Authors' objectives: The Academic Technology Assessment Group (ATAG) reviewed a report submitted by the manufacturer of epcoritamab (Genmab K.K.) on the additional benefits and cost-effectiveness of epcoritamab in comparison with the salvage chemotherapy for patients with relapsed or refractory large B-cell lymphoma who had received at least two prior lines of therapy, including an anti-CD20 monoclonal antibody. This report summarises the results of a review and reanalysis conducted by the ATAG. In assessing the additional benefits of epcoritamab, the manufacturer primarily based its arguments on the results of a Matching-Adjusted Indirect Comparison (MAIC) using individual patient data from the EPCORE NHL-1 trial and aggregate data from the SCHOLAR-1 trial. The manufacturer argued the additional benefits of epcoritamab based on the MAIC analysis, which indicated that epcoritamab had a statistically significant effect on overall survival (OS) relative to salvage chemotherapy. The ATAG accepted the manufacturer's arguments of additional benefits based on these results while acknowledging several methodological challenges, including the high uncertainty associated with unanchored MAIC, biases inherent in single-arm trial designs, and strong assumptions regarding effect modifiers and prognostic factors. For the cost-effectiveness analysis, the manufacturer employed a Partitioned Survival Analysis (PartSA) model consisting of three health states: progression-free survival (PFS), post-progression survival (PPS), and death. The R-ICE regimen was selected as the least expensive salvage chemotherapy regimen for comparison. The manufacturer's model assumed that patients who maintained PFS for three years would achieve long-term remission, and patients in long-term remission would have utility values equivalent to those of the general population. The ATAG determined that these assumptions might not accurately reflect clinical reality and modified the analysis by setting the utility value for long-term remission equal to the PFS state utility and adopting a mixture-cure model for survival curve extrapolation. The ATAG base-case analysis showed that epcoritamab incurred additional costs of JPY 40,291,857 and conferred an additional 4.006 quality-adjusted life years (QALYs) relative to salvage chemotherapy. These findings resulted in an incremental cost-effectiveness ratio (ICER) of JPY 10,058,394 per QALY gained. Scenario analyses using different survival curve models, including log-normal and AICaveraged models, yielded ICERs of JPY 11,108,558/QALY and JPY 11,340,614/QALY, respectively, confirming the robustness of the results. While acknowledging the methodological limitations of indirect comparison via MAIC and uncertainties in effect estimation, these results suggest that the ICERs for epcoritamab relative to salvage chemotherapy were likely to fall within the range of JPY 7.5?11.25 million per QALY from the perspective of public healthcare payers in Japan. Additionally, as instructed by the expert committee, a cost-minimisation analysis comparing epcoritamab with polatuzumab vedotin in combination with bendamustine and rituximab (Pola-BR) was conducted, showing that epcoritamab incurred additional costs of JPY 25,145,483 relative to Pola-BR.

Project Status: Completed

URL for project: https://c2h.niph.go.jp/

Year Published: 2025

URL for published report: https://c2h.niph.go.jp/results/C2H2307.html

English language abstract: An English language summary is available

Publication Type: Not Assigned

Country: Japan

Organisation Name: Center for Outcomes Research and Economic Evaluation for Health

Contact Address: 2-3-6 Minami, Wako-shi, Saitama 351-0197 Japan

Contact Name: Takeru Shiroiwa

Contact Email: t.shiroiwa@gmail.com