Lack of benefit from premedication for pegylated asparaginase during pediatric acute lymphoblastic leukemia/lymphoma therapy: A side-by-side comparison

Background: Pegylated l-asparaginase (PEG) is integral to treatment regimens for acute lymphoblastic leukemia (ALL) and lymphoma. Hypersensitivity reactions (HSRs) to PEG are common and can preclude continued administration. Data supporting recommendations for universal premedication (UPM) prior to PEG infusion to reduce incidence of HSRs are limited; UPM has become common practice.Procedures: Two free-standing children's hospitals independently implemented UPM prior to PEG infusions in 2016 and 2019, respectively. In a side-by-side retrospective analysis, incidence and severity of HSRs were analyzed pre- and postimplementation of UPM in youth >= 1 years old treated with frontline PEG-containing ALL regimens (2015-2018, 2016-2020). All HSRs were centrally reviewed within each institution to confirm and grade the HSR (Common Terminology Criteria for Adverse Events, v5). Planned analyses of subsets at potentially greater risk for HSRs included intensive PEG regimens (>= 5 doses), adolescent and young adults (AYA), Hispanic/Latinx ethnicity, and obesity.Results: In 410 patients (by institution, n = 282 and n = 128), the overall incidence of Grade >= 3 HSRs was 20% (56 out of 282) and 18% (23 out of 128), respectively. No difference in incidence of Grade >= 3 HSRs in patients with versus without UPM was found at either institution (23 vs. 19%, p = .487 and 19 vs. 17%, p = .845). UPM also did not reduce the severity of HSRs, nor influence HSR risk within any patient subset.Conclusions: UPM prior to PEG infusion did not alter incidence or severity of HSRs at either institution. HSR remains a common complication of PEG therapy, impacting the patient experience. Alternative strategies to reduce HSRs are urgently required.