Activity and Toxicity of Intravenous Erwinia Asparaginase Following Allergy to E. coli‐Derived Asparaginase in Children and Adolescents With Acute Lymphoblastic Leukemia

BACKGROUND: Erwinia asparaginase is antigenically distinct from E.coli‐derived asparaginase and may be used after E.coli‐derived asparaginase hypersensitivity. In a single‐arm, multicenter study, we evaluated nadir serum asparaginase activity (NSAA) and toxicity with intravenously administered asparaginase Erwinia chrysanthemi (IV‐Erwinia) in children and adolescents with acute lymphoblastic leukemia (ALL) or lymphoblastic lymphoma with hypersensitivity to E.coli‐derived asparaginase. PATIENTS AND METHODS: Between 2012 and 2013, 30 patients (age 1–17 years) enrolled from 10 centers. Patients received IV‐Erwinia, 25,000 IU/m(2)/dose on Monday/Wednesday/Friday, for 2 consecutive‐weeks (6 doses = 1 cycle) for each dose of pegaspargase remaining in the original treatment plan. The primary objective was to determine the proportion of patients achieving NSAA ≥0.1 IU/ml 48 hr after dose 5 in Cycle 1. Secondary objectives included determining the proportion achieving NSAA ≥0.1 IU/ml 72 hr after Cycle 1 dose 6, and the frequency of asparaginase‐related toxicities. RESULTS: Twenty‐six patients completed Cycle 1; 24 were evaluable for NSAA assessment. In Cycle 1, NSAA ≥0.10 IU/ml was detected in 83% of patients (95% confidence interval [CI], 63–95%) 48 hr post‐dose 5 (mean ± SD; 0.32 IU/ml ± 0.23), and in 43% (95% CI, 22–66%) 72 hr post‐dose 6 (mean ± SD; 0.089 IU/ml ± 0.072). For all 30 patients over all cycles, hypersensitivity/infusional reactions with IV‐Erwinia occurred in 37%, pancreatitis 7%, and thrombosis 3%. CONCLUSIONS: IV‐Erwinia administration in children/adolescents appeared feasible and tolerable. A therapeutically‐effective NSAA (≥0.10 IU/ml) was achieved in most patients at 48 hr, but in fewer than half 72 hr post‐dosing, suggesting that monitoring NSAA levels and/or every 48 hr dosing may be indicated. Pediatr Blood Cancer 2015. © 2015 Wiley Periodicals, Inc.