Higher Rates of Hypersensitivity Reactions to Calaspargase Compared With Pegaspargase: A Single Center Retrospective Review

Abstract

Background: Asparaginase is a critical component of curative therapy for the treatment of pediatric acute lymphoblastic leukemia (ALL) and acute lymphoblastic lymphoma (LLy). Pegaspargase (PEG) increased the duration of asparagine depletion and lowered the incidence of hypersensitivity reactions (HSRs) compared with native asparaginase. When a second pegylated product, Calasparagase pegol-mknl (Cal-PEG) replaced PEG, we observed an increased incidence of HSR, defined as anaphylaxis or silent hypersensitivity. This led to a single center, retrospective review to determine the incidence of HSR in patients with ALL or LLy who received Cal-PEG or PEG. Procedure: Electronic medical records of all patients who received at least two doses of Cal-PEG (December 2022–December 2023) or PEG (December 2019–December 2022) were reviewed. Result: Overall, patients who received Cal-PEG had a significantly increased rate of asparaginase-related HSR compared with patients who received PEG. Twenty-one of 44 (48%) patients receiving Cal-PEG and 35 out of 154 (23%) of patients receiving PEG experienced Grade 3 or higher anaphylaxis, or silent hypersensitivity (p = 0.001). After 2:1 matching based on propensity scoring for confounding variables, patients who received Cal-PEG continued to have a statistically significantly higher rates of HSR, with HSR occurring in 21 out of 44 (48%) and 26 out of 88 (30%) patients receiving Cal-PEG and PEG, respectively (p = 0.04). Conclusion: The current administration of Cal-PEG in large cooperative group trials will allow for a postmarketing exploration of the true risk of HSR and associated patient-specific risk factors.