ATLANTA — Asparaginase Erwinia chrysanthemi (marketed as Erwinaze) is well tolerated among children and young adults diagnosed with acute lymphoblastic leukemia (ALL) who have developed hypersensitivity to the Escherichia coli-derived L-asparaginase (L-ASP), according to compassionate use protocol data presented during the 54th American Society of Hematology Annual Meeting and Exposition. L-ASP is part of standard chemotherapy regimens for ALL.
“Erwinaze was well tolerated with no unexpected toxicities identified beyond those associated with L-ASP treatment,” reported lead author Paul V. Plourde, MD, of Jazz Pharmaceuticals in Langhome, PA, and a team of coauthors from several US children’s hospitals. “This is the largest safety study of patients treated with Erwinaze to date.”
Hypersensitivity reactions to E. coli-derived L-ASP can result in anaphylaxis and affect up to 30% of patients, Dr. Plourde reported.
Between February 2006 and November 2011, 940 evaluable patients were dosed Asparaginase Erwinia chrysanthemi at 25,000 IU/m2 on Mondays, Wednesdays and Fridays for 2 consecutive weeks, or replacing planned administrations of E. coli-derived L-ASP after treatment interruption caused by allergic responses. The mean patient age was 9.6 years, and most patients (63%) were boys.
“The majority of patients (74%) completed their planned course of Erwinaze,” Dr. Plourde reported. Allergic hypersensitivity reactions caused discontinuation in 8% of patients.
Of 18 patient deaths during the study, three were deemed “possibly related to study drug”; one case involved fungal infection, one case involved ischemic stroke with streptococcal sepsis, and no cause of death was reported for the third possibly drug-related death.
Grade 3/4 adverse events emerged in 93 patients (9.9%) and included hypersensitivity (3.6%), hyperglycemia (3.5%), anaphylactic reaction (0.9%), pancreatitis (0.9%), thrombosis (0.7%) and liver aminotransferase increases (0.6%); 36% of patients developed one or more treatment-emergent adverse events of any grade, including hypersensitivity (13.9%).
“If patients experience hypersensitivity grade ≥2 in severity, then L-ASP therapy should be discontinued and Erwinaze should be initiated as an alternative therapy,” Dr. Plourde concluded.
Erwinaze has been designated as an orphan drug by the US Food and Drug Administration (FDA), which approved its use with E. coli-hypersensitive ALL patients in November 2011. It can be administered subcutaneously, intramuscularly, or intravenously.
The authors work for Jazz Pharmaceuticals or receive funding from EUSA Pharma, which manufacture and market Erwinaze.