Study: JZP458 Shows Positive Benefit in Acute Lymphoblastic Leukemia, Lymphoblastic Lymphoma
JZP458, a recombinant Erwinia-derived ASNase from a Pseudomonas fluorescens expression platform, was previously approved by the FDA for patients with ALL/LBL who had developed hypersensitivity to Escherichia coli (E. coli)–derived ASNase.
Results from a recent study of L-asparaginase (ASNase) in patients with acute lymphoblastic leukemia (ALL) or lymphoblastic lymphoma (LBL) demonstrated a positive benefit-risk profile of the intramuscular (IM) JZP458 dosing regimen with a safety profile consistent with other asparaginases, according to a presentation at the 2022 American Society of Clinical Oncology (ASCO) Annual Meeting.
In patients with ALL or LBL, hypersensitivity has been associated with inferior outcomes, which can lead to an inability to receive ASNase therapy. JZP458, a recombinant Erwinia-derived ASNase from a Pseudomonas fluorescens expression platform, was previously approved by the FDA for patients with ALL/LBL who had developed hypersensitivity to Escherichia coli (E. coli)–derived ASNase.
Investigators noted that participant eligibility for the study was base don whether patients had ALL/LBL with less than a grade 3 allergic reaction or silent inactivation to a pegylated E. coli-derived ASNase. For each remaining dose, the pegylated E. coli-derived ASNase was replaced with 6 doses of IM JZP458 on Monday, Wednesday, and Friday (M/W/F) over 2 weeks.
During the trial, 3 dosing cohorts were enrolled in the study, including Cohort 1a at a 25 mg/m2 dose given on M/W/F; Cohort 1b at a 37.5 mg/m2 dose given on M/W/F; and Cohort 1c at a 25 mg/m2 dose given on M/W and 50 mg/m2 given on F. The investigators then defined the results as achieving efficacy based on the proportion of patients who achieved the last 72-hour or 48-hour nadir serum asparaginase activity levels in the first treatment course.
Of the 167 patients enrolled for IM dosing, the median age range was 10 (1, 25) years, whereas the median range of JSP468 courses received was 5 (1, 14) for Cohort 1a, 5 (1, 15) for Cohort 1b, and 4 (1,11) for Cohort 1c. Based on observed data, the proportions of patients achieving NSAA levels ≥0.1 IU/mL at the last 72- and 48-hour period in Cohort 1c during the first course of treatment were 90% (81%, 98%) and 96% (90%, 100%), respectively. Based on modeled data, 92% (91%, 93%) and 94% (93%, 95%) were the proportions achieved.
During the trial, the treatment-related adverse events (TRAEs) that led to discontinuation from the treatment included pancreatitis (6%), drug hypersensitivity (4%), anaphylactic reaction (2%), increased alanine aminotransferase (1%), and hyperammonemia (1%), with no TRAEs leading to death.
Maese LD, Loh ML, Choi MR, et al. Efficacy and safety of intramuscular (IM) recombinant Erwinia asparaginase in acute lymphoblastic leukemia (ALL) or lymphoblastic lymphoma (LBL): The Children’s Oncology Group (COG) AALL1931 study. Accessed June 8, 2022. 10.1200/JCO.2022.40.16_suppl.7001