Evaluation of the efficacy and safety of pegaspargase, compared to L-asparaginase, and its economic viability in the treatment of acute lymphoblastic leucemia
Série temática: Avaliação de Tecnologias em Saúde Hospitalar (ATS-H)
DOI:
https://doi.org/10.34019/1982-8047.2023.v49.43248Keywords:
Precursor cell lymphoblastic leukemia-lymphoma, Asparaginase, Evaluation of the efficacy-effectiveness of interventions, Drug-related side effects and adverse reactions, Health evaluationAbstract
Introduction: Treatment of acute lymphoblastic leukemia (ALL) is associated with adverse events (AEs) and mortality due to toxicity of the drugs used. Protocols with L-asparaginase (L-Asp) have shown improved prognosis, but can cause hypersensitivity and development of neutralizing antibodies, as L-Asp is produced from Escherichia coli. The conjugation of E. coli L-Asp with monomethoxypolyethylene glycol (PEG) results in PEG-Asp, with lower immunogenicity and longer half-life. Objective: to evaluate the efficacy and safety of PEG-Asp, compared to L-Asp, in the treatment of ALL, and its economic viability in order to subsidize the decision making regarding its incorporation. Methods: Evidence was searched in MEDLINE, Cochrane Library, Embase and Epistemonikos, and on websites of HTA agencies. Systematic reviews, clinical trials and observational studies published in English, Spanish and Portuguese, regardless of date, were considered eligible. Economic viability was calculated based on the cost of using PEG-Asp in the GRAALL - 2003 protocol compared to the amount billed via APAC. Results: Evidence showed similar efficacy between PEG-Asp and L-Asp for most of the outcomes of interest, with superiority in prevention of CNS leukemia in adults and in dosage convenience. PEG-Asp showed a higher frequency of AEs in newly diagnosed adults, and no difference in toxicity and mortality in relapsed adults. The incorporation of PEG-Asp proved to be economically viable for adult patients, and disadvantageous for patients between 18 and 19 years of age, considering a mean body surface area of 1.7 m2. Conclusion: The incorporation of PEG-Asp for the treatment of ALL in patients over 18 years of age was recommended, and in those aged 18 to 19 years incomplete, the economic viability should be assessed according to body surface area. In addition to the efficacy and safety profile of PEG-Asp, there are no drugs in this therapeutic class for adults registered within ANVISA.
Downloads
References
Heo Young-A, Syed YY, Keam SJ. Pegaspargase: a review in acute lymphoblastic leukaemia. Drugs. 2019; 79(7):767-77.
National Cancer Institute. Adult acute lymphoblastic leukemia treatment (PDQ®): health professional version [Internet]. 2019 [citado em 2024 jan. 3]. Disponível em: https://www.cancer.gov/types/leukemia/hp/adult-all-treatment-pdq
Bade NA, Lu C, Patzke CL, Baer MR, Duong VH, Law JY et al. Optimizing pegylated asparaginase use: an institutional guideline for dosing, monitoring, and management. Journal of Oncology Pharmacy Practice. 2020; 26(1):74-92.
Rytting M. Peg-asparaginase for acute lymphoblastic leukemia. Expert Opinion on Biological Therapy. 2010; 10(5):833-9.
Hoelzer D, Bassan R, Dombret H, Fielding A, Ribera JM, Buske C. Acute lymphoblastic leukaemia in adult patients: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Annals of Oncology. 2016; 27:v69-82.
Aldoss I, Douer D. How I treat the toxicities of pegasparaginase in adults with acute lymphoblastic leukemia. Blood. 2020; 135(13):987-995.
Kurtzberg J, Asselin B, Bernstein M, Buchanan GR, Pollock BH, Camitta BM. 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. Journal of Pediatric Hematology/Oncology. 2011; 33(8):610-6.
Daley RJ, Rajeeve S, Kabel CC, Pappacena JJ, Stump SE, Lavery JA et al. Tolerability and toxicity of pegaspargase in adults 40 years and older with acute lymphoblastic leukemia. Leukemia & Lymphoma. 2021; 62(1):176-84.
Oparaji JA, Rose F, Okafor D, Howard A, Turner RL, Orabi AI et al. Risk factors for asparaginase-associated pancreatitis: a systematic review. Journal of Clinical Gastroenterology. 2017; 51(10):907-13.
Dai ZJ, Huang YQ, Lu Y. Efficacy and safety of PEG-asparaginase versus E. coli L-asparaginase in Chinese children with acute lymphoblastic leukemia: a meta-analysis. Translational Pediatrics. 2021; 10(2):244-55.
Liu W, Wang H, Wang W, Zhu M, Liu C, Wang J et al. Use of PEG-asparaginase in newly diagnosed adults with standard-risk acute lymphoblastic leukemia compared with E. coli-asparaginase: a retrospective single-center study. Scientific Reports. 2016; 6(1).
