L-Asparaginase (L-ASP) Related Toxicities with Asparaginase Erwinia Chrysanthemi in a Large Compassionate Use Protocol.
Authors: Plourde Paul V. , Jeha Sima , Hijiya Nobuko , Keller Frank G , Rheingold Susan R. , Dreyer Zoann E. , Dahl Gary V. , Mercedes Taheri , Corn Tim 
Published: October 2019

Abstract
Abstract 2568

Background:
L-asparaginase (L-ASP) is an important component of multi-agent chemotherapy for treatment of Acute Lymphoblastic Leukemia (ALL) in children and young adults. The pegylated E. coli derived form, Oncaspar® (PEG-ASP), is most commonly used because of its longer half-life and lower immunogenicity compared to the native enzyme; however, clinical hypersensitivity reactions still occurs in 10–30% of patients (pts) requiring its discontinuation. Asparaginase Erwinia Chrysanthemi (Erwinaze™) is an L-ASP derived from a different bacterium and is immunologically distinct from the E. coli L-ASP. We conducted a compassionate use trial of Erwinaze in pts with ALL and hypersensitivity to native E. coli or PEG-ASP to collect safety information.

Patients and Methods:
Pts of any age with ALL or lymphoblastic lymphoma (LBL) who developed a Grade ≥2 clinical hypersensitivity reaction to PEG-ASP or native E. coli ASP (Elspar®) were eligible. Pts with a history of pancreatitis, previous allergic reaction to Erwinaze, or pregnant, were excluded. The study was IRB approved at each institution and pts/family provided informed consent/assent. Safety information on Erwinaze-related adverse events (AEs) were captured on Case Report Forms (CRFs) submitted to the Sponsor when the pt completed his/her entire Erwinaze treatment plan. AEs may have also been reported directly by the investigational sites.

Results:
Between February 2006 and November 2011, 1,368 pts were treated with Erwinaze. CRFs were received in 893 pts and 47 additional AEs were received from patients for which a CRF was not obtained. The average age was 9.6 years (range 1–66). The majority of patients (63.5%) were male. Of the pts for which CRFs were received (893); 77.6% were able to conclude their Erwinaze treatment. Discontinuation was due to allergic reaction in 8.8%; other AEs 4.7%; at the physician or patient discretion 7.5%; and missing information in 1.3%. Anaphylaxis was reported in 8 pts (0.9%) and Grade ≥2 clinical hypersensitivity reactions in 130 (13.8%). The incidence of pancreatitis was 3.9%, hemorrhagic or thrombosis abnormalities 2.4%, hyperglycemia 3.6% and elevation in liver enzymes 3.5%. There were 18 deaths on study; 11 disease progression, 3 intracranial hemorrhage, 4 other individual reports.

Conclusion:
This is the largest study of pts treated with Erwinaze to determine the toxicity profile. Erwinaze was well tolerated with no unexpected toxicities identified beyond those associated with L-Asp treatment. This compassionate use trial permitted the continuation and completion of asparaginase treatment in 77.6% of pts with hypersensitivity reactions to E. coli formulations. Final results will be available for presentation.

Disclosures:
Plourde: Jazz Pharmaceuticals: Employment, Equity Ownership. Mercedes:Jazz Pharmaceuticals: Employment. Corn:EUSA Pharma: Employment.