Continuous PEGasparaginase Dosing Reduces Hypersensitivity Reactions in Pediatric ALL:A Dutch Childhood Oncology Group ALL11 Randomized Trial

PURPOSE: The primary objective of this randomized study was to determine whether a continuous dosing schedule (without the asparaginase-free interval) would result in less hypersensitivity reactions to PEGasparaginase (PEGasp) compared with the standard noncontinuous dosing schedule. METHODS: Eight hundred eighteen patients (age 1-18 years) with ALL were enrolled in the Dutch Childhood Oncology Group-ALL11 protocol and received PEGasp. Three hundred twelve patients stratified in the medium-risk arm were randomly assigned to receive 14 individualized PEGasp doses once every two weeks in either... Mehr ...

Verfasser: Van Der Sluis, Inge M.
Brigitha, Leiah J.
Fiocco, Marta
De Groot-Kruseman, Hester A.
Bierings, Marc
Van Den Bos, Cor
De Haas, Valerie
Hoogerbrugge, Peter M.
Tissing, Wim J.E.
Veening, Margreet A.
Pieters, Rob
Dokumenttyp: Artikel
Erscheinungsdatum: 2024
Reihe/Periodikum: Van Der Sluis , I M , Brigitha , L J , Fiocco , M , De Groot-Kruseman , H A , Bierings , M , Van Den Bos , C , De Haas , V , Hoogerbrugge , P M , Tissing , W J E , Veening , M A & Pieters , R 2024 , ' Continuous PEGasparaginase Dosing Reduces Hypersensitivity Reactions in Pediatric ALL : A Dutch Childhood Oncology Group ALL11 Randomized Trial ' , Journal of Clinical Oncology , vol. 42 , no. 14 , pp. 1676-1686 . https://doi.org/10.1200/JCO.23.01797
Schlagwörter: /dk/atira/pure/sustainabledevelopmentgoals/good_health_and_well_being / name=SDG 3 - Good Health and Well-being
Sprache: Englisch
Permalink: https://search.fid-benelux.de/Record/base-29043529
Datenquelle: BASE; Originalkatalog
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Link(s) : https://pure.eur.nl/en/publications/11b67fbe-6ff6-45d3-8e07-3ca0ba07430c

PURPOSE: The primary objective of this randomized study was to determine whether a continuous dosing schedule (without the asparaginase-free interval) would result in less hypersensitivity reactions to PEGasparaginase (PEGasp) compared with the standard noncontinuous dosing schedule. METHODS: Eight hundred eighteen patients (age 1-18 years) with ALL were enrolled in the Dutch Childhood Oncology Group-ALL11 protocol and received PEGasp. Three hundred twelve patients stratified in the medium-risk arm were randomly assigned to receive 14 individualized PEGasp doses once every two weeks in either a noncontinuous or continuous schedule after the first three doses in induction (EudraCT: 2012-000067-25). Hypersensitivity reactions were defined as allergies, allergic-like reactions, and silent inactivation. Secondary end points were other asparaginase-related toxicities, asparaginase activity and antibody levels, and outcome. RESULTS: During induction, 27 of 818 patients (3.3%) experienced hypersensitivity reactions. After random assignment, 4 of 155 (2.6%) in the continuous treatment arm versus 17 of 157 (10.8%) patients in the noncontinuous treatment arm had hypersensitivity reactions (P <.01), of which two (1.3%) versus 13 (8.3%) were inactivating reactions (P <.01). The occurrence of inactivating hypersensitivity reactions was seven times lower in the continuous arm (odds ratio, 0.15 [0.032-0.653]). In addition, antibody levels were significantly lower in the continuous arm (P <.01). With exception of a lower incidence of increased amylase in the continuous arm, there were no significant differences in total number of asparaginase-associated toxicities between arms. However, the timing of the toxicities was associated with the timing of the asparaginase administrations. No difference in 5-year cumulative incidence of relapse, death, or disease-free survival was found between both treatment arms. CONCLUSION: A continuous dosing schedule of PEGasp is an effective approach to prevent antibody formation and ...