Comparative assessment of asparaginase activity, population pharmacokinetics, and safety of biosimilar native Escherichia coli and pegylated asparaginase in children with newly diagnosed acute lymphoblastic leukemia: a pharmacometrics-based randomized clinical trial.

backgroundThere is a paucity of data regarding the comparison of asparaginase activity, pharmacokinetics, pharmacodynamic outcomes, and safety of biosimilar native E.coli asparaginase (N-Asp) and biosimilar pegylated asparaginase (P-Asp) used in India.

methodsA randomized, open-labeled, population pharmacokinetic (PopPK) and pharmacodynamic trial comparing the N-Asp (10,000 IU/m

resultsFourteen patients were randomized to each arm. The asparaginase activity of 434[interquartile range(IQR) 259, 629] IU/L was observed in the P-Asp compared (p-0.04) to the N-Asp group 64[IQR 27, 184] IU/L on day 33 of the induction phase of chemotherapy. The anti-asparaginase antibody formation, minimal residual disease, and safety were comparable between both groups. The interindividual variability of the population parameters in the PopPK model was higher with N-Asp than P-Asp. The subtherapeutic trough levels of asparaginase were observed more in the N-Asp group (9/14 in N-Asp vs. 0/14 in P-Asp, p < 0.01).

conclusionThe asparaginase activity was higher with P-Asp at d33. P-Asp demonstrated less interindividual variability and a predictable kinetic profile, supporting its preferability over N-Asp for first-line management of ALL in the Indian pediatric population. While routine TDM for trough level monitoring may be less critical with P-Asp, TDM retains value to identify silent inactivation, differentiate hypersensitivity from infusion reactions, and confirm adequate activity in high-risk scenarios. In contrast, the higher variability of N-Asp strongly warrants the use of TDM. CLINICAL TRIAL REGISTRATION IDENTIFICATION: CTRI/2019/06/019520 registered on 04/June/2019.