How can therapeutic drug monitoring and premedication be applied in clinical practice to optimize pegaspargase treatment in patients with ALL?

The ALL Hub was pleased to speak with Carmelo Rizzari, University of Milano-Bicocca, Monza, IT. We asked, How can therapeutic drug monitoring and premedication be applied in clinical practice to optimize pegaspargase treatment in patients with acute lymphoblastic leukemia (ALL)?

Key points

• Pegaspargase is a key component of modern multi-agent chemotherapy regimens for the treatment of acute lymphoblastic leukemia (ALL) and is widely used due to its proven efficacy and favorable pharmacologic profile.¹
• However, clinical hypersensitivity to pegaspargase may indicate the development of anti-asparaginase antibodies, which can reduce or neutralize enzymatic activity and lead to ineffective treatment.^1,2
• Therapeutic drug monitoring of serum asparaginase activity enables clinicians to confirm adequate drug exposure, maintain uninterrupted treatment, and optimize outcomes.^1,2
• Asparaginase activity levels provide a surrogate marker of asparagine depletion (the main aim of pegaspargase therapy).²
  • A trough serum asparaginase activity level of ≥ 0.1 IU/mL is considered a safe and appropriate target level at 7 days post administration.^1,2
• Monitoring is also valuable in identifying silent inactivation (loss of activity without overt allergy) and in distinguishing true allergic reactions from non-allergic clinical events.^1,2
• Switching to other treatments may in some cases be avoided using premedication with steroids and/or antihistamines to reduce allergic-like reactions.^1,2
  • Premedication can reduce allergic-like reactions and improve tolerability, facilitating full-dose administration; however, it must be combined with therapeutic drug monitoring to detect silent inactivation, which premedication does not prevent.
• In conclusion, pegaspargase drug monitoring and premedication can enhance clinical effectiveness, guide treatment decisions, and improve patient outcomes.¹

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