Asparaginase-associated toxicities in pediatric and AYA patients with ND ALL

Results from a study by the Children’s Oncology Group, evaluating asparaginase-associated toxicities (AATs) in pediatric and adolescent and young adult (AYA) patients with newly diagnosed (ND) acute lymphoblastic leukemia (ALL; N = 4,925), were published in Blood Advances by Orgel et al. The primary objective was to determine the effect of body mass index (BMI), body surface area (BSA), and/or age on the risk of developing ≥1 AAT during early therapy. Secondary objectives included the risk factors for each AAT and the association of AAT during induction with the presence of measurable residual disease (MRD) at the end of induction (EOI).

Key data: Overall, 6% of patients experienced ≥1 AAT during induction. The prevalence of AATs increased with escalating obesity class (Class 1, 8.6%; Class 2, 16.9%; Class 3, 17.2%; p = 0.001). Multivariable analyses revealed that obesity and high BSA together (odds ratio [OR], 3.3; 95% confidence interval [CI], 2.22–4.77) were associated with increased risk of developing an AAT, while high BSA without obesity was not associated with an increased risk of AATs (OR, 1.4; 95% CI, 0.94–2.04). Increasing age was also associated with a higher risk of developing AATs. At the EOI, the prevalence of MRD positivity did not differ between patients who experienced ≥1 AAT vs those who experienced no AATs.

Key learning: Obesity, but not high BSA alone, conferred a greater risk of developing AATs in pediatric and AYA patients with ND ALL. Older age at diagnosis was also identified as an independent predictor of AAT development, suggesting that these higher-risk patients may benefit from closer monitoring.