Protocol to Reduce Hypersensitivity to Asparaginase Is Not Successful in Pediatric Leukemia/Lymphoma Setting

Among pediatric patients with acute lymphocytic leukemia (ALL) and lymphocytic lymphoma (LL), asparagine depletion with pegasparagase is a common component of treatment; however, up to 24% of patients can experience hypersensitivity reactions. Researchers implemented a premedication protocol to reduce hypersensitivity and found that the addition of a corticosteroid to pegasparagase premedication in patients without a history of reaction may not be beneficial. The results of the study were presented by Jonathan Angus, PharmD, BCOP, and Sarah Menig, PharmD, BCOP, both of Seattle Children’s Hospital, at HOPA’s 16th Annual Conference.

The researchers’ facility implemented a universal pegasparagase premedication with diphenhydramine and hydrocortisone, prolongation of pegasparagase infusion to two hours, and serial serum asparaginase activity (SAA) monitoring.

They conducted a retrospective chart review of children and adolescents with ALL and LL who received their second or later dose of pegasparagase between June 15, 2015, and August 1, 2018. Patients were classified into two groups: preintervention (those who received three or more doses prior to the implementation of the protocol on December 15, 2016; n=65; median age 6.9 years; range, 0.2-21.2 years) and post-intervention (those who received one or two doses after protocol implementation; n=74; median age, 5.0 years; range, 0.4-25.0 years).

Hypersensitivity reactions occurred in 18.5% (n=12) of the preintervention group and 21.6% (n=16) of the post-intervention group (P=0.64). There were no differences in reaction severity between the groups: 83% of preintervention and 63% of post-intervention patients experienced grade 3 hypersensitivity reactions.

Overall, 72 patients had evaluable asparaginase activity levels after at least one treatment dose, and four patients (5.6%) had inadequate SAA levels, two of which were silent inactivation, and two patients experienced hypersensitivity symptoms.

The study is limited by its single center, retrospective design.

“Optimal premedication strategies capable of reducing the incidence of hypersensitivity reactions to pegasparagase should continue to be investigated in order to preserve this essential treatment modality,” the researchers concluded.

Menig S, Angus J, Tucker S, et al. The impact of pegasparagase premedication on hypersensitivity reactions in pediatric acute lymphoblastic leukemia (ALL) and lymphoblastic lymphoma (LL) patients. Presented at HOPA 16th Annual Conference. March 2020, Tampa, Florida.