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CC BY-NC-ND 4.0 · South Asian J Cancer 2023; 12(04): 371-377
DOI: 10.1055/s-0042-1759785
Original Article
Hematological Malignancies

Experience with Generic Pegylated L-asparaginase in Children with Acute Lymphoblastic Leukemia from a Tertiary Care Oncology Center in South India

Dhaarani Jayaraman
1   Division of Pediatric Hemato-Oncology, Sri Ramachandra Institute of Higher Education and Research, Chennai, Tamil Nadu, India
,
Latha M. Sneha
1   Division of Pediatric Hemato-Oncology, Sri Ramachandra Institute of Higher Education and Research, Chennai, Tamil Nadu, India
,
Gracelin Jeyarani
1   Division of Pediatric Hemato-Oncology, Sri Ramachandra Institute of Higher Education and Research, Chennai, Tamil Nadu, India
,
Alekhya Somayajula 
2   Department of Pediatrics, Sri Ramachandra Institute of Higher Education and Research, Chennai, Tamil Nadu, India
,
Balaji Thiruvengadam Kothandam
1   Division of Pediatric Hemato-Oncology, Sri Ramachandra Institute of Higher Education and Research, Chennai, Tamil Nadu, India
,
Julius Xavier Scott
1   Division of Pediatric Hemato-Oncology, Sri Ramachandra Institute of Higher Education and Research, Chennai, Tamil Nadu, India
,
A Gadekar
3   Emcure Pharma, Pune, Maharashtra, India
› Author Affiliations Funding This project was funded by Emcure India Pvt. Ltd.
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Abstract

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Dhaarani Jayaraman

Background Acute lymphoblastic leukemia (ALL) is a common type of leukemia in children. The innovator pegylated L-asparaginase has several advantages over native L-asparaginase; however, its use in India is limited due to availability and cost. Therefore, a generic pegylated L-asparaginase can be considered as an alternative to the innovator molecule.

Methods A retrospective study was conducted to assess the outcome (minimal residual disease [MRD]) and toxicity of a generic pegylated L-asparaginase (Hamsyl) at the end of induction therapy.

Results Eighty-eight (80.7%) and 21 (19.3%) patients had received generic pegylated L-asparaginase and conventional asparaginase, respectively, as a part of their treatment protocol. Nearly 82% of patients had B-type ALL. Eight-one percent of children had a white blood cell count of fewer than 50,000/mm3. At the end of induction, 80.7% (88) of children were minimal residual disease (MRD)-negative, and at the end of augmented consolidation therapy, 20.2% were MRD-negative. Ten percent of patients exhibited allergic reactions. Two children had pancreatitis, and one child had central venous thrombosis.

Conclusion The generic pegylated L-asparaginase (Hamsyl) was effective and safe for use in pediatric ALL.

Keywords

acute lymphoblastic leukemia - L-asparaginase - generic pegylated L-asparaginase - pegaspargase - Hamsyl - hypersensitivity - minimal residual disease - MRD - ALL


Publication History

Article published online:
10 April 2023

© 2023. MedIntel Services Pvt Ltd. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/)

