Economic Burden Associated with Switching to Second Line Asparaginase (Recombinant Erwinia) in Pediatrics, Adolescents and Young Adults (AYA) with Acute Lymphoblastic Leukemia (ALL)
Authors: McCormick Meghan , Gu Tina , Bhagnani Tarun , Chatterjee Indrani , Prashar Arun , Potluri Ravi , Papademetriou Eros , Maese Luke 
Published: December 2024

Background: Long-acting asparaginases derived from E. coli (pegaspargase [PEG] and calaspargase pegol [CAL-PEG]) are critical components of frontline (1L) chemotherapy regimens in pediatrics, adolescents and young adults (AYA) with acute lymphoblastic leukemia (ALL). In the event of ≥grade 3 hypersensitivity reactions based on CTCAE version 5.0, to an E. coli asparaginase, patients often switch to second line (2L) asparaginase derived from Erwinia (Recombinant Erwinia), which has an increased dosing of thrice/week due to its shorter half-life. Infusion reactions may masquerade as hypersensitivity reactions, leading to unnecessary formulation switches and potentially increased economic and healthcare burdens on patients and the healthcare system. Formulation switches may be mitigated through therapeutic drug monitoring (TDM) utilization which may help differentiate between neutralizing and non-neutralizing antibody-mediated reactions through quantification of serum asparaginase activity levels. This study aims to quantify the costs and healthcare resource utilization (HRU) associated with switching from 1L to 2L asparaginases in pediatrics and AYA patients with ALL, overall and by use of TDM.
Methods: This is a retrospective study using Optum's deidentified Clinformatics® data mart. Pediatric/AYA patients (&lt;40 years) diagnosed with ALL between Jan. 2021 and Sep. 2023 and treated with frontline asparaginase-containing regimen were identified throughout the US. Treatment start date was designated as the index date. Descriptive analyses were used to assess baseline demographics in the pre-index period, and use of premedication, TDM and proportion of switchers to recombinant Erwinia in the follow-up (post-index) period. Annualized mean HRU and costs were compared in the follow-up period between switchers and non-switchers, and by use of TDM in terms of inpatient admissions, outpatient visits, emergency department (ED) visits, and medical and prescription drugs. Among switchers, HRU and costs were also compared pre- and post-switching. Costs were adjusted and inflated to 2023 dollars.
Results: A total of 154 pediatric or AYA patients with ALL were identified, of which 116 received PEG and 38 received CAL-PEG. Median (IQR) age was 8 (6-15) years. No patient &gt;22 years received CAL-PEG, while 11% of patients receiving PEG were &gt;22 years old. Nearly two-third were male. Median (IQR) follow-up duration was 11.3 (6-19.4) months. Approximately 58% of patients were given premedication- all on the same day as PEG/CAL-PEG infusion; 40% had TDM performed, 25% had both and 29% had none. Overall, 35 of 154 patients (23%) switched to recombinant Erwinia; including 21% of those on PEG and 29% of those on CAL-PEG. Switchers had a significantly higher mean outpatient visits per year compared to non-switchers (83 vs. 72; p=0.0466). This was mainly driven by the increased visits associated with recombinant Erwinia administration vs PEG/CAL-PEG administration (mean # of visits: 18 vs. 3, respectively; p&lt;0.0001). Mean total healthcare costs were three times higher in switchers than non-switchers ($1,272,846 vs. $467,773; p&lt;0.0001). This was mainly driven by outpatient costs which were nearly four times higher in switchers than non-switchers ($1,094,941 vs. $286,243). ED costs were higher for switchers ($11,960 vs $8,930), while outpatient prescription costs were lower ($5,273 vs $9,416) (all p&lt;0.0001). No significant differences were found for inpatient costs. Among switchers, the outpatient costs were higher post-switching compared to pre-switching ($1,130,975 vs. $528,237; p&lt;0.0001) further suggesting that the majority of the higher costs in the switchers was driven by administration of recombinant Erwinia. When compared by use of TDM, 28% switched to recombinant Erwinia in the non-TDM group and 14.8% in the TDM group. Mean outpatient costs were $511,810 and $384,396 (p&lt;0.0001) in the non-TDM and TDM groups, respectively.
Conclusions: Switch from 1L asparaginase to 2L recombinant Erwinia is relatively common in pediatric and AYA ALL patients which significantly increases treatment costs and HRU, mainly driven by higher outpatient medical costs of recombinant Erwinia. Consideration should be given to performing TDM which may have important implications for mitigating unnecessary switches as well as reducing healthcare burden and achieving substantial cost savings for payers.