OBJECTIVES: Chimeric Antigen Receptor T-cell (CAR-T) therapy is a promising treatment option for patients with relapsed or refractory (R/R) large B-cell lymphoma (LBCL). However, its high costs raise concerns. The objective of this study was to evaluate the cost-effectiveness of two CD19-directed CAR-T products, axicabtagene ciloleucel (axi-cel) and tisagenlecleucel (tisa-cel), and the impact of country settings and performance-based managed entry agreements (MEAs).

METHODS: Decision-analytic modeling was used to compare the cost-effectiveness of axi-cel and tisa-cel with the prior standard of care for adult patients with R/R LBCL after two or more lines of systemic therapy from the perspectives of the Dutch and UK healthcare settings. The model estimated total costs, effects (life years and quality-adjusted life years (QALYs)) and incremental cost-effectiveness ratios (ICERs). Sensitivity and scenario analyses were conducted to assess uncertainties and the impact of performance-based MEAs

RESULTS: Both CAR-T products provided substantial health benefits but came with significant costs. In the Dutch setting, the estimated discounted ICERs were €127,191/QALY for axi-cel and €141,939/QALY for tisa-cel. In the UK setting, the corresponding discounted ICERs were £94,880/QALY for axi-cel and £118,275/QALY for tisa-cel. However, the interventions were not considered cost-effective based on the willingness-to-pay thresholds in both countries. Axi-cel consistently showed better cost-effectiveness than tisa-cel across the country settings, and the ICERs in the UK were more favorable. Incorporating performance-based MEAs improved the cost-effectiveness of both CAR-T products, but did not result in cost-effective ICERs.

CONCLUSIONS: The lack of cost-effectiveness was mainly due to the high costs of both CAR-T products. Axi-cel's superior cost-effectiveness was attributed to its greater health benefits. Incorporating performance-based MEAs improved cost-effectiveness in both countries, suggesting their importance in evaluating the cost-effectiveness of these therapies. Differences among countries were primarily influenced by differences in discount rates and perspectives in health technology assessment.