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Impact of delaying pegaspargase during induction on hepatotoxicity in adult patients with ALL
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Pegaspargase-associated high-grade hepatoxicity occurs in 24–50% of adult patients with ALL, with incidences increasing with older age, obesity, and higher doses.1 Delaying pegaspargase dosing during induction was hypothesized to improve the hepatoxicity profile. A retrospective analysis assessed the impact of early pegaspargase (Day 4 ± 2; EP) vs delayed pegaspargase (Day 15 ± 2; DP) dosing during induction in 141 adult patients with ND ALL.1 Results from this analysis were published in the British Journal of Haematology by Tinajero, et al.1 |
| Key learnings |
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Patients who received EP had a numerically higher incidence of Grade ≥3 hepatotoxicity compared with patients who received DP, although this did not reach statistical significance (34.6% vs 19%; p = 0.06). |
| Clinical efficacy outcomes were similar between patients who received EP vs DP, including CR/CRi rates (89.7% vs 79.4%; p = 0.13), MRD-negativity rates (61.4% vs 58%; p = 1), OS (p = 0.59), and EFS (HR, 0.70; 95% CI, 0.39–1.26). |
| More patients who received EP required post-pegaspargase chemotherapy dose modifications during induction compared with patients who received DP (23.1% vs 4.8%; p <0.01). |
| Results suggest that delaying pegaspargase during induction may reduce hepatoxicity and maintain chemotherapy dose intensity without negatively impacting efficacy outcomes in adult patients with ALL. |
Abbreviations: ALL, acute lymphoblastic leukemia; CI, confidence interval; CR, complete remission; CRi, complete remission with incomplete count recovery; DP, delayed pegaspargase; EFS, event-free survival; EP, early pegaspargase; ND, newly diagnosed; MRD, measurable residual disease; OS, overall survival.
- Tinajero J, Xu S, Ngo D, et al. Delaying pegaspargase during induction in adults with acute lymphoblastic leukaemia is associated with lower risk of high-grade hepatotoxicity without adversely impacting outcomes. Br J Haematol. 2024. Online ahead of print. DOI: 10.1111/bjh.19880
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