Session: 614. Acute Lymphoblastic Leukemias: Therapies, Excluding Transplantation and Cellular Immunotherapies: Poster III
Hematology Disease Topics & Pathways:
Lymphoid Leukemias, ALL, Research, clinical trials, Clinical Research, Diseases, Lymphoid Malignancies, emerging technologies, Technology and Procedures
Methods: Eligible patients with ALL/LBL had a grade ≥3 allergic reaction or silent inactivation to a pegylated E. coli-derived asparaginase (PEG). Each remaining dose of PEG was substituted with 6 doses of IV JZP458 over 2 weeks (1 course) at 25/25/50 mg/m2 on Monday/Wednesday/Friday (MWF). Efficacy was assessed by the proportions of patients achieving the last 72- and 48-hour nadir SAA (NSAA) levels ≥0.1 IU/mL during Course 1. A population PK (PopPK) model was also developed for JZP458 based on SAA data.
Results: 61 patients received ≥1 dose of IV JZP458 and were included in this analysis (data cutoff: July 19, 2021). The median (range) age was 10 (1, 24) years. The mean (95% CI) SAA levels (IU/mL) were 0.10 (0.07, 0.13) at 72 hours and 0.25 (0.20, 0.29) at 48 hours. The proportions (95% CI) of patients achieving NSAA levels ≥0.1 IU/mL at 72 and 48 hours in Course 1 were 40% (26%, 54%) and 90% (82%, 98%), respectively. PopPK modeling and simulation suggested that 51% (49%, 54%) and 91% (90%, 92%) of patients would achieve NSAA levels ≥0.1 IU/mL at 72 and 48 hours in Course 1, respectively. Grade 3/4 treatment-related adverse events (TRAEs) occurred in 29 (48%) patients. Incidences of any grade TRAEs of interest were: allergic reactions (23%), hepatotoxicity (11%), pancreatitis (0%), and thrombosis (0%). TRAEs leading to discontinuation occurred in 15 (25%) patients and included hypersensitivity reactions (15%), vomiting (3%), infusion-related reaction (3%), nausea (2%), and hyperammonemic encephalopathy (2%). No TRAEs led to death. The geometric mean half-life for JZP458 was estimated at 19.1 hours and 8.3 hours for IM and IV administration, respectively. PopPK model-based simulation predicted that NSAA levels ≥0.1 IU/mL are best maintained when IV JZP458 is administered at 25 mg/m2 every 48 hours (90% of patients [95% CI: 89%, 92%] at the last 48-hours) or when JZP458 is administered IV at 25 mg/m2 Monday/Wednesday and IM at 50 mg/m2 on Friday due to the longer half-life for IM (92% of patients [95% CI: 91%, 93%] at the last 72-hours; 93% of patients [95% CI: 92%, 94%] at the last 48-hours).
Conclusions: Results from the AALL1931 study demonstrate that IV administration of JZP458 at 25 mg/m2 every 48 hours is feasible and efficacious with a safety profile consistent with other asparaginases. PopPK modeling supports that JZP458 dosing at 25 mg/m2 IV every 48 hours or 25/25/50 mg/m2 IV/IV/IM MWF would achieve sustained asparaginase activity (NSAA levels ≥0.1 IU/mL in ≥90% of patients) thereby providing dosing flexibility to patients and physicians.
Disclosures: Maese: Jazz Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Choi: Jazz Pharmaceuticals: Current Employment, Current equity holder in publicly-traded company. Lin: Jazz Pharmaceuticals: Current Employment, Current equity holder in publicly-traded company. Aoki: Etsuko Aoki: Current Employment, Current equity holder in publicly-traded company. Agarwal: Jazz Pharmaceuticals: Current Employment, Current equity holder in publicly-traded company. Wu: Jazz Pharmaceuticals: Current Employment, Current holder of stock options in a privately-held company. Iannone: Jazz Pharmaceuticals: Current Employment, Current equity holder in publicly-traded company. Silverman: Jazz Pharmaceuticals: Other: Was an employee of Jazz Pharmaceuticals at the time of the study and holds stock ownership and/or stock options in Jazz Pharmaceuticals. Silverman: Jazz Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees; Servier: Membership on an entity's Board of Directors or advisory committees. Raetz: BMS: Other: Data and Safety Monitoring Board; Pfizer: Research Funding. Rau: Jazz Pharmaceuticals: Consultancy, Membership on an entity's Board of Directors or advisory committees; Servier Pharmaceuticals: Consultancy, Membership on an entity's Board of Directors or advisory committees; AbbVie Pharmaceuticals: Other: Spouse is employee and stock holder.