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/m2 three days per week (Monday/Wednesday/Friday) for two consecutive weeks for each missed pegylated E. coli‐derived asparaginase dose and 25,000 IU/m2 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. Pediatr Blood Cancer 2014;61:1232–1238. © 2014 Wiley Periodicals, Inc.

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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.

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7097 Background: The AYA population is usually defined as pts aged 16 to 39 years. NCCN guidelines recommend that AYA patients with acute lymphoblastic leukemia (ALL) be treated with ‘pediatric-inspired’ protocols that includeL-asparaginase (L-ASP) as an integral component of their multiagent chemotherapy regimen. Hypersensitivity reaction is the most common toxicity associated with L-ASP treatment, occurring in 10%–30% of pts treated with E coli–derived L-ASP, necessitating its discontinuation. In those pts, it is recommended that L-ASP derived from Erwinia chrysanthemi (Erw) be initiated since it is immunologically distinct from E coli–derived L-ASP. Methods: A large compassionate-use trial in pts with ALL or lymphoblastic lymphoma who developed a hypersensitivity reaction (ie, grade ≥2) to an E coli–derived L-ASP was conducted to evaluate the safety of Erw. Pts were excluded if they had a history of pancreatitis, previous allergic reaction to Erw, or were pregnant. Adverse events (AEs) and/or case report forms were completed for 940 pts. The Erw safety information for the full study population was previously reported. Here, we report a safety analysis of pts aged ≥16 years with the majority being AYA (94%), a population in which little Erw safety information has been presented. Results: In this compassionate-use trial, 156 pts were aged ≥16 years. These pts were primarily male (67.9%), had nonrelapsed disease (70.5%), B-lineage ALL (71.2%), and received intramuscular Erw (85.9%). 71.8% completed their planned Erw course. Reasons for discontinuation included allergic reaction (3.2%), other AEs (9.6%), other reasons (6.4%), and unknown reasons (9%). Hypersensitivity occurred in 20 (12.8%); hyperglycemia, 9 (5.8%); pancreatitis, 6 (3.8%); thrombosis, 5 (3.2%); bleeding, 1 (1%). Grade 3/4 AEs with a >5% incidence included hyperglycemia (5.8%). There were 10 deaths: 4 disease progression, 3 infection, 1 coma, 1 renal impairment, 1 unknown. Conclusions: The safety profile of Erw in pts ≥16 years was consistent with the profile in the entire study population. This compassionate-use trial permitted the completion of L-ASP in 71.8% of AYA and adult pts. Clinical trial information: NCT00693602.