{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T04:51:58Z","timestamp":1792212718358,"version":"4.4.0"},"reference-count":21,"publisher":"American Society of Hematology","issue":"7","license":[{"start":{"date-parts":[[2022,9,15]],"date-time":"2022-09-15T00:00:00Z","timestamp":1663200000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2023,2,16]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>AALL1931, a phase 2\/3 study conducted in collaboration with the Children\u2019s Oncology Group, investigated the efficacy and safety of JZP458 (asparaginase erwinia chrysanthemi [recombinant]-rywn), a recombinant Erwinia asparaginase derived from a novel expression platform, in patients with acute lymphoblastic leukemia\/lymphoblastic lymphoma who developed hypersensitivity\/silent inactivation to Escherichia coli\u2013derived asparaginases. Each dose of a pegylated E coli\u2013derived asparaginase remaining in patients\u2019 treatment plan was substituted by 6 doses of intramuscular (IM) JZP458 on\u00a0Monday\/Wednesday\/Friday (MWF). Three regimens were evaluated: cohort 1a, 25\u00a0mg\/m2 MWF; cohort 1b, 37.5 mg\/m2 MWF; and cohort 1c, 25\/25\/50 mg\/m2 MWF. Efficacy was evaluated by the proportion of patients maintaining adequate nadir serum asparaginase activity (NSAA \u22650.1 IU\/mL) at 72\u00a0hours and at 48\u00a0hours during the first treatment course. A total of 167 patients were enrolled: cohort 1a (n\u00a0= 33), cohort 1b (n\u00a0=\u00a083), and cohort 1c (n\u00a0= 51). Mean serum asparaginase activity levels (IU\/mL) at 72\u00a0hours were cohort 1a, 0.16, cohort 1b, 0.33, and cohort 1c, 0.47, and at 48 hours were 0.45, 0.88, and 0.66, respectively. The proportion of patients achieving NSAA \u22650.1 IU\/mL at 72 and 48\u00a0hours in cohort 1c was 90% (44\/49) and 96% (47\/49), respectively. Simulated data from a population pharmacokinetic model matched the observed data well. Grade 3\/4 treatment-related adverse events occurred in 86\u00a0of\u00a0167\u00a0(51%) patients; those leading to discontinuation included pancreatitis (6%), allergic reactions (5%), increased\u00a0alanine aminotransferase (1%), and hyperammonemia (1%). Results demonstrate that IM JZP458 at 25\/25\/50 mg\/m2 MWF is efficacious and has a safety profile consistent with other asparaginases. This trial was registered at www.clinicaltrials.gov as #NCT04145531.<\/jats:p>","DOI":"10.1182\/blood.2022016923","type":"journal-article","created":{"date-parts":[[2022,9,15]],"date-time":"2022-09-15T21:18:25Z","timestamp":1663276705000},"page":"704-712","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":35,"title":["Recombinant <i>Erwinia<\/i> asparaginase (JZP458) in acute lymphoblastic leukemia: results from the phase 2\/3 AALL1931 study"],"prefix":"10.1182","volume":"141","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8739-9100","authenticated-orcid":false,"given":"Luke","family":"Maese","sequence":"first","affiliation":[{"name":"1Huntsman Cancer Institute, University of Utah, Primary Children\u2019s Hospital, Salt Lake City, UT"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mignon L.","family":"Loh","sequence":"additional","affiliation":[{"name":"2Ben Towne Center for Childhood Cancer Research, Seattle Children\u2019s Research Institute and Department of Pediatrics, Seattle Children\u2019s Hospital, University of Washington, Seattle, WA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mi Rim","family":"Choi","sequence":"additional","affiliation":[{"name":"3Jazz Pharmaceuticals, Palo Alto, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tong","family":"Lin","sequence":"additional","affiliation":[{"name":"3Jazz Pharmaceuticals, Palo Alto, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Etsuko","family":"Aoki","sequence":"additional","affiliation":[{"name":"3Jazz Pharmaceuticals, Palo Alto, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michelle","family":"Zanette","sequence":"additional","affiliation":[{"name":"4Jazz Pharmaceuticals, Philadelphia, PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shirali","family":"Agarwal","sequence":"additional","affiliation":[{"name":"3Jazz 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