The Impact of Dynamic Mortality on the Cost-Effectiveness of Axicabtagene Ciloleucel Versus Standard of Care As Second-Line Therapy in Patients With Large B-Cell Lymphoma in France

OBJECTIVES: Axicabtagene ciloleucel (axi-cel) demonstrated superior clinical outcomes compared to standard of care (SoC) in the ZUMA-7 trial (NCT03391466). Given a proportion of patients in both arms will be considered long-term survivors, the mortality risk for these patients should capture improvements in general population mortality over time. The objective was to compare the cost-effectiveness of axi-cel versus SoC in 2L large B-cell lymphoma (LBCL) from a French perspective when using either a static or dynamic approach to modelling background mortality.

METHODS: Cost-effectiveness was assessed using a standard three-state partitioned survival model, over a 50-year time-horizon. Mixture cure models were used to extrapolate ZUMA-7 survival data, where the proportion of cured patients in both arms experienced general population mortality, adjusted with a standardized mortality ratio. General population mortality from INSEE was simulated in two ways: 1) a static approach where age- and sex-specific mortality data from a single year (2020) was used; and 2) a dynamic approach where year-specific projected mortality for the years 2021 to 2070 was used.

RESULTS: When using a static approach to model background mortality, axi-cel was associated with an incremental QALY gain of 1.49 and an incremental cost of €124,950 compared to SoC, resulting in an incremental cost-effectiveness ratio (ICER) of €84,020/QALY. In contrast, applying a dynamic approach led to a 11.7% increase in predicted median OS and a 6.4% increase in incremental QALYs for axi-cel, resulting in a substantial decrease in the ICER (€78,979/QALY).

CONCLUSIONS: Compared to the static approach, using dynamic background mortality resulted in a meaningful reduction in the ICER for axi-cel for 2L LBCL in France. The dynamic approach to modelling should be considered appropriate for French HTA submissions to ensure the impacts of future improvements in health are reflected in estimates of cost-effectiveness.