Evaluating the Role of Anti-PEG Antibodies in Hypersensitivity to PEG-Asparaginase Through Clinically Relevant Cut-Points Defined by ELISA and Surface Plasmon Resonance

Background/Objectives: Conjugation of polyethylene glycol (PEG) to L-asparaginase (ASP) reduces immunogenicity and prolongs the half-life of this biological drug used to treat acute lymphoblastic leukemia (ALL). However, some patients develop anti-drug antibodies (anti-ASP and anti-PEG), which may impair efficacy through neutralization or faster elimination and may cause hypersensitivity reactions. Their clinical impact remains debated, partly due to variability in analytical methods and cut-points often defined by statistical rather than clinical outcomes.