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Drugs

, Volume 79, Issue 7, pp 767–777 | Cite as

Pegaspargase: A Review in Acute Lymphoblastic Leukaemia

  • Young-A. HeoEmail author
  • Yahiya Y. Syed
  • Susan J. Keam
Adis Drug Evaluation

Abstract

Pegaspargase (Oncaspar®), a pegylated form of native Escherichia coli-derived l-asparaginase (hereafter referred as E. colil-asparaginase), is indicated in the USA and EU for the treatment of acute lymphoblastic leukaemia (ALL) as a component of multi-agent chemotherapy in paediatric and adult patients. Relative to E. colil-asparaginase, pegaspargase has a prolonged circulation time, thereby offering less frequent administration. Moreover, pegylation of E. colil-asparaginase may diminish the immunogenicity of the enzyme. Based on extensive evidence, intramuscular (IM) or intravenous (IV) administration of pegaspargase as a component of a multi-agent chemotherapy is an effective first-line treatment for paediatric and adult patients with ALL, as well as for the treatment of paediatric and adult patients with ALL and hypersensitivity to E. colil-asparaginase. Pegaspargase had a manageable tolerability profile in paediatric and adult patients with newly diagnosed ALL, with the most commonly occurring adverse events being generally consistent to that seen with E. colil-asparaginase. Pegaspargase treatment in patients with relapsed ALL and hypersensitivity to E. colil-asparaginase had a similar tolerability profile to that observed in patients with newly diagnosed ALL. Given the potentially reduced immunogenicity and more convenient dosage regimen over E. colil-asparaginase, pegaspargase remains an important and effective treatment option for paediatric and adult patients with ALL, including those with hypersensitivity to E. colil-asparaginase.

Notes

Acknowledgements

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

Compliance with Ethical Standards

Funding

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

Conflicts of interest

Young-A Heo, Yahiya Syed and Susan Keam are salaried employees of Adis/Springer, are responsible for the article content and declare no relevant conflicts of interest.

Supplementary material

40265_2019_1120_MOESM1_ESM.docx (19 kb)
Supplementary material 1 (DOCX 19 kb)

