Impact of obesity on asparaginase dosing and outcomes in adult patients with ALL

The use of asparaginase is challenging in older and/or obese adults with acute lymphoblastic leukemia (ALL) due to the higher risk of asparaginase-related toxicities; this has resulted in its selective use or avoidance in these patient populations.¹

Here, we summarize a review published by Cassaday et al.¹ in Best Practice & Research Clinical Haematology on the impact of obesity on outcomes with asparaginase-containing regimens in patients with ALL, as well as recommendations for the use of asparaginase.  

Key findings

Impact of obesity on outcomes

Key data from selected studies on the impact of obesity on outcomes and risks with asparaginase-containing regimens for children, adolescents, and adults with ALL are summarized in Figure 1; increasing age can also increase these risks.

Figure 1. Key findings on the impact of obesity with asparaginase-containing regimens* 

ALT, alanine aminotransferase; BSA, body surface area; BMI, body mass index; COG, Children’s Oncology Group; DFCI, Dana Farber Cancer Institute; DFS, disease-free survival; EFS, event-free survival; OS, overall survival.
*Adapted from Cassaday.¹

 Strategies to optimize the use of asparaginase

• Use of shorter-acting asparaginase products
• Cap the dose of pegaspargase
• Switch to a non-asparaginase-containing regimen, such as hyperCVAD

Clinical approach to asparaginase-containing regimens in adult ALL

A clinical approach to asparaginase-containing regimens in adult ALL is presented in Figure 2.

• Pegaspargase is routinely capped at a dose of 3,750 units to reduce the risk of toxicities
• A lower dose of pegaspargase (e.g., 1,000 units/m²) or switching to another regimen, such as hyperCVAD, should be considered
• Weight loss should be encouraged to reduce the risk of complications

Figure 2. Clinical approach to asparaginase-containing regimens in adult ALL*

ALL, acute lymphoblastic leukemia; BMI, body mass index; NSAA, nadir serum asparaginase activity assessment.
*Adapted from Cassaday.¹