Cost-Effectiveness of Treatment of Childhood Acute Lymphoblastic Leukemia with Pegasparaginase and Erwinia Asparaginase: The Impact of Expensive Chemotherapy
Authors: Tong Wing H. , van der Sluis Inge M. , Alleman Cathelijne , van Litsenburg Raphaele RL , Kaspers Gertjan , Pieters Rob , Uyl-de Groot Carin A. 
Published: October 2019

Abstract
Abstract 4227
Asparaginase is an expensive drug, but important in childhood acute lymphoblastic leukemia (ALL). Due to increasing costs of treatment of childhood ALL more insight in costs of asparaginase preparations is desired. In order to compare pharmacoeconomic aspects of PEGasparaginase, Erwinia asparaginase and native E.coli asparaginase, we performed a cost-effectiveness analysis in Dutch Childhood Oncology Group (DCOG) ALL-10 medium risk group (MRG) intensification protocol.
Between April 2005 and October 2009, MRG patients were included in this multi-center study. Treatment costs were calculated based on patient level data of 84 subjects (33 female), and were related to allergy to asparaginase. We have used 3 treatment scenarios for asparaginase of which 2 scenarios were hypothetical: PEGasparaginase as first line preparation and Erwinia asparaginase as second line used as scenario 1 (similar to the actual ALL-10 treatment schedule); native E.coli asparaginase as first line preparation and Erwinia asparaginase as second line used as hypothetical scenario 2; or native E.coli asparaginase as first line preparation, PEGasparaginase as second line and Erwinia asparaginase as third line preparation used as hypothetical scenario 3. Medical technology assessments techniques were used for this cost-effectiveness analysis. Decision tree analysis was used to compare costs of PEGasparaginase or Erwinia asparaginase to native E.coli asparaginase, while taking into account the incidence of allergy to asparaginase and the different associated costs. Sensitivity analyses (one-way and two-way) were conducted to account for uncertainty in the used prices and calculated costs.
The total costs of the ALL-10 MRG intensification course of 30 weeks were $71,147 per patient. Subgroup analysis revealed that the costs were $57,893 in patients without PEGasparaginase allergy (N=64). The costs were significantly higher ($113,558) in case of PEGasparaginase allergy (N=20) necessitating a switch to Erwinia asparaginase. The total costs were also calculated based on two weeks of asparaginase exposure; in case of PEGasparaginase the costs were $ 1,930 and for Erwinia asparaginase $ 3,785 per two weeks of treatment.
Decision tree analysis showed that the treatment costs were $ 70,402 when using native E.coli asparaginase as first line preparation in intensification (scenario 3) and $ 71,809 when using PEGasparaginase as first line preparation (scenario 1). Treatment costs using native E.coli asparaginase as first line followed by Erwinia asparaginase as second line (scenario 2) the costs would be significantly higher ($ 103,474). One-way sensitivity analysis showed that the subgroup with allergy to native E.coli asparaginase (scenario 2) had the largest range in treatment costs. When treatment costs were calculated with the new European price of Erwinia asparaginase (the price has been doubled in March 2011), both treatments with PEGasparaginase as first line preparation (scenario 1) or native E.coli asparaginase as first line preparation (scenario 3) would be less expensive ($ 100,199 or $ 103,089, respectively) compared to the native E.coli asparaginase scenario 2 ($ 190,284). Two-way sensitivity analysis revealed that treatment with PEGasparaginase (scenario 1) is less expensive than treatment with native E.coli asparaginase (scenarios 2) for allergy probabilities of PEGasparaginase ranging from zero to 0.8 with a fixed allergy rate of 0.65 (Veerman et al. (Lancet Oncol. 2009)). This also holds true if a fixed allergy rate for native E.coli asparaginase of 0.4 is used, which is frequently found in studies using less native E.coli asparaginase in intensification after native E.coli asparaginase in induction (Nachman et al. (JCO 1997) and Willer et al. (Blood 2011)).
In conclusion, treatment with native E.coli asparaginase, followed by a switch to PEGasparaginase, and subsequently to Erwinia asparaginase in case of allergy carried similar overall costs compared to the treatment with PEGasparaginase as first line drug (followed by Erwinia asparaginase in case of allergy). However, PEGasparaginase is preferred, because it is administered less frequently, with less outpatient care visits and is less immunogenic compared to native E.coli asparaginase. The costs with PEGasparaginase are much lower compared to Erwinia asparaginase.

Disclosures:
No relevant conflicts of interest to declare.