Medawar CV, Mosegui GBG, Vianna CMM, Costa TMA. PEG-asparaginase and native Escherichia coli L-asparaginase in acute lymphoblastic leukemia in children and adolescents: a systematic review. Hematology, Transfusion and Cell Therapy. 2020; 42(1):54-61.
Place AE, Stevenson KE, Vrooman LM, Harris MH, Hunt SK, O’Brien JE 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. The Lancet Oncology. 2015; 16(16):1677-90.
Ribera J, Morgades M, Montesinos P, Martino R, Barba P, Yolanda B 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. Leukemia & Lymphoma. 2018; 59(7):1634-43.
Faderl S, Thomas DA, O’Brien S, Ravandi F, Garcia-Manero G, Borthakur G et al. Augmented hyper-CVAD based on dose-intensified vincristine, dexamethasone, and asparaginase in adult acute lymphoblastic leukemia salvage therapy. Clinical Lymphoma Myeloma and Leukemia. 2011; 11(1):54-9.
Avramis VI, Sencer S, Periclou AP, Sather H, Bostrom BC, Cohen LJ 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.
Hak LJ, Relling MV, Cheng C, Pei D, Wang B, Sandlund JT et al. Asparaginase pharmacodynamics differ by formulation among children with newly diagnosed acute lymphoblastic leukemia. Leukemia. 2004; 18(6):1072-7.
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):331-40.
Rozen L, Noubouossie D, Dedeken L, Huybrechts S, Lê PQ, Ferster A et al. Different profile of thrombin generation in children with acute lymphoblastic leukaemia treated with native or pegylated asparaginase: a cohort study. Pediatr Blood Cancer. 2017; 64(2):294-301.
Lowas SR, Marks D, Malempati S. Prevalence of transient hyperglycemia during induction chemotherapy for pediatric acute lymphoblastic leukemia. Pediatr Blood Cancer. 2009; 52(7):814-8.
Liang J, Shi P, Guo X, Li J, He L, Wang Y 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.
National Institute for Health and Care Excellence. Pegaspargase for treating acute lymphoblastic leukaemia-technology appraisal guidance [Internet]. 2016 [citado em 2024 jan. 3]. Disponível em: https://www.nice.org.uk/guidance/ta408.
Fu CH, Sakamoto KM. PEG-asparaginase. Expert Opin Pharmacother. 2007; 8(12):1977-84.
Electronic Medicines Compendium. Oncaspar 750 U/ml powder for solution for injection/infusion: summary of product characteristics (SmPC) (EMC) [Internet]. 2023 [citado em 2024 jan. 3]. Disponível em: https://www.medicines.org.uk/emc/product/10824/smpc#about-medicine.
European Medicines Agency. Oncaspar: EMA [Internet]. 2016 [citado em 2024 jan. 3]. Disponível em: https://www.ema.europa.eu/en/medicines/human/EPAR/oncaspar#ema-inpage-item-product-info.
Brasil. Agência Nacional de Vigilância Sanitária. Consulta produtos regularizados [Internet]. 2023 [citado em 2024 jan. 3]. Disponível em: https://consultas.anvisa.gov.br/#/medicamentos/25351771428201819/?substancia=7355.
Laboratórios Bagó do Brasil S.A. Spectrila®: asparaginase pó liofilizado para solução injetável 10.000 U por frasco: bula do profissional [Internet]. 2021 [citado em 2024 jan. 3]. Disponível em: https://consultas.anvisa.gov.br/api/consulta/medicamentos/arquivo/bula/parecer/eyJhbGciOiJIUzUxMiJ9.eyJqdGkiOiIxODQ2MTQ0MiIsIm5iZiI6MTcwNDI5MTg4OSwiZXhwIjoxNzA0MjkyMTg5fQ.WYgjdpw24SLMsVi3qCTtmLj5wxXE4jazbaKTOBk_pImDkTWUrEVxrnvCersxYLrssI_1HtezbIuIUO24wLQmTw/?Authorization=
Downloads
Additional Files
Published
How to Cite
Issue
Section
License
Copyright (c) 2024 Hérica Núbia Cardoso Cirilo, Amanda Ribeiro Feitosa, Gabriela Soares da Silva
This work is licensed under a Creative Commons Attribution 4.0 International License.
Cessão de Primeira Publicação à HU Revista
Os autores mantém todos os direitos autorais sobre a publicação, sem restrições, e concedem à HU Revista o direito de primeira publicação, com o trabalho licenciado sob a Licença Creative Commons Attribution que permite o compartilhamento irrestrito do trabalho, com reconhecimento da autoria e crédito pela citação de publicação inicial nesta revista, referenciando inclusive seu DOI.
