Delaying pegaspargase during induction in adults with acute lymphoblastic leukaemia is associated with lower risk of high-grade hepatotoxicity without adversely impacting outcomes

Pegaspargase is a key drug for the treatment of younger adults with acute lymphoblastic leukaemia (ALL). Pegaspargase-associated hepatotoxicity is most common during induction, and its incidence increases with age and body mass index (BMI). We hypothesized that the delayed administration of pegaspargase during induction is associated with lower risk of hepatotoxicity while retaining efficacy. We retrospectively reviewed 141 adult patients with newly diagnosed ALL who received pegaspargase during induction from November 2013 to February 2024. There were 78 (55.3%) patients who received early pegaspargase (EP) on day 4 and 63 (44.7%) patients who received delayed pegaspargase (DP) on day 15. High-grade hepatotoxicity (grade ≥ 3 transaminitis and/or hyperbilirubinaemia) occurred more frequently in the EP group (p = 0.06). Rates of complete remission and negative minimal residual disease post induction were not different between cohorts. Univariate logistic regression analysis showed that BMI and age significantly predicted an increased risk of high-grade hepatotoxicity while DP was associated with a lower risk (odds ratio = 0.44; p = 0.04). Overall survival and event-free survival were not significantly different between cohorts. Delaying pegaspargase administration from day 4 to day 15 during induction cycle in adults with ALL might reduce the risk of high-grade hepatotoxicity without adversely impacting clinical efficacy outcomes.