Subscribe to RSS
DOI: 10.1055/s-0042-1759785
Experience with Generic Pegylated L-asparaginase in Children with Acute Lymphoblastic Leukemia from a Tertiary Care Oncology Center in South India
Funding This project was funded by Emcure India Pvt. Ltd.Abstract
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 - ALLPublication 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/)
Thieme Medical and Scientific Publishers Pvt. Ltd.
A-12, 2nd Floor, Sector 2, Noida-201301 UP, India
-
References
- 1 Ganguly S, Kinsey S, Bakhshi S. Childhood cancer in India. Cancer Epidemiol 2021; 71 (Pt B): 101679
- 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
- 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
- 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
- 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
- 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
- 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
- 8 Heo YA, Syed YY, Keam SJ. Pegaspargase: A Review in Acute Lymphoblastic Leukaemia. Drugs 2019; 79 (07) 767-777
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 22 Hijiya N, van der Sluis IM. Asparaginase-associated toxicity in children with acute lymphoblastic leukemia. Leuk Lymphoma 2016; 57 (04) 748-757
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 31 Raja RA, Schmiegelow K, Frandsen TL. Asparaginase-associated pancreatitis in children. Br J Haematol 2012; 159 (01) 18-27
- 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
- 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
- 34 Payne JH, Vora AJ. Thrombosis and acute lymphoblastic leukaemia. Br J Haematol 2007; 138 (04) 430-445
- 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
- 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
- 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
- 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
- 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
- 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
- 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