(011) Asparaginase Therapeutic Drug Monitoring: Utility of Peak and 7-Day Serum Asparaginase Activity Levels as Surrogate Markers for Day 14 Serum Asparaginase Activity

Poster Abstract:

Background: Asparaginase is a crucial component of multiagent treatment of acute lymphoblastic leukemia (ALL) and lymphoblastic lymphoma (LLy), with early discontinuation shown to adversely affect outcomes. Historically, administration of pre-medications prior to asparaginase doses has been discouraged out of concern for masking hypersensitivity reactions, which can indicate reduced serum asparaginase activity (SAA). To ensure complete asparagine depletion, monitoring SAA levels is recommended when utilizing pre-medications. Surrogate time points for checking SAA levels have been proposed, but there is no universal recommendation of best time point to ensure a patient does not have rapid clearance or anti-drug antibody neutralization anti-drug (silent inactivation). Since August 2022, our institution has expanded therapeutic drug monitoring of long-acting asparaginase products (pegaspargase and calaspargase pegol) to include peak (1-24 hours post-infusion), 7-day post-infusion (± 2 days), and 14-day post-infusion (± 2 days) levels for each dose, beginning with the second dose. While this serves to ensure patient is therapeutic at day 14, earlier data allow for capturing rapid clearance and early intervention. Ultimately, the goal is to decrease the number of levels drawn with each long-acting asparaginase dose in favor of a standard time point.

Objectives: The primary objective of this study is to determine the utility of peak and 7-day post-infusion SAA levels as surrogate markers for day 14 SAA level. Secondary objectives are to determine which SAA level(s) most accurately capture patients who have rapid clearance or silent inactivation, identify patient population(s) at increased risk of rapid clearance or silent inactivation, assess for correlation of asparaginase characteristics (product, dose number, dose received) and SAA levels, describe proportion of patients requiring transition to short-acting asparaginase product and clinical rationale for transition, and describe asparaginase-related toxicities encountered in this patient population and correlate with asparaginase characteristics and SAA levels.

Methods: This single-center, retrospective cohort study was completed at a pediatric academic medical center. Patients aged 1-21 years with a diagnosis of ALL or LLy who received pegaspargase or calaspargase pegol at dose of 2500 IU/m2 (± 10%) between August 1, 2022 and November 30, 2023 were included. Patients were excluded if they did not have SAA levels drawn during the study period. Patient data, oncologic diagnosis, treatment protocol, asparaginase dose and related toxicities, use of pre-medications, and SAA levels were collected. Descriptive statistics will be performed on each variable in the data set.

Results: pending

Conclusion: pending

References (must also be included in final poster): 1. Gupta S, Wang C, Raetz EA, et al. Impact of Asparaginase Discontinuation on Outcome in Childhood Acute Lymphoblastic Leukemia: A Report From the Children's Oncology Group. J Clin Oncol. 2020;38(17):1897-1905. doi:10.1200/JCO.19.03024
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