References

  1. 1.
    National Comprehensive Cancer Network. Acute lymphoblastic leukemia (NCCN clinical practice guidelines in oncology). 2018. http://www.nccn.org/. Accessed 4 Mar 2019.
  2. 2.
    Hoelzer D, Bassan R, Dombret H, et al. Acute lymphoblastic leukaemia in adult patients: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2016;27(Suppl 5):v69–82.Google Scholar
  3. 3.
    Asselin BL. The three asparaginases: comparative pharmacology and optimal use in childhood leukemia. In: Kaspers GJL, Pieters R, Veerman AJP, editors. Drug resistance in leukemia and lymphoma III Advances in experimental medicine and biology. Boston: Springer; 1999. p. 621–9.Google Scholar
  4. 4.
    Pui CH, Evans WE. Treatment of acute lymphoblastic leukemia. N Engl J Med. 2006;354(2):166–78.CrossRefGoogle Scholar
  5. 5.
    Silverman LB, Supko JG, Stevenson KE, et al. Intravenous PEG-asparaginase during remission induction in children and adolescents with newly diagnosed acute lymphoblastic leukemia. Blood. 2010;115(7):1351–3.CrossRefGoogle Scholar
  6. 6.
    Tong WH, Pieters R, Kaspers GJ, et al. A prospective study on drug monitoring of PEGasparaginase and Erwinia asparaginase and asparaginase antibodies in pediatric acute lymphoblastic leukemia. Blood. 2014;123(13):2026–33.CrossRefGoogle Scholar
  7. 7.
    Pisal DS, Kosloski MP, Balu-Iyer SV. Delivery of therapeutic proteins. J Pharm Sci. 2010;99(6):2557–75.CrossRefGoogle Scholar
  8. 8.
    Shire Pharmaceuticals. Oncaspar (pegaspargase): US prescribing information. 2019. http://www.fda.gov. Accessed 9 Apr 2019.
  9. 9.
    European Medicines Agency. Oncaspar (pegaspargase): summary of product characteristics. 2018. http://www.ema.europa.eu/. Accessed 9 Apr 2019.
  10. 10.
    Servier Pharmaceuticals. ASPARLAS™ (calaspargase pegol—mknl): US prescribing information. 2018. http://www.fda.gov. Accessed 9 Apr 2019.
  11. 11.
    Avramis VI, Sencer S, Periclou AP, et al. A randomized comparison of native Escherichia coli asparaginase and polyethylene glycol conjugated asparaginase for treatment of children with newly diagnosed standard-risk acute lymphoblastic leukemia: a children’s cancer group study. Blood. 2002;99(6):1986–94.CrossRefGoogle Scholar
  12. 12.
    Place AE, Stevenson KE, Vrooman LM, et al. Intravenous pegylated asparaginase versus intramuscular native Escherichia coli l-asparaginase in newly diagnosed childhood acute lymphoblastic leukaemia (DFCI 05-001): a randomised, open-label phase 3 trial. Lancet Oncol. 2015;16(16):1677–90.CrossRefGoogle Scholar
  13. 13.
    European Medicines Agency. EPAR assessment report: oncaspar 2016. http://www.ema.europa.eu. Accessed 9 Apr 2019.
  14. 14.
    Wurthwein G, Lanvers-Kaminsky C, Hempel G, et al. Population pharmacokinetics to model the time-varying clearance of the pegylated asparaginase Oncaspar(R) in children with acute lymphoblastic leukemia. Eur J Drug Metab Pharmacokinet. 2017;42(6):955–63.CrossRefGoogle Scholar
  15. 15.
    Angiolillo AL, Schore RJ, Devidas M, et al. Pharmacokinetic and pharmacodynamic properties of calaspargase pegol Escherichia coli l-asparaginase in the treatment of patients with acute lymphoblastic leukemia: results from children’s oncology group study AALL07P4. J Clin Oncol. 2014;32(34):3874–82.CrossRefGoogle Scholar
  16. 16.
    DeAngelo DJ, Stevenson K, Neuberg DS, et al. A multicenter phase II study using a dose intensified pegylated-asparaginase pediatric regimen in adults with untreated acute lymphoblastic leukemia: a DFCI ALL consortium trial [abstract]. Blood. 2015;126(23):80.Google Scholar
  17. 17.
    Dinndorf PA, Gootenberg J, Cohen MH, et al. FDA drug approval summary: pegaspargase (Oncaspar®) for the first-line treatment of children with acute lymphoblastic leukemia (ALL). Oncologist. 2007;12(8):991–8.CrossRefGoogle Scholar
  18. 18.
    Douer D, Aldoss I, Lunning MA, et al. Pharmacokinetics-based integration of multiple doses of intravenous pegaspargase in a pediatric regimen for adults with newly diagnosed acute lymphoblastic leukemia. J Clin Oncol. 2014;32(9):905–11.CrossRefGoogle Scholar
  19. 19.
    Liang J, Shi P, Guo X, et al. A retrospective comparison of Escherichia coli and polyethylene glycol-conjugated asparaginase for the treatment of adolescents and adults with newly diagnosed acute lymphoblastic leukemia. Oncol Lett. 2018;15(1):75–82.Google Scholar
  20. 20.
    Gökbuget N, Beck J, Brandt K, et al. Significant improvement of outcome in adolescents and young adults (AYAs) aged 15-35 years with acute lymphoblastic leukemia (ALL) with a pediatric derived adult ALL protocol; results of 1529 AYAs in 2 consecutive trials of the german multicenter study group for adult ALL (GMALL) [abstract]. Blood. 2013;122(21):839.Google Scholar
  21. 21.
    Rytting ME, Jabbour EJ, Jorgensen JL, et al. Final results of a single institution experience with a pediatric-based regimen, the augmented Berlin-Frankfurt-Munster, in adolescents and young adults with acute lymphoblastic leukemia, and comparison to the hyper-CVAD regimen. Am J Hematol. 2016;91(8):819–23.CrossRefGoogle Scholar
