Achievement of therapeutic levels using dose-reduced peg-asparaginase in adult patients with acute lymphoblastic leukemia.

6530 Background: Peg-asparaginase (PEG) doses range from 2000-2500 IU/m 2 in pediatric-inspired regimens for acute lymphoblastic leukemia (ALL). Pediatric PEG dosing in adolescents and young adults (AYAs) has resulted in improved outcomes, but PEG-associated toxicities increase with age and often limit its use. Therapeutic dosing is determined by asparagine (ASP) depletion for 14 days after dose; L-asparaginase levels can act as a surrogate marker of ASP depletion. We previously showed dose reduced PEG (defined as 1000 IU/m 2 . Induction median dose was 1000 IU/m 2 . Among those with PEG trough levels, 79% were therapeutic after induction; of note, 4 patients were transitioned from PEG to Erwinia asparaginase due to silent inactivation. During induction, 23 (48%) patients had ≥1 grade 3+toxicity, including 5 (10%) with hepatotoxicity, 1 (2%) with pancreatitis, and 2 (4%) with a thrombotic event. There was no statistical relationship between dose level and toxicities (p=.8). Conclusions: This study demonstrates durability of therapeutic L-asparaginase levels and ASP depletion that persists 14 days despite dose reduction. There were decreased rates of hepatotoxicity and comparable rates of pancreatitis and thrombotic events compared to rates reported in CALBG 10403 (C10403) (Stock et al, Blood 2019), which utilized standard pediatric dosing. In addition, our cohort’s median age was significantly older than those treated on C10403. This suggests PEG dose reduction may offer similar therapeutic ASP depletion with comparable or reduced toxicities. Dose reduction should be studied prospectively in AYAs with ALL. Table: see text