A Cost-Effectiveness Analysis of Axicabtagene Ciloleucel Versus Epcoritamab in Third-Line Diffuse Large B-Cell Lymphoma Patients in the United States

Introduction New immunotherapies have been introduced over recent years that have improved the outlook for relapsed and refractory (r/r) diffuse large B-cell lymphoma (DLBCL). Two classes of these new treatments include chimeric antigen receptor T-cell (CAR-T) and the T-cell engaging bispecific antibodies (BsAbs). Axicabtagene ciloleucel (axi-cel), a CAR-T, was first approved for treatment of r/r DLBCL in 2017 and has follow up data to 5 years demonstrating a durable response while epcoritamab, a BsAbs, received accelerated FDA approval in 2023 but survival data are immature. Objectives We developed a patient-level microsimulation model to compare the cost effectiveness of axi-cel versus epcoritamab in third line (3L) DLBCL. Methods A discrete event simulation was used to simulate lifetime health and economic outcomes after initiation of either axi-cel or epcoritamab in 3L+ DLBCL patients. For both treatments, mixture cure models (MCM) were used in a naïve comparison to extrapolate 3L survival data from ZUMA-1 and EPCORE NHL-1 respectively. Considerable uncertainty surrounds the durability of epcoritamab response. The modeled cure fraction (10%) was chosen such that the predicted overall survival data best fit the overall survival data from EPCORE NHL-1. A United States (US) payer perspective was used. Treatment data and costs were sourced from the available literature and Micromedex and inflated to 2023 US prices. Epcoritamab was strictly modeled as treat to progression, but this assumption was varied in scenario analyses. Costs and utilities were discounted at 3.0% annually. Results In the base case, the axi-cel arm had discounted costs of $508,332 compared to the epcoritamab arm's $685,942. Due to the higher projected survival and duration of progression-free disease in the axi-cel arm, the discounted quality-adjusted life year (QALYs) were higher for axi-cel compared to epcoritamab (4.46 versus 1.88). Axi-cel is therefore both more effective and less costly than epcoritamab due to the high costs accrued for the epcoritamab patients in sustained remission having to undergo costly ongoing treatment, making axi-cel a dominant treatment option. In a scenario analysis, the maximum treatment duration for epcoritamab was restricted to 2 years which resulted in an incremental cost effectiveness ratio for axi-cel of $56,823 which is well below common cost-effectiveness thresholds in the US. Conclusion This simulation suggests that axi-cel is highly cost-effective compared to epcoritamab in a 3L DLBCL setting based on extrapolation of the pivotal trial data. The higher lifetime treatment cost with epcoritamab suggests a treat to progression strategy would result in higher costs over time than the upfront costs of axi-cel and still result in inferior long-term clinical outcomes overall. Future research is needed to confirm these findings in larger samples with longer follow-up.