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Background: In late 2022, pegaspargase (SS-PEG) became unavailable to patients younger than 22 years in the United States, leaving calaspargase pegol (SC-PEG) as the only available long-acting asparaginase formulation. SC-PEG has been compared to SS-PEG in two randomized, pediatric clinical trials and found to have similar rates of adverse events with comparable rates of event-free survival. Our institution uses a desensitization protocol for patients who experience a hypersensitivity reaction to asparaginase. Here we review our experience with desensitization since the transition to SC-PEG from SS-PEG. Objectives: To compare the rate of hypersensitivity reactions, success of desensitization protocols, and need for alternative asparaginase preparations between patients receiving SC-PEG and SS-PEG at our institution. Design/Method: This is a retrospective, single center study of pediatric patients who received at least 2 doses of SC-PEG between November 2022 and December 2023. Results: We report on 26 patients with acute lymphoblastic leukemia and lymphoblastic lymphoma who received at least two doses of SC-PEG. The frequency of a grade 2 or higher clinical hypersensitivity reaction in those who received SC-PEG was 42.3% (n=11). Silent inactivation, defined as serum asparaginase activity (SAA) <0.1 IU/mL measured seven days following dosing, occurred in an additional 7.8% (n=2). Ten patients underwent SC-PEG desensitization using a protocol that was identical to our previously published protocol using SS-PEG (August, et al., Ped Blood Cancer, 2020). In the desensitization protocol, patients were premedicated with prednisone, cetirizine, famotidine, and montelukast. SC-PEG 2500 IU/m2 was divided into three fractions of 1:100, 1:10, and 1:1 dilution. Each fraction was infused over approximately 60 minutes, increasing the rate every 15 minutes. Desensitization was tolerated with appropriate SAA levels (0.1 IU/mL) in 30% (n=3) of patients, 60% tolerated the infusion but had inappropriately low AA levels (n=6), and one patient did not complete the infusion due to an adverse event. Six patients received Rylaze following SC-PEG hypersensitivity, silent inactivation, or unsuccessful desensitization. Compared to our prior experience with SS-PEG desensitization where 17 out of 21 attempts were successful with appropriate SAA levels (August, et al., ASH, 2022), our success rate using SC-PEG (7 failures out of 10 attempts) is significantly less (p=0.013), leading to an increase in the use of an alternative asparaginase preparation. Conclusion: Our single institution experience with SC-PEG shows a high rate of hypersensitivity reactions, a high likelihood of failure of asparaginase desensitization compared to our historical experience, and the frequent need to switch to an alternative asparaginase preparation.




Presented at the 2024 American Society of Pediatric Hematology/Oncology (ASPHO) Conference; April 2-5, 2024; Seattle, WA.

An Increased Failure Rate of Asparaginase Desensitization with Calaspargase Pegol

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