Safety profile of asparaginase Erwinia chrysanthemi in a large compassionate‐use trial. Issue 7 (16th January 2014)

• Record Type: Journal Article
• Authors: Plourde, Paul V.; Jeha, Sima; Hijiya, Nobuko; Keller, Frank G.; Silverman, Lewis B.; Rheingold, Susan R.; Dreyer, ZoAnn E.; Dahl, Gary V.; Mercedes, Taheri; Lai, Chinglin; Corn, Tim
• Is Part Of: Pediatric blood & cancer. Volume 61:Issue 7(2014:Jul.)
• Page Start: 1232
• Page End: 1238
• Publication Date: 2014-01-16
• Subjects: Tumors in children -- Periodicals; Blood -- Diseases -- Periodicals; Cancer in children -- Periodicals; 618.92
• DOI: 10.1002/pbc.24938
• Languages: English
• ISSNs: 1545-5009

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <sec id="pbc24938-sec-0001" sec-type="section"> <title>Background</title> <p> <sc>L</sc>‐Asparaginase is an integral component of standard chemotherapy regimens for the treatment of acute lymphoblastic leukemia (ALL). Clinical hypersensitivity, a common reason for treatment discontinuation, has been reported in 10–30% of patients receiving <italic>Escherichia coli</italic>‐derived asparaginase. After hypersensitivity, <italic>E. coli</italic>‐derived asparaginase should be discontinued and an alternative asparaginase preparation, such as asparaginase <italic>Erwinia chrysanthemi</italic>, may be initiated. We conducted a compassionate‐use study to collect additional safety information on asparaginase <italic>Erwinia chrysanthemi</italic> and to support FDA approval of the product.</p> </sec> <sec id="pbc24938-sec-0002" sec-type="section"> <title>Procedure</title> <p>Patients with ALL or lymphoblastic lymphoma (LBL; N = 1368) who developed a hypersensitivity reaction (grade ≥2) to an <italic>E. coli</italic>‐derived asparaginase participated in this trial. The recommended asparaginase <italic>Erwinia chrysanthemi</italic> dose was 25, 000 IU/m<sup>2</sup> three days per week (Monday/Wednesday/Friday) for two consecutive weeks for each missed pegylated <italic>E. coli</italic>‐derived asparaginase dose and 25, 000 IU/m<sup>2</sup> for each missed nonpegylated asparaginase dose for the completion of their planned asparaginase treatment.</p> </sec> <sec id="pbc24938-sec-0003" sec-type="section"> <title>Results</title> <p>Adverse event reports and/or case report forms were completed for 940 patients. The most common adverse event (AE) was hypersensitivity (13.6%). Eighteen patients (1.9%) died during the study. Most patients (77.6%) completed their planned asparaginase treatment with asparaginase <italic>Erwinia chrysanthemi</italic>. There was no apparent difference in the incidence of the most commonly reported AEs with asparaginase treatment by age, administration, or disease state.</p> </sec> <sec id="pbc24938-sec-0004" sec-type="section"> <title>Conclusions</title> <p>This study further established the safety profile of asparaginase <italic>Erwinia chrysanthemi</italic> in patients with ALL or LBL who had a hypersensitivity reaction to an <italic>E. coli</italic>‐derived asparaginase. Pediatr Blood Cancer 2014;61:1232–1238. © 2014 Wiley Periodicals, Inc.</p> </sec> </abstract>