Recombinant Erwinia asparaginase (JZP458) in acute lymphoblastic leukemia/lymphoblastic lymphoma (ALL/LBL): Post hoc analysis of adverse events of interest from AALL1931.

person Etsuko Aoki Jazz Pharmaceuticals, Palo Alto, CA info_outline Etsuko Aoki, Luke Devon Maese, Mignon Loh, Shirali Agarwal, Vijayalakshmi Chandrasekaran, Yali Liang, Nalina Dronamraju, Robert Iannone, Lewis B. Silverman, Elizabeth A. Raetz, Rachel Rau

Authors person Etsuko Aoki Jazz Pharmaceuticals, Palo Alto, CA info_outline Etsuko Aoki, Luke Devon Maese, Mignon Loh, Shirali Agarwal, Vijayalakshmi Chandrasekaran, Yali Liang, Nalina Dronamraju, Robert Iannone, Lewis B. Silverman, Elizabeth A. Raetz, Rachel Rau Organizations Jazz Pharmaceuticals, Palo Alto, CA, University of Utah, Primary Children's Hospital, Salt Lake City, UT, Department of Pediatrics and the Ben Towne Center for Childhood Cancer Research, Seattle Children’s Hospital, Seattle, WA, Jazz Pharmaceuticals, Philadelphia, PA, Dana-Farber Cancer Institute, Boston, MA, NYU Langone Medical Center, New York, NY, Department of Pediatrics and the Ben Towne Center for Childhood Cancer Research, Seattle Children’s Hospital, University of Washington, Seattle, WA Abstract Disclosures Research Funding Jazz Pharmaceuticals 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/m 2 MWF], n=33; 1b [37.5 mg/m 2 MWF], n=83; and 1c [25/25/50 mg/m 2 MWF], n=51) and 1 intravenous (IV) cohort (25/25/50 mg/m 2 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/m 2 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. Timing and dose information of treatment-related adverse events. 25/25/50 mg/m 2 MWF IM (n=51) 25/25/50 mg/m 2 MWF IV (n=61) Median (range) doses on/before first event Allergic reactions a 28 (9-64) 6 (1-25) Pancreatitis 12 (6-18) 18 (12-18) Thrombosis - 21 (21-21) ALT/AST/bilirubin increased 7 (4-18) 8 (2-30) Number of grade ≥2 nausea/vomiting events, n (%) n=29 n=104 After 25 mg/m 2 dose 11 (38) 44 (42) After 50 mg/m 2 dose 11 (38) 52 (50) No dose within 7 days 7 (24) 8 (8) a Includes anaphylactic reaction, (drug) hypersensitivity, infusion-related reaction, rash, rash erythematous, rash maculopapular, and urticaria. ALT, alanine aminotransferase; AST, aspartate aminotransferase; IM, intramuscular; IV, intravenous; MWF, Monday/Wednesday/Friday.

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