TOPLINE

Obesity and older age were associated with an increased risk for severe asparaginase-associated toxicities (AAT) during induction therapy in young patients with acute lymphoblastic leukemia (ALL), although AAT did not affect end-of-induction minimal residual disease (MRD) outcomes.

METHODOLOGY

• Researchers analyzed induction data from two Children’s Oncology Group frontline ALL trials to determine whether age, BMI, or body surface area affected risk of AAT and whether those toxicities influenced end-of-induction MRD.
• They included 4925 patients aged 1-30 years with newly diagnosed ALL. All patients received a single dose of pegylated asparaginase on days 4-6 without dose capping.
• AAT of interest included grade ≥ 3 hyperbilirubinemia, grade ≥ 4 alanine aminotransferase (ALT) elevation, grade ≥ 2 thromboembolic events, and grade ≥ 3 acute pancreatitis.

TAKEAWAY

• Overall, 6% of patients developed at least one treatment-impacting AAT during induction, and rates increased with age.
• Patients with obesity and high body surface area had a significantly higher risk for AAT than those without obesity and low body surface area (BSA) (adjusted odds ratio [aOR], 3.3; P < .0001).
• Older age was independently associated with AAT risk, with patients aged ≥ 21 years showing higher risk than those aged < 10 years (aOR, 3.3; P = .002).
• AAT during induction was not associated with poorer MRD outcomes at end of induction.

IN PRACTICE

"Identifying populations at highest risk for severe AAT is critical for optimizing safe delivery of asparaginase in the context of multiagent chemotherapy," the authors of the study wrote.

SOURCE

The study was led by Etan Orgel, MD, Children's Hospital Los Angeles. It was published online on July 15 in Blood Advances.

LIMITATIONS

The trials mostly enrolled younger children and adolescents. Data on infection, critical illness, and preexisting fatty liver disease were not routinely collected. The study only examined the induction phase and did not assess toxicities beyond induction.

DISCLOSURES

The study was supported by grants from the National Institutes of Health and the St. Baldrick's Foundation. Several authors reported consulting fees, honoraria, or research support from Jazz Pharmaceuticals; Servier Pharmaceuticals; Syndax Pharmaceuticals; and other organizations. Additional author disclosures are reported in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.