Intramuscular recombinant Erwinia asparaginase, JZP458, effectively maintains adequate nadir serum asparaginase activity in patients with acute lymphoblastic leukemia or lymphoblastic lymphoma (ALL/LBL) and has a safety profile similar to other asparaginases, according to research published in Blood.
The findings are from the phase 2/3 study AALL1931 (ClinicalTrials.gov Identifier: NCT04145531), which was conducted in collaboration with the Children’s Oncology Group. The researchers evaluated the efficacy and safety of JZP458 in patients with ALL/LBL who developed hypersensitivity or silent inactivation to Escherichia coli-derived asparaginases.
Each dose of E coli-derived asparaginase remaining in patients’ treatment plans was substituted by 6 doses of intramuscular JZP458 on Mondays, Wednesdays, and Fridays (MWF). The investigators evaluated 3 regimens: 25 mg/m2 MWF, 37.5 mg/m2 MWF, and 25/25/50 mg/m2 MWF. They assessed efficacy by the proportion of patients maintaining adequate nadir serum asparaginase activity (NSAA ≥0.1 IU/mL) at 72 hours (primary endpoint) and 48 hours (key secondary endpoint) during the first treatment course.
A total of 167 patients, with median age of 10 years (range, 1-25; 87% aged <18 years), were included in the study (25-mg/m2 cohort, n=33; 37.5-mg/m2 cohort, n=83; and 25/25/50-mg/m2 cohort, n=51). Mean serum asparaginase activity levels at 72 hours were 0.16 IU/mL in the 25-mg/m2 cohort, 0.33 IU/mL in the 37.5-mg/m2 cohort, and 0.47 IU/mL in the 25/25/50-mg/m2 and at 48 hours were 0.45 IU/mL in the 25-mg/m2 cohort, 0.88 IU/mL in the 37.5-mg/m2 cohort, and 0.66 IU/mL in the 25/25/50-mg/m2 cohort.
The investigators reported that following the first treatment course of JZP458, the proportion of patients who achieved NSAA levels ≥0.1 IU/mL at 72 hours was 64% in the 25-mg/m2 cohort, 91% in the 37.5-mg/m2 cohort, and 90% in the 25/25/50-mg/m2 cohort and at 48 hours, 97% in the 25-mg/m2 cohort, 99% in the 37.5-mg/m2 cohort, and 96% in the 25/25/50-mg/m2 cohort..
The investigators reported that grade 3/4 treatment-related adverse events (AEs) occurred in 51% of patients. The most common reason for discontinuation was AEs (13%; pancreatitis [6%], allergic reactions [5%], increased alanine aminotransferase [1%], and hyperammonemia [1%]).
“[Intramuscular] JZP458 using the dosing regimen of 25/25/50 mg/m2 MWF is efficacious, is tolerable, and achieves NSAA levels ≥0.1 IU/mL at both 48 and 72 hours in the vast majority of patients. The safety profile of JZP458 is consistent with what has been described for other asparaginase products,” the researchers concluded in their report.
Limitations of the study included the single-arm design and that all patients had not some patients had not completed treatment at data cutoff.
Disclosure: This research was supported by Jazz Pharmaceuticals. Please see the original reference for a full list of disclosures.
Maese L, Loh ML, Choi MR, et al. Recombinant Erwinia asparaginase (JZP458) in acute lymphoblastic leukemia: results from the phase 2/3 AALL1931 study. Blood. 2023;141(7):704-712. doi:10.1182/blood.2022016923