Intravenous pegylated Escherichia coli asparaginase (PEG-asparaginase) was not more toxic than, was similarly efficacious to, and was associated with reduced anxiety compared with intramuscular native E. coli L-asparaginase in children with newly diagnosed acute lymphoblastic leukemia (ALL), a new study published online ahead of print in the journal The Lancet Oncology has shown.1
Because PEG-asparaginase has a longer half-life, is potentially less immunogenic, and can be more feasibly administered intravenously than L-asparaginase, researchers at Dana-Farber Cancer Institute in Boston, MA, sought to compare the efficacy and toxicity of intravenous PEG-asparaginase and intramuscular native L-asparaginase in pediatric patients with newly diagnosed ALL.
For the multicenter, open-label, phase 3 trial, researchers enrolled 551 patients 1 to 18 years with newly diagnosed ALL and were assigned to an initial risk group based on their baseline characteristics.
Participants then underwent 32 days of induction therapy, of which 526 achieved complete remission after induction.
Of those, 463 were then randomly assigned to receive 15 doses of intramuscular native E. coli L-asparaginase 2500 IU/m2 every 2 weeks or 30 weekly doses of intravenous PEG-asparaginase 25 000 IU/m2, beginning at week 7 after study entry.
Results showed that after a median follow-up of 6.0 years, the 5-year disease-free survival was 90% (95% CI, 85 – 93) for PEG-asparaginase and 89% (95% CI, 85 – 93) for L-asparaginase (P = .58).
In regard to toxicity, there was no significant difference in the overall frequency of asparaginase-related adverse events or in the individual frequency of allergy, pancreatitis, or thrombotic or bleeding complications. The most common grade 3 or higher adverse events were bacterial or fungal infections and asparaginase-related allergic reactions.
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The study also demonstrated significantly more anxiety associated with intramuscular L-asparaginase than intravenous PEG-asparaginase.
The findings support “[PEG-asparaginase’s use as the front-line asparaginase preparation in children with newly diagnosed acute lymphoblastic leukemia,” the authors concluded.
- Place AE, Stevensons KE, Vrooman LM, et al. Intravenous pegylated asparaginase versus intramuscular native Escherichia coli L-asparaginase in newly diagnosed childhood acute lymphoblastic leukaemia (DFCI 05-001): a randomised, open-label phase 3 trial [published online ahead of print November 5, 2015]. Lancet Oncol. doi: 10.1016/S1470-2045(15)00363-0.