Recombinant Erwinia asparaginase (JZP458) in acute lymphoblastic leukemia/lymphoblastic lymphoma (ALL/LBL): Post hoc analysis of adverse events of interest from AALL1931.
Year: 2024
Type: conference-abstract
Abstract: 6521 Background: The pivotal Children’s Oncology Group Study AALL1931 (NCT04145531) evaluated JZP458, a recombinant Erwinia asparaginase (ASP), in patients with ALL/LBL who developed hypersensitivity/silent inactivation to E. coli-derived ASPs, leading to approval of JZP458 by the FDA and EMA. Primary efficacy and safety data have been reported; here, we report on adverse events of interest (AEIs: allergic reaction, pancreatitis, thrombosis, hepatotoxicity) and nausea/vomiting, and summarize post hoc descriptive analyses of AEIs by timing and known risk factors (eg, age and ethnicity). Methods: Each pegylated E. coli ASP remaining on treatment was replaced by 6 doses of JZP458 administered Monday/Wednesday/Friday (MWF). Three intramuscular (IM) cohorts (1a [25 mg/m2 MWF], n=33; 1b [37.5 mg/m2 MWF], n=83; and 1c [25/25/50 mg/m2 MWF], n=51) and 1 intravenous (IV) cohort (25/25/50 mg/m2 MWF, n=61) were evaluated. Results: Rates of any-grade treatment-related allergic reactions, pancreatitis, thrombosis, increased ALT/AST, and increased bilirubin were 11%, 7%, 1%, 16%, and 7% in the total IM cohort and 26%, 5%, 2%, 18%, and 5% in the IV cohort, respectively. Rates of treatment-related grade ≥2 nausea/vomiting (N/V) were 32% and 64% in the total IM and IV cohorts. Table shows the median number of JZP458 doses on or before the first AEI. Notably, rates of grade ≥2 N/V events were similar after 25 and 50 mg/m2 dosing. Subgroup analyses showed no consistent trends in the rates of any-grade AEIs by age except for pancreatitis where rates were numerically higher in patients aged 12 to <18 (9/62 [15%]) and ≥18 years (4/31 [13%]) than in those aged 6 to <12 (1/71 [1%]) or <6 years (1/64 [2%]). Overall, incidences of any-grade treatment-related allergic reactions, pancreatitis, thrombosis, increased ALT/AST, and increased bilirubin among Hispanic patients (n=74) were 12%, 5% 1%, 19%, and 7% respectively, similar to non-Hispanic patients (n=140). Conclusions: The safety profile of JZP458 is consistent with other ASPs in patients with ALL/LBL and generally similar across age and ethnicity subgroups. Clinical trial information: NCT04145531 . [Table: see text]
Source: Journal of Clinical Oncology
Language: English
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
Funder: Jazz Pharmaceuticals
OpenAlex ID: W4399520304