L-asparaginase (L-ASP)-related toxicities with Erwinia L-ASP in a large compassionate-use protocol.

Abstract

9534 Background: L-ASP is an important component of the multi-agent chemotherapy in children and young adults for treatment of acute lymphoblastic leukemia (ALL). The pegylated E. coli derived form, Oncaspar (PEG-ASP) is most commonly used because of its longer half-life; however, clinical hypersensitivity reactions can occur in 10-30% of patients requiring its discontinuation. Erwinia L-ASP (E) 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 E in patients with ALL and hypersensitivity to PEG-ASP to collect safety information. Methods: Patients were ≥ 1 year of age with ALL who developed a clinical hypersensitivity reaction to PEG-ASP. Patients with a history of pancreatitis, previous allergic reaction to E, or pregnant, were excluded. E was administered at 25,000 IU/m2 IM/IV/SC 3 times per week on a Monday/Wednesday/Friday schedule for 2 weeks to replace each dose of PEG-ASP. The study was IRB approved at each institution and patients/family provided informed consent. Safety information on E-related adverse events (AEs) was captured on Case Report Forms (CRFs) submitted to the Sponsor when the patient completed his/her entire E treatment plan. Results: Between February 2006 and April 2010, 569 patients were treated with E and had CRFs completed. The average age was 9.4 years (range 1-66). The majority of patients (61.2%) were male. 13.9% of patients withdrew due to AEs, 7.6 % due to allergic reactions. Anaphylactic and hypersensitivity reactions were reported in 6.5% and 4.6% respectively. The incidence of pancreatitis was 2.5% thromboembolic disorders 1.3%, hyperglycemia 1.4% and elevation in liver enzymes 1.6%. There were 5 deaths on study (4 relapses, 1 thromboembolic event). Conclusions: This is the largest study of patients treated with E to determine the toxicity profile. E was well tolerated with no unexpected toxicities identified. This compassionate use trial showed E was well tolerated and permitted continued asparaginase treatment in 85% of patients with hypersensitivity reactions to E.coli formulations. Updated data will be presented.