What dose of PEG-asparaginase do you recommend for teens with high BMI treated on a pediatric ALL regimen?
The peg-asparaginase dosing we use in ALL regimens for B and T cell is below:
Patients less than 21 years old – 2500 units/m2
Patients 21 years and older – 2000 units/m2
For obese patients (defined as > 95% BMI for patients less than 20 years old or BMI > 30 for patients 20 years and older), peg-asparaginase dose will be maxed at 3750 units.
For older adolescents and young adult patients, the optimal dosing of peg-asparaginase is unclear. It is recognized that asparaginase toxicity increases with age, but also with certain comorbid conditions such as diabetes, liver disease, and obesity (BMI >30).
The adolescent and young adult (AYA) ALL protocols in the adult cooperative groups use a peg-asparaginase dose of 2000 international units/m2 and cap the dose at 3750 international units for all patients.
Further modifications to peg-asparaginase dosing can be considered, however, for younger patients with comorbid conditions (BMI>30) who are at risk for significant toxicity (especially during induction therapy) with the monitoring of asparaginase activity levels. Asparaginase activity levels can be obtained by a commercially available assay for therapeutic drug monitoring.
Derman et al have demonstrated that adequate asparaginase enzyme levels and less toxicity can be achieved with reduced peg-asparaginase (1000 IU/m2) dosing in older patients (Derman et al., PMID 31680584). Further data using this approach for older adults was presented at ASH 2020 (Anand Ashwin Patel, Abstract 2796). I have used this approach of reduced dosing and monitoring the asparaginase activity levels for some younger patients with comorbid conditions to prevent severe toxicities while also achieving the improved clinical outcomes of the pediatric inspired regimens for AYA patients.