Children with acute lymphoblastic leukemia (ALL), the most common form of pediatric cancer, can safely receive intravenous infusions of a reformulated mainstay of chemotherapy that has been delivered via painful intramuscular (IM) injection for more than 40 years, research suggests. This study, the Dana Farber Cancer Institute (DFCI)/ALL Consortium Protocol 05-001, was presented at the 55th annual meeting of the American Society of Hematology (ASH), held December 7-10, 2013, in New Orleans, Louisiana.
Researchers looked at the 4-year, event-free survival and toxicity of Escherichia coli L-asparaginase delivered via IV in its polyethylene glycol (PEG)-conjugated formulation or through IM injection in its native formulation. Clinicians had been delivering the drug via injection because of serious allergic reactions previously linked with IV infusion of the drug in its native form.
The clinical trial is one of the largest to compare the safety, efficacy, and pharmokinetics of the two formulations of the bacteria-based enzyme. Data came from 551 patients, age 1 to 18 years, who were treated for pediatric ALL at 11 centers in the United States and Canada between 2005 and 2010. The findings take on particular relevance now that native L-asparaginase is no longer available in the United States.
“Demonstrating that this important agent can be safely administered intravenously should help to provide clinicians peace of mind that they can decrease patient discomfort without increasing risk,” said Lewis B. Silverman, MD, who presented the data on behalf of the DFCI/ALL Consortium in Massachusetts.
The overall 4-year event-free survival rate for all patients enrolled on the protocol was 86%, among the highest rates ever reported in a pediatric ALL trial. No statistically significant difference in event-free survival occurred between patients in the trial’s IV PEG-asparaginase and IM native L-asparaginase arms (92% and 90%, respectively); nor were there significant differences in the rates of allergic reactions (12% and 9%, respectively), pancreatitis (11% and 9%, respectively), or clotting (6% and 11%, respectively), all of which are potential side effects of L-asparaginase.
PEG-asparaginase remains in the bloodstream longer than L-asparaginase, which means patients can be treated less frequently. The lowest concentrations of drug in the blood of patients in the study’s IV PEG-asparaginase arm were nearly eight times higher than those in the IM-native E coli L-asparaginase group. Also, the pediatric patients experienced less pain and anxiety with IV administration of PEG-asparaginase.
PEG-asparaginase is a modified formulation of E coli-derived L-asparaginase. Previous studies had indicated that PEG-asparaginase may be less allergenic, which suggests that IV administration of the drug might be more feasible than the native E coli preparation.
Protocol 05-001 also investigated an intensified treatment regimen for children with B-cell ALL who showed evidence of high levels of minimal residual disease following initial treatment, who tend to have relatively poor outcomes. The intensified regimen was associated with a 4-year event-free survival rate of 77%, a large improvement over outcomes reported in the past for this group of patients.