  22. 22.
    Ribera JM, Morgades M, Montesinos P, et al. Efficacy and safety of native versus pegylated Escherichia coli asparaginase for treatment of adults with high-risk, philadelphia chromosome-negative acute lymphoblastic leukemia. Leuk Lymphoma. 2018;59(7):1634–43.CrossRefGoogle Scholar
  23. 23.
    Stock W, Luger SM, Advani AS, et al. A pediatric regimen for older adolescents and young adults with acute lymphoblastic leukemia: results of CALGB 10403. Blood. 2019;133(14):1548–59.CrossRefGoogle Scholar
  24. 24.
    Wetzler M, Sanford BL, Kurtzberg J, et al. Effective asparagine depletion with pegylated asparaginase results in improved outcomes in adult acute lymphoblastic leukemia: cancer and leukemia group B Study 9511. Blood. 2007;109(10):4164–7.CrossRefGoogle Scholar
  25. 25.
    Therapeutic Goods Administration. Extract from the clinical evaluation report for pegaspargase. 2017. http://www.tga.gov.au/. Accessed 9 Apr 2019.
  26. 26.
    Kurtzberg J, Asselin B, Bernstein M, et al. Polyethylene glycol-conjugated l-asparaginase versus native l-asparaginase in combination with standard agents for children with acute lymphoblastic leukemia in second bone marrow relapse: a children’s oncology group study (POG 8866). J Pediatr Hematol Oncol. 2011;33(8):610–6.CrossRefGoogle Scholar
  27. 27.
    Stock W, Douer D, DeAngelo DJ, et al. Prevention and management of asparaginase/pegasparaginase-associated toxicities in adults and older adolescents: recommendations of an expert panel. Leuk Lymphoma. 2011;52(12):2237–53.CrossRefGoogle Scholar
  28. 28.
    De Abrew KG, Richardson DS, Cook MA, et al. Hepatotoxicity with pegylated-asparaginase in acute lymphoblastic leukaemia is influenced by raised body mass index [abstract no. 249]. Br J Haematol. 2016;173 (Suppl 1):103.Google Scholar
  29. 29.
    Hasan H, Shaikh OM, Rassekh SR, et al. Comparison of hypersensitivity rates to intravenous and intramuscular PEG-asparaginase in children with acute lymphoblastic leukemia: a meta-analysis and systematic review. Pediatr Blood Cancer. 2017;64(1):81–8.CrossRefGoogle Scholar
  30. 30.
    MacDonald T, Kulkarni K, Bernstein M, et al. Allergic reactions with intravenous compared with intramuscular pegaspargase in children with high-risk acute lymphoblastic leukemia: a population-based study from the maritimes, Canada. J Pediatr Hematol Oncol. 2016;38(5):341–4.CrossRefGoogle Scholar
  31. 31.
    Abbott LS, Zakova M, Shaikh F, et al. Allergic reactions associated with intravenous versus intramuscular pegaspargase: a retrospective chart review. Paediatr Drugs. 2015;17(4):315–21.CrossRefGoogle Scholar
  32. 32.
    Burke MJ, Devidas M, Maloney K, et al. Severe pegaspargase hypersensitivity reaction rates (grade ≥ 3) with intravenous infusion vs. intramuscular injection: analysis of 54,280 doses administered to 16,534 patients on children’s oncology group (COG) clinical trials. Leuk Lymphoma. 2018;59(7):1624–33.Google Scholar
  33. 33.
    National Institue for Health and Care Excellence. Technology appraisal guidance: pegaspargase for treating acute lymphoblastic leukaemia. 2016. http://www.nice.org.uk. Accessed 9 Apr 2019.
  34. 34.
    van der Sluis IM, Vrooman LM, Pieters R, et al. Consensus expert recommendations for identification and management of asparaginase hypersensitivity and silent inactivation. Haematologica. 2016;101(3):279–85.CrossRefGoogle Scholar
  35. 35.
    Basu S, Lin PL, Saha V. The cost-effectiveness of pegaspargase for first-line treatment of acute lymphoblastic leukaemia: a cost-utility analysis. [abstract no. PCN180]. Value Health. 2017;20 (9):A444.Google Scholar
  36. 36.
    Delattre C, Lecureuil C, Staginnus U, et al. Cost-minimization analysis of pegaspargase and native E. Coli asparaginase to treat children and adults with acute lymphoblastic leukemia in Belgium. [abstract no. PSY86]. Value Health. 2016;19(7):A590.Google Scholar
  37. 37.
    Faiella M, Lecureuil C, Staginnus U, et al. Pegaspargase in the treatment of Acute Lymphoblastic Leukemia: A CMA model demonstrates its economic benefit for the Italian National Health System. [abstract no. PSY87]. Value Health. 2016;19 (7):A590.Google Scholar
  38. 38.
    Lecureuil C, Staginnus U, Robbins S, et al. Pegaspargase versus asparaginase in childhood acutely lymphoblastic leukemia: a cost-minimization analysis in France. [abstract no. PSY84]. Value Health. 2016;19(7):A589–A90.Google Scholar
  39. 39.
    Villoro R, Aisa F, Domenech M, et al. Pharmacoeconomic assessment of pegaspargase versus asparaginase in acute lymphocytic leukemia. [abstract no. PCN169]. Value Health. 2016;19 (7):A739.Google Scholar
  40. 40.
    US National Institutes of Health. ClinicalTrials.gov [identifier NCT01574274]. 2018.http://www.clinicaltrials.gov/. Accessed 9 Apr 2019.
  41. 41.
    US National Institutes of Health. ClinicalTrials.gov [identifier NCT00671034]. 2018.http://www.clinicaltrials.gov/. Accessed 9 Apr 2019.

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.SpringerAucklandNew Zealand

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