The US Food and Drug Administration (FDA) has approved the intravenous administration of asparaginase Erwinia chrysanthemi (Erwinaze).
The product is indicated as a component of a multi-agent chemotherapy regimen to treat patients with acute lymphoblastic leukemia (ALL) who have developed hypersensitivity to E coli-derived asparaginase.
Previously, the only FDA-approved route of administration for asparaginase Erwinia chrysanthemi was through intramuscular injection.
The FDA’s decision to expand the drug’s use was based on a pharmacokinetic study (published in Blood in 2013) of intravenous asparaginase Erwinia chrysanthemi.
The trial included 30 patients with ALL or lymphoblastic lymphoma who developed hypersensitivity (grade ≥ 2) to E coli–derived asparaginase. The patients’ median age was 6.5 years (range, 1-17), 63% were male, and 83% were Caucasian.
Patients received intravenous asparaginase Erwinia chrysanthemi at 25,000 IU/m2/dose, on a Monday/Wednesday/Friday schedule for 2 consecutive weeks (6 doses=1 cycle) for each dose of pegaspargase remaining in their original treatment plan. All other chemotherapy was continued per the original treatment plan.
Before the first dose of intravenous asparaginase Erwinia chrysanthemi, nadir serum asparaginase activity (NSAA) levels were below the limit of quantification (defined as 0.0129 IU/mL) for 91% of patients.
The study’s primary endpoint was the proportion of patients who achieved NSAA ≥ 0.1 IU/mL, which has been associated with complete asparagine depletion, at 48 hours after dose 5 in cycle 1. Nineteen of the 23 evaluable patients (83%) achieved this endpoint.
A secondary objective of the study was to determine the proportion of patients who achieved NSAA ≥ 0.1 IU/mL at 72 hours after dose 6 in cycle 1. Nine patients (45%) achieved this endpoint.
In all 30 patients, the most common asparaginase-related toxicities reported during cycle 1 were hypersensitivity (23%), vomiting (20%), nausea (20%), and hyperglycemia (13%). Pancreatitis and thrombosis each occurred in 3% of patients. One patient experienced a transient ischemic attack.
The most common grade 3 or 4 adverse event was febrile neutropenia (7%). Four patients discontinued treatment before completing cycle 1—3 of them due to hypersensitivity and 1 due to pancreatitis. There were no deaths.
This study was funded by Jazz Pharmaceuticals, the company developing asparaginase Erwinia chrysanthemi.
