Safety profile of asparaginase Erwinia chrysanthemi in a large compassionate-use trial.

Abstract

BACKGROUND:

L-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 Escherichia coli-derived asparaginase. After hypersensitivity, E. coli-derived asparaginase should be discontinued and an alternative asparaginase preparation, such as asparaginase Erwinia chrysanthemi, may be initiated. We conducted a compassionate-use study to collect additional safety information on asparaginase Erwinia chrysanthemi and to support FDA approval of the product.

PROCEDURE:

Patients with ALL or lymphoblastic lymphoma (LBL; N = 1368) who developed a hypersensitivity reaction (grade ≥2) to an E. coli-derived asparaginase participated in this trial. The recommended asparaginase Erwinia chrysanthemi dose was 25,000 IU/m(2) three days per week (Monday/Wednesday/Friday) for two consecutive weeks for each missed pegylated E. coli-derived asparaginase dose and 25,000 IU/m(2) for each missed nonpegylated asparaginase dose for the completion of their planned asparaginase treatment.

RESULTS:

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 Erwinia chrysanthemi. There was no apparent difference in the incidence of the most commonly reported AEs with asparaginase treatment by age, administration, or disease state.

CONCLUSIONS:

This study further established the safety profile of asparaginase Erwinia chrysanthemi in patients with ALL or LBL who had a hypersensitivity reaction to an E. coli-derived asparaginase.

• Authors: Paul V Plourde, Sima Jeha, Nobuko Hijiya, Frank G Keller, Lewis B Silverman, Susan R Rheingold, ZoAnn E Dreyer, Gary V Dahl, Taheri Mercedes, Chinglin Lai, Tim Corn
• Journal: Pediatric blood & cancer (Pediatr Blood Cancer) Vol. 61 Issue 7 Pg. 1232-8 (Jul 2014) ISSN: 1545-5017 [Electronic] United States
• PMID: 24436152 (Publication Type: Clinical Trial, Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)
• Copyright: © 2014 Wiley Periodicals, Inc.

Chemical References

• Antineoplastic Agents
• Bacterial Proteins
• Recombinant Proteins
• Asparaginase

Topics

• Adolescent
• Adult
• Antineoplastic Agents (administration & dosage, adverse effects)
• Asparaginase (administration & dosage, adverse effects)
• Bacterial Proteins (administration & dosage, adverse effects)
• Child
• Child, Preschool
• Dickeya chrysanthemi (enzymology)
• Dose-Response Relationship, Drug
• Drug Hypersensitivity (etiology, mortality)
• Female
• Humans
• Infant
• Male
• Middle Aged
• Precursor Cell Lymphoblastic Leukemia-Lymphoma (drug therapy, mortality)
• Recombinant Proteins (administration & dosage)