Premedication prior to PEG‐asparaginase is cost‐effective in pediatric patients with acute lymphoblastic leukemia

Abstract

Background: PEG-asparaginase is critical in pediatric acute lymphoblastic leukemia (ALL) therapy but is highly immunogenic. Severe allergic reactions lead to substitution of further PEG-asparaginase with Erwinia. Erwinia is associated with more frequent dosing, increased expense, and limited availability. Premedication may reduce rates of allergic reactions.Procedures: This Markov model evaluated the cost-effectiveness of three strategies: premedication plus therapeutic drug monitoring (TDM), TDM alone, and no premedication or TDM. We modeled two scenarios: a standard-risk (SR) B-ALL patient receiving two asparaginase doses and a high-risk (HR) patient receiving seven asparaginase doses. The model incorporated costs of asparaginase, premedication, TDM and clinic visits, and lost parental wages associated with each additional Erwinia dose. We incorporated a five-year time horizon with a societal perspective. Outcomes were Erwinia substitutions avoided and differences in quality-adjusted life years (QALYs). Probabilistic and one-way sensitivity analyses evaluated model uncertainty. Results:In both scenarios, premedication was the least costly strategy. In SR and HR scenarios, premedication with monitoring resulted in 8% and 7% fewer changes to Erwinia compared with monitoring alone and 3% and 2% fewer changes compared with no premedication/monitoring, respectively. Premedication resulted in the most QALYs gained in the SR patients. Individual variation of model inputs did not change premedication/monitoring favorability for either scenario. In probabilistic sensitivity analyses, premedication/monitoring was favored in >87% of iterations in both scenarios. Conclusion:Compared with other strategies, premedication use and asparaginase level monitoring in children with B-ALL is potentially cost-saving.

L-Asparaginase Toxicity in the Treatment of Children and Adolescents with Acute Lymphoblastic Leukemia

“…Furthermore, premedication in patients who have already experienced a hypersensitivity reaction may not protect against a further hypersensitivity [28]. However, a recent study by McCormick et al illustrated that the use of premedication prior to PEG-asparaginase combined with asparaginase level monitoring is the most cost-effective approach in both standard and high risk pediatric ALL patients with 8% and 7% fewer changes to Erwinia-derived asparaginase compared to using monitoring without premedication [29].…”

“…In our study, all 40 patients who had clinical hypersensitivity discontinued native E. coli L-asparaginase. Most of them (29) switched to another type (Erwinia-derived asparaginase or PEG-asparaginase), but 11 patients did not receive any type of asparaginase preparation after the allergic episode. Among the 11 patients who discontinued asparaginase, seven had a cumulative dose ≥50% of the scheduled dose.…”

Asparaginase activity monitoring in pediatric acute lymphoblastic leukemia: A cross‐sectional nationwide study in Spain

“…However, premedication use and asparaginase level monitoring may contribute to prevent adverse events, drug substitutions, and may be cost-effective in pediatric ALL. 35,36 Results of the present study should be interpreted taking into account the observational characteristics of the survey based on selfreporting. However, the number of participants with solid experience in the management of pediatric cancer and accounting for 90% of hospitals in which children with ALL are treated in Spain, ensures that the survey was able to capture real-world data of asparaginase activity monitoring in clinical practice.…”

Current Use of Asparaginase in Acute Lymphoblastic Leukemia/Lymphoblastic Lymphoma

“…Timing of administration with continuous periods of exposure with less gaps in treatment are associated with lower rates of hypersensitivity (52,54). Various reports of mitigation techniques, including pretreatment with corticosteroids and antihistamines exist, many with mixed results (55)(56)(57)(58). However, with limited downside premedication has become common practice in many institutions.…”