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  • References

  • 1 Ganguly S, Kinsey S, Bakhshi S. Childhood cancer in India. Cancer Epidemiol 2021; 71 (Pt B): 101679
    CrossrefPubMedGoogle Scholar
  • 2 Childhood Acute Lymphoblastic Leukemia Treatment. (PDQ®)–Health Professional Version - National Cancer Institute [Internet]. [cited 2021 Jun 21]. Accessed Nov 23, 2022, at: https://www.cancer.gov/types/leukemia/hp/child-all-treatment-pdq
    Google Scholar
  • 3 Asthana S, Labani S, Mehrana S, Bakhshi S. Incidence of childhood leukemia and lymphoma in India. Pediatr Hematol Oncol J 2018; 3 (04) 115-120
    CrossrefGoogle Scholar
  • 4 Arora RS, Arora B. Acute leukemia in children: a review of the current Indian data. South Asian J Cancer 2016; 5 (03) 155-160
    Article in Thieme ConnectPubMedGoogle Scholar
  • 5 Pui C-H, Yang JJ, Hunger SP. et al. Childhood acute lymphoblastic leukemia: progress through collaboration. J Clin Oncol 2015; 33 (27) 2938-2948
    CrossrefPubMedGoogle Scholar
  • 6 Kidd JG. Regression of transplanted lymphomas induced in vivo by means of normal guinea pig serum. I. Course of transplanted cancers of various kinds in mice and rats given guinea pig serum, horse serum, or rabbit serum. J Exp Med 1953; 98 (06) 565-582
    CrossrefPubMedGoogle Scholar
  • 7 Broome JD. Evidence that the L-asparaginase of guinea pig serum is responsible for its antilymphoma effects. I. Properties of the L-asparaginase of guinea pig serum in relation to those of the antilymphoma substance. J Exp Med 1963; 118 (01) 99-120
    CrossrefPubMedGoogle Scholar
  • 8 Heo YA, Syed YY, Keam SJ. Pegaspargase: A Review in Acute Lymphoblastic Leukaemia. Drugs 2019; 79 (07) 767-777
    CrossrefPubMedGoogle Scholar
  • 9 Egler RA, Ahuja SP, Matloub Y. L-asparaginase in the treatment of patients with acute lymphoblastic leukemia. J Pharmacol Pharmacother 2016; 7 (02) 62-71
    CrossrefPubMedGoogle Scholar
  • 10 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) 3874-3882
    CrossrefPubMedGoogle Scholar
  • 11 Shire Pharmaceuticals. Oncaspar (pegaspargase): US prescribing information. 2020 [Internet]. [cited 2021 Jun 21]. Accessed Nov 23, 2022, at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/193411s5196lbl.pdf
    PubMedGoogle Scholar
  • 12 European Medicines Agency. Oncaspar (pegaspargase): Summary of product characteristics. 2020 [Internet]. [cited 2021 Jun 21]. Accessed Nov 23, 2022, at: https://www.ema.europa.eu/en/documents/product-information/oncaspar-epar-product-information_en.pdf
    PubMedGoogle Scholar
  • 13 Nelson textbook of Pediatrics. Robert M. Kliegman, Joseph W. St Geme, Nathan J. Blum, Samir S. Shah, Robert C. Tasker, Karen M. Wilson; eds., emeritus Richard E. Behrman. Elsevier Inc., Philadelphia, PA,2019
  • 14 Jayaraman D, Uppuluri R, Swaminathan VV, Sivasankaran M, Patel S, Raj R. Affordable and safe health care for all children: lessons learned from the use of peg-asparaginase in a developing country. Indian J Med Paediatr Oncol 2017; 38 (03) 398-400
    Article in Thieme ConnectPubMedGoogle Scholar
  • 15 Nookala Krishnamurthy M, Narula G, Gandhi K. et al. Randomized, parallel group, open-label bioequivalence trial of intramuscular pegaspargase in patients with relapsed acute lymphoblastic leukemia. JCO Glob Oncol 2020; 6 (06) 1009-1016
    CrossrefPubMedGoogle Scholar
  • 16 Vyas C, Jain S, Kapoor G, Mehta A, Takkar Chugh P. Experience with generic pegylated L-asparaginase in children with acute lymphoblastic leukemia and monitoring of serum asparaginase activity. Pediatr Hematol Oncol 2018; 35 (5-6): 331-340
    CrossrefPubMedGoogle Scholar
  • 17 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 (06) 1986-1994
    CrossrefPubMedGoogle Scholar
  • 18 Kwok CS, Kham SK, Ariffin H, Lin HP, Quah TC, Yeoh AE. Minimal residual disease (MRD) measurement as a tool to compare the efficacy of chemotherapeutic drug regimens using Escherichia coli-asparaginase or Erwinia-asparaginase in childhood acute lymphoblastic leukemia (ALL). Pediatr Blood Cancer 2006; 47 (03) 299-304
    CrossrefPubMedGoogle Scholar
  • 19 Abuchowski A, Kazo GM, Verhoest Jr CR. et al. Cancer therapy with chemically modified enzymes. I. Antitumor properties of polyethylene glycol-asparaginase conjugates. Cancer Biochem Biophys 1984; 7 (02) 175-186
    PubMedGoogle Scholar
  • 20 Asselin BL, Whitin JC, Coppola DJ, Rupp IP, Sallan SE, Cohen HJ. Comparative pharmacokinetic studies of three asparaginase preparations. J Clin Oncol 1993; 11 (09) 1780-1786
    CrossrefPubMedGoogle Scholar
  • 21 Keating MJ, Holmes R, Lerner S, Ho DH. L-asparaginase and PEG asparaginase–past, present, and future. Leuk Lymphoma 1993; 10 (1, suppl) 153-157
    CrossrefPubMedGoogle Scholar
  • 22 Hijiya N, van der Sluis IM. Asparaginase-associated toxicity in children with acute lymphoblastic leukemia. Leuk Lymphoma 2016; 57 (04) 748-757
