Desensitization to calaspargase pegol appears to be less successful than pegaspargase

Asparaginase is a critical component in the treatment of pediatric acute lymphoblastic leukemia (ALL), and children who are unable to complete their intended course of asparaginase therapy tend to have poorer outcomes. 1This underscores the importance of optimizing the delivery of planned asparaginase therapy.Pegaspargase, a pegylated asparaginase product, has been the preferred asparaginase formulation in the United States since the withdrawal of native L-asparaginase from the market in 2012. 2 As of 1 December 2022, pegaspargase became unavailable for patients aged one month to 21.5 years of age, leaving calaspargase pegol (CAL-PEG) as the only primary asparaginase option for pediatric patients in the United States.CAL-PEG was approved by the US Food and Drug Administration in 2018 for pediatric patients based on results from the Children's Oncology Group study AALL07P4 and Dana-Farber Cancer Institute (DFCI) trial 11-001. 3DFCI 11-001 protocol reported a postinduction CAL-PEG allergy rate (grade 2) of 15%, while the AALL07P4 study reported allergy rates up to 27.3% (grades 1-4). 4,5though literature supports the effectiveness of desensitization following pegaspargase allergy, data on the feasibility or success of CAL-PEG desensitization remain limited, with only 2 cases reported to date. [6][7]][8][9][10][11][12] Here, we describe our experience with CAL-PEG desensitization in both front-line and relapsed ALL therapy.Patients desensitized to CAL-PEG from 1 December 2022 to 30 September 2024 at St. Jude Children's Research Hospital were retrospectively reviewed.This research received approval from the St. Jude institutional review board.A 12-step, 3-bag method was used for CAL-PEG desensitization (Table 1). 6Premedications given to all patients before desensitization included diphenhydramine, hydrocortisone, famotidine, and montelukast.The prepared CAL-PEG desensitization bags were infused within 4 hours when stored at room temperature and within 24 hours when refrigerated after preparation. 13Nurses were instructed to keep bag 3 refrigerated until step 6.Desensitization was considered successful if the infusion was completed and serum asparaginase activity (SAA) was estimated to remain 0.1 IU/mL for at least 21 days.If the first desensitization was successful, subsequent desensitization doses were administered.Measurement of SAA levels was carried out by our Clinical Laboratory Improvement Amendments-certified pharmacokinetics laboratory using methods previously described. 14linear 1-compartment model with Michaelis-Menten elimination (parameterized in terms of Vmax, Km, and V) was applied to the data using non-linear mixed-effects modeling with the stochastic approximation expectation-maximization approach (Monolix, 2023R1).The inter-individual variability and interoccasion variability of the parameters were assumed to be log-normally distributed.Activity values below the lower limit of quantification (0.06 IU/mL) were treated as censored, and the M3 method was used for handling these values (as implemented in Monolix; Beal JPP, 2001).A proportional residual error model was used, assuming a normal distribution of the residuals.Individual post hoc estimates (the