Cost-effectiveness analysis of mosunetuzumab compared with novel alternative immunotherapies in patients with third-line or later relapsed/refractory follicular lymphoma in Japan Free

Follicular lymphoma (FL), a common indolent non-Hodgkin's lymphoma (NHL), accounts for approximately 10-20% of all NHLs. Mosunetuzumab, a CD20×CD3 T-cell-engaging bispecific antibody, redirects T cells to eliminate malignant B cells. In December 2024, mosunetuzumab was approved in Japan for use in adult patients with relapsed or refractory (R/R) FL who have received two or more prior systemic therapies. Other novel immunotherapies such as bispecific antibodies (i.e., epcoritamab) and chimeric antigen receptor-T cell (CAR-T) therapies (i.e., tisagenlecleucel, lisocabtagene maraleucel) have also been approved in Japan for such patients. Though these therapies show promising clinical outcomes, cost-effectiveness is an important issue for these novel approaches, but this depends on each country/region. Therefore, this study aimed to evaluate the cost-effectiveness of mosunetuzumab compared with these new immunotherapies for R/R FL in Japan.

The cost-effectiveness of mosunetuzumab for R/R FL patients was evaluated using a three-health state-partitioned survival model, including progression-free survival (PFS), post-progression survival (PPS), and death. The comparators were epcoritamab, tisagenlecleucel, and lisocabtagene maraleucel, which are immunotherapies with high promise as novel modalities among the regimens used in 3^rd-line FL treatment in Japan.

Efficacy data for mosunetuzumab were from the pivotal phase I/II GO29781 trial. The relative efficacy of mosunetuzumab vs. the comparators was estimated from indirect treatment comparisons due to a lack of a comparator arm in the study. Time to off treatment (TTOT) dictated the proportion of patients who were progression-free and on vs. off treatment at each model cycle. For mosunetuzumab, survival analysis using clinical trial data estimated TTOT. For epcoritamab, TTOT was set equal to the selected parametric distribution for PFS as a proxy due to the lack of data. CAR-T therapies were administered as one-off treatments at the beginning of the model.

Health outcomes were quantified in quality-adjusted life years (QALYs). Health state utilities were derived from the EuroQol 5 Dimension-5 Level (EQ-5D-5L) data collected in the GO29781 study.

The analysis was conducted from the public healthcare payer's perspective and only included direct medical costs: administration costs, management costs for grade 3 or higher adverse events and cytokine release syndrome of any grade, routine care costs, post-progression treatment costs, and end-of-life treatment costs.

Costs were based on the 2025 Japanese fee schedule and drug tariffs, each defined by the Ministry of Health, Labour and Welfare Japan, at an exchange rate of USD 1 = JPY 145 (July 2025). Costs and QALYs were discounted at 2% per year. Cost-effectiveness was assessed using the incremental cost-effectiveness ratio (ICER), and the ICER threshold value was defined as 7.5 million yen / QALY from the price adjustment threshold in the Japanese heath technology assessment.

In the comparison with epcoritamab, a cost-minimization analysis was performed as one of the scenario analyses that compared only the costs with the same treatment effect, because it was assumed that the treatment effect of epcoritamab and mosunetuzumab would be similar. The estimated mean overall survival period for mosunetuzumab and epcoritamab was 12.5 (median: 8.9) years, whereas the PFS state was 4.8 (median: 1.5) years, and the PPS state was 7.64 years. The mean duration of treatment was 5.8 (median: 5.3) months for mosunetuzumab and 57.7 (median: 18.4) months for epcoritamab.

The analysis suggested cost savings for mosunetuzumab compared with epcoritamab. One contributing factor of this cost saving was the difference in total lifetime drug costs, which were JPY 25 million (USD 171,024) for mosunetuzumab and JPY 94 million (USD 644,983) for epcoritamab, with a difference between mosunetuzumab and epcoritamab of JPY 69 million (USD 473,959).

Mosunetuzumab has the potential to be less costly than epcoritamab. The duration of drug administration, a fixed duration for mosunetuzumab and until disease progression for epcoritamab, might drive the cost reduction. Further analyses in comparison with other modalities such as CAR-T therapies, which include costly supportive agents for adverse events, are warranted.