takeshi Hagino, Hideharu Muto, Takeshi Kobayashi, Noriko Doki, Kazuhiko Kakihana, Hisashi Sakamaki & Kazuteru Ohashi

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  1. Kaito Harada
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  2. Yuta Yamada
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  3. Tatsuya Konishi
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  4. Akihito Nagata
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  7. Shuhei Kurosawa
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  12. Aiko Igarashi
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  14. Takeshi Hagino
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  15. Hideharu Muto
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  16. Takeshi Kobayashi
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  17. Noriko Doki
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  18. Kazuhiko Kakihana
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  19. Hisashi Sakamaki
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  20. Kazuteru Ohashi
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Corresponding author

Correspondence to Kazuteru Ohashi.

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Conflict of interest

There are no competing financial interests.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. The study was approved by the ethics committee of Tokyo Metropolitan Cancer and Infectious Disease Center, Komagome Hospital (Tokyo, Japan), where this study was organized.

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Harada, K., Yamada, Y., Konishi, T. et al. Comparison of transplant outcomes and economic costs between biosimilar and originator filgrastim in allogeneic hematopoietic stem cell transplantation. Int J Hematol 104, 709–719 (2016). https://doi.org/10.1007/s12185-016-2085-0

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  • DOI: https://doi.org/10.1007/s12185-016-2085-0

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