Intravenous and Intramuscular Administration of Asparaginase in Pediatric Patients with Acute Lymphoblastic Leukemia: Treatment Patterns and Perceptions
Authors: Bernard Celine , Hall Megan P. , Doede Tina 
Published: October 2019

Abstract
Background : Asparaginase is an important component of therapy for acute lymphoblastic leukemia (ALL). In the United States, asparaginase may be administered as a course of intramuscular (IM) injections. These injections can be painful and may cause anxiety in children undergoing chemotherapy treatment for ALL [August KJ, et al. J Pediatr Hematol Oncol. 2013;35(7):e283-e286]. Intravenous (IV) administration of asparaginase may offer a less painful therapeutic option for patients; however, there exist concerns over an increased incidence of infusion-related reactions associated with this administration method compared with IM delivery. The goal of this study was to assess the practices and attitudes of physicians regarding their treatment of pediatric patients with ALL, including the route of administration of asparaginase.
Method : This study consisted of a 30-minute, online, quantitative survey targeting board-certified physicians with 2-30 years in practice. Inclusion criteria required that physicians have spent ≥75% of their time in direct patient care, treat ≥5 pediatric patients with ALL (aged ≤21 years) in a typical month, and have treated at least 80% of patients with ALL with a Children's Oncology Group, Dana Farber, or St Jude protocol in the past year.
Results: Data regarding route of administration were available from 67 of 74 participating physicians; 63 reported this information for PEG-asparaginase and 67 for asparaginase Erwinia chrysanthemi. Responses included some data not aligned with the product label. IV administration was the standard route of administration for 86% (54/63) of physicians using PEG-asparaginase and for 37% (25/67) of physicians using asparaginase Erwinia chrysanthemi. Five percent (3/63) of PEG-asparaginase users and 15% (10/67) of those using asparaginase Erwinia chrysanthemi reported that the route of administration was determined by patient characteristics and situation. Among physicians who preferred IM administration of asparaginase Erwinia chrysanthemi, the most commonly cited reason was standard of practice or protocol (38%, 12/32). Ease of administration (68%, 17/25) was the most commonly reported reason for physicians using IV administration of asparaginase Erwinia chrysanthemi. Of 15 physician responders who have used IV administration of asparaginase Erwinia chrysanthemi for 6 or more months, 67% (10/15) adhered to a 60-minute infusion duration, whereas 27% (4/15) reported using an infusion duration of ≥90 minutes, which is not aligned with the product label. Of those who administered asparaginase for ≥90 minutes, 1 physician reported that this practice reduced the risk of an infusion reaction, 1 reported that it was due to patient preference, and 1 reported that it was the standard infusion time at their institution. Additionally, 1 physician erroneously reported that the infusion time of ≥90 minutes was in line with the product label for asparaginase Erwinia chrysanthemi. Regarding the rate of infusion, 40% (6/15) of physicians reported that they typically start the infusion gradually (at a lower drug delivery rate) before ramping up the infusion speed for the remaining dose; 1 respondent stated that this infusion method was hospital policy, while the other 5 physicians stated that this method improved patient tolerance/less reactions or the ability to better monitor the patients for side effects.
Conclusion: The majority of physicians using asparaginase Erwinia chrysanthemi preferred using IM administration to treat pediatric patients with ALL. Institutional preferences and standard of practice were the most common responses given for using IM administration. Infusion reactions that may occur with IV administration may be attenuated by prolonging the duration of the infusion, which was reported by a number of physicians experienced with IV asparaginase Erwinia chrysanthemi administration.
Support: This study was funded by Jazz Pharmaceuticals.

Disclosures
Bernard: Jazz Pharmaceuticals: Employment, Equity Ownership. Off Label Use: Asparaginase Erwinia chrysanthemi is indicated as a component of a multi-agent chemotherapeutic regimen for the treatment of patients with ALL who have developed hypersensitivity to E. coli-derived asparaginase. It can be administered by intramuscular injection or by intravenous infusion. For intramuscular use, limit the volume of reconstituted asparaginase Erwinia chrysanthemi at a single injection site to 2 mL; if reconstituted dose to be administered is greater than 2 mL, use multiple injection sites. For intravenous use, infuse asparaginase Erwinia chrysanthemi in 100 mL of normal saline over 1 hour.. Hall:Jazz Pharmaceuticals: Employment, Equity Ownership. Doede:Jazz Pharmaceuticals: Employment, Equity Ownership.