    CrossrefPubMedGoogle Scholar
  • 23 Wacker P, Land VJ, Camitta BM. et al; Children's Oncology Study Group. Allergic reactions to E. coli L-asparaginase do not affect outcome in childhood B-precursor acute lymphoblastic leukemia: a Children's Oncology Group Study. J Pediatr Hematol Oncol 2007; 29 (09) 627-632
    CrossrefPubMedGoogle Scholar
  • 24 Woo MH, Hak LJ, Storm MC. et al. Hypersensitivity or development of antibodies to asparaginase does not impact treatment outcome of childhood acute lymphoblastic leukemia. J Clin Oncol 2000; 18 (07) 1525-1532
    CrossrefPubMedGoogle Scholar
  • 25 Panosyan EH, Seibel NL, Martin-Aragon S. et al; Children's Cancer Group Study CCG-1961. Asparaginase antibody and asparaginase activity in children with higher-risk acute lymphoblastic leukemia: Children's Cancer Group Study CCG-1961. J Pediatr Hematol Oncol 2004; 26 (04) 217-226
    CrossrefPubMedGoogle Scholar
  • 26 Tong WH, Pieters R, Kaspers GJL. 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) 2026-2033
    CrossrefPubMedGoogle Scholar
  • 27 Boos J, Werber G, Ahlke E. et al. Monitoring of asparaginase activity and asparagine levels in children on different asparaginase preparations. Eur J Cancer 1996; 32A (09) 1544-1550
    CrossrefPubMedGoogle Scholar
  • 28 Pui CH, Burghen GA, Bowman WP, Aur RJA. Risk factors for hyperglycemia in children with leukemia receiving L-asparaginase and prednisone. J Pediatr 1981; 99 (01) 46-50
    CrossrefPubMedGoogle Scholar
  • 29 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) 2237-2253
    CrossrefPubMedGoogle Scholar
  • 30 Dinndorf PA, Gootenberg J, Cohen MH, Keegan P, Pazdur R. FDA drug approval summary: pegaspargase (oncaspar) for the first-line treatment of children with acute lymphoblastic leukemia (ALL). Oncologist 2007; 12 (08) 991-998
    CrossrefPubMedGoogle Scholar
  • 31 Raja RA, Schmiegelow K, Frandsen TL. Asparaginase-associated pancreatitis in children. Br J Haematol 2012; 159 (01) 18-27
    CrossrefPubMedGoogle Scholar
  • 32 Kearney SL, Dahlberg SE, Levy DE, Voss SD, Sallan SE, Silverman LB. Clinical course and outcome in children with acute lymphoblastic leukemia and asparaginase-associated pancreatitis. Pediatr Blood Cancer 2009; 53 (02) 162-167
    CrossrefPubMedGoogle Scholar
  • 33 Kamat A. Retrospective post-marketing study on the use of bio-similar pegasparagase among acute lymphoblastic leukemia patients in India. Pediatr Hematol Oncol J 2018; 3 (01) 9-12
    CrossrefGoogle Scholar
  • 34 Payne JH, Vora AJ. Thrombosis and acute lymphoblastic leukaemia. Br J Haematol 2007; 138 (04) 430-445
    CrossrefPubMedGoogle Scholar
  • 35 Hourani R, Abboud M, Hourani M, Khalifeh H, Muwakkit S. L-asparaginase-induced posterior reversible encephalopathy syndrome during acute lymphoblastic leukemia treatment in children. Neuropediatrics 2008; 39 (01) 46-50
    Article in Thieme ConnectPubMedGoogle Scholar
  • 36 Merryman R, Stevenson KE, Gostic II WJ. et al. Asparaginase-associated myelosuppression and effects on dosing of other chemotherapeutic agents in childhood acute lymphoblastic leukemia. Pediatr Blood Cancer 2012; 59 (05) 925-927
    CrossrefPubMedGoogle Scholar
  • 37 Parsons SK, Skapek SX, Neufeld EJ. et al. Asparaginase-associated lipid abnormalities in children with acute lymphoblastic leukemia. Blood 1997; 89 (06) 1886-1895
    CrossrefPubMedGoogle Scholar
  • 38 Verma A, Chen K, Bender C, Gorney N, Leonard W, Barnette P. PEGylated E. coli asparaginase desensitization: an effective and feasible option for pediatric patients with acute lymphoblastic leukemia who have developed hypersensitivity to pegaspargase in the absence of asparaginase Erwinia chrysanthemi availability. Pediatr Hematol Oncol 2019; 36 (05) 277-286
    CrossrefPubMedGoogle Scholar
  • 39 Vrooman LM, Stevenson KE, Supko JG. et al. Postinduction dexamethasone and individualized dosing of Escherichia Coli L-asparaginase each improve outcome of children and adolescents with newly diagnosed acute lymphoblastic leukemia: results from a randomized study–Dana-Farber Cancer Institute ALL Consortium Protocol 00-01. J Clin Oncol 2013; 31 (09) 1202-1210
    CrossrefPubMedGoogle Scholar
  • 40 Hu X, Wildman KP, Basu S, Lin PL, Rowntree C, Saha V. The cost-effectiveness of pegaspargase versus native asparaginase for first-line treatment of acute lymphoblastic leukaemia: a UK-based cost-utility analysis. Health Econ Rev 2019; 9 (01) 40
    CrossrefPubMedGoogle Scholar
  • 41 NICE. Pegaspargase-for-treating-acute-lymphoblastic-leukaemia-pdf-82604549478085.pdf [Internet]. [cited 2021 Jun 21]. Accessed Nov 23, 2022, at: https://www.nice.org.uk/guidance/ta408/resources/pegaspargase-for-treating-acute-lymphoblastic-leukaemia-pdf-82604549478085
    Google Scholar