Abstract C075: Study of L-Asparaginase Per-Day Decline and Its Association with Measurable Residual Disease (MRD) in Pediatric Acute Lymphoblastic Leukemia (ALL)

Abstract Background: L-Asparaginase (L-Asp) is an important drug in pediatric Acute Lymphoblastic Leukemia (ALL) treatment but is limited by anti-L-Asp antibody-mediated inactivation, with or without immediate hypersensitivity. PEGylated L-Asp offers reduced immunogenicity and prolonged activity, with a potential half-life of around 6-7 days. Drug activity is commonly assessed on Day 7 to evaluate mid-interval levels and on Day 14, which marks the end of the dosing interval- with trough levels ≥100 IU/L considered optimal for sustained therapeutic efficacy. Previous unpublished data from our institution showed no significant association between Day 7 or Day 14 suboptimal L-Asp levels and Measurable Residual Disease (MRD) positivity, prompting follow-up study if drug clearance status better predict MRD. Objective: To assess whether per-day drop in L-Asp activity between Days 7 and 14 correlates with MRD status Methodology: A post hoc analysis was conducted in 41 pediatric ALL patients using previously collected L-Asp trough level data measured on Days 7 and 14, employing the AHA-Indooxine colorimetric assay technique (710 nm). The per-day drop in L-Asp activity (Δ) was calculated as: [Day 14 activity - Day 7 activity] / 7. Patients were categorized based on the median Δ value (-18.3 IU/L/day) observed in MRD-positive cases: those with Δ ≤ -18.3 IU/L/day were classified as 'Fast drop' and those with Δ > -18.3 IU/L/day as 'Slow drop'. Outcomes between groups were compared using Fisher’s exact test. Results: MRD status (Positive/Negative): Due to 6 induction deaths, MRD was available in 35/41 patients. Among 13 patients in the Fast drop group, 8 (61.5%) were MRD-positive and 5 (38.5%) MRD-negative; among 22 patients in the Slow drop group, 7 (31.8%) were MRD-positive and 15 (68.2%) MRD-negative (P = 0.157). Day 14 trough (Optimal/Suboptimal): Among 15 Fast drop patients, 3 (20%) had suboptimal and 12 (80%) optimal levels; among 26 Slow drop patients, 10 (38.5%) were suboptimal and 16 (61.5%) optimal (P = 0.305). Age (<10/≥10 years): Of 15 Fast drop patients, 12 (80%) were <10 years and 3 (20%) ≥10 years; among 26 Slow drop patients, 16 (61.5%) were <10 years and 10 (38.5%) ≥10 years (P = 0.305). Conclusion: Although a higher proportion of suboptimal Day 14 L-Asp levels was hypothesized in the Fast drop group, the opposite trend was observed. This may partially explain the lack of correlation between suboptimal L-asparaginase levels and MRD positivity in our previous study. While P value not statistically significant, our results show higher MRD positivity in the Fast drop group, suggesting that the rate of drug drop (Δ) may be a more informative predictor than Day 14 trough alone. The predominance of younger children (<10 years) in the Fast drop group further suggests potential age-related differences in drug kinetics. These findings warrant validation in larger prospective studies incorporating detailed enzyme kinetics to optimize therapy. Citation Format: Bijurica Chakraborty, Praveen Kumar. Jha, Sounik Sarkar, Stuti Roy, Rajib De. Study of L-Asparaginase Per-Day Decline and Its Association with Measurable Residual Disease (MRD) in Pediatric Acute Lymphoblastic Leukemia (ALL) [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics; 2025 Oct 22-26; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2025;24(10 Suppl):Abstract nr C075.