(140) Impact of Premedication on Hypersensitivity and Infusion-Related Reactions Prior to Administration of Pegylated Asparaginase Treatment in Children for Acute Lymphoblastic Leukemia and Lymphoma

Poster Abstract:

Background: The use of asparaginase products is critical in the treatment of pediatric acute lymphoblastic leukemia (ALL) and lymphoblastic lymphoma. Of all asparaginase products, pegylated (PEG)-asparaginase is the first-line agent in therapy protocols.1 The limiting factor to PEG-asparaginase is the risk of hypersensitivity and infusion-related reactions, resulting in disruption of infusion and potential drug substitution to more costly and frequent treatment. A retrospective chart review published in 2019 found premedication prior to PEG-asparaginase decreased rate of acute adverse events from 17.2% to 5.9% (P=0.017).2 In contrast, recent analysis of hypersensitivity rates at various institutions utilizing universal premedication has found no benefit in reducing moderate to severe hypersensitivity reactions.3

Objective: To evaluate differences in incidence of reactions between patients who were premedicated and those who were not premedicated prior to administration of asparaginase products.

Methods: This is a single-center, retrospective chart review of pediatric patients who received asparaginase products at Roswell Park Comprehensive Cancer Center (RPCCC) between January 1st, 2017 and December 31st, 2022. The electronic health records (EHR) were reviewed to determine if patients were premedicated and subsequent impact on the incidence and severity of hypersensitivity and infusion-related reactions. The primary endpoint is the incidence of documented hypersensitivity reactions.

Results: The primary analysis included 62 patients with a total of 898 administered doses. Despite pre-medication being given to 47% of the pediatric ALL and lymphoblastic lymphoma patients, 31% of patients had a hypersensitivity reaction. Of the remaining patients who did not receive pre-medications, 27% had a hypersensitivity reaction. The incidence of documented hypersensitivity reactions for all administered doses was 2.1% (19/898), of which 94.7% (18/19) were after administration of PEG-asparaginase. Seven patients were switched to asparaginase Erwinia chyrsanthemi or asparaginase Erwinia chyrsanthemi (recombinant)-rywn following a documented hypersensitivity reaction after the first dose of PEG- asparaginase. For patients that received additional doses of PEG-asparaginase, two reacted after the third dose and one patient reacted after the second dose despite administration of premedication.

Conclusion: Pre-medication prior to PEG-asparaginase did not affect the incidence or severity of hypersensitivity reactions and the difference, when compared to patients who were not pre-medicated, was not found to be statistically significant (P=0.7851). Large-multi center studies are needed to determine the role of premedication and find effective solutions to prevent discontinuation of PEG-asparaginase in the treatment of pediatric ALL and lymphoblastic lymphoma.

References (must also be included in final poster): 1. Fajardo AF, Cox S, MacDonald P, Millson S, Athale UH. Universal Premedication for Pegylated (PEG)-Asparaginase Treatment in Children with Acute Lymphoblastic Leukemia (ALL) and Lymphoblastic Lymphoma (LLy) Has No Impact on Frequency of Hypersensitivity Reactions. Blood. 2022;140(Supplement 1):6044-6045. doi:https://doi.org/10.1182/blood-2022-158844
2. Cooper SL, Young DJ, Bowen CJ, et al. Universal premedication and therapeutic drug monitoring for asparaginase‐based therapy prevents infusion‐associated acute adverse events and drug substitutions. Pediatric Blood & Cancer. 2019;66(8). doi:https://doi.org/10.1002/pbc.27797
3. Hughes CR, Bernardo V, Youssef S, et al. Premedication and Longer Infusion Time Do Not Reduce the Incidence of Hypersensitivity Reactions to Pegaspargase. Blood. 2020;136(Supplement 1):4-5. doi:https://doi.org/10.1182/blood-2020-143248
4. Bernard C, Rustay NR, Mamedov KA. Use of Premedication Prior to Asparaginase (ASNase) Administration in Pediatric Acute Lymphoblastic Leukemia (ALL): Effect on Treatment Completion Rate. Blood. 2017;130:5574-5574. doi:https://doi.org/10.1182/blood.v130.suppl_1.5574.5574
5. Aldoss I, Yin J, Wall A, et al. The impact of early PEG-asparaginase discontinuation in young adults with ALL: a post hoc analysis of the CALGB 10403 study. Blood Advances. 2023;7(2):196-204. doi:https://doi.org/10.1182/bloodadvances.2022007791