Mosunetuzumab is Cost-Effective Compared with Alternative Novel Treatment Options in Patients with Third-Line or Later Relapsed/Refractory Follicular Lymphoma Over a Long-Term Horizon in the United States

Background: Several novel treatment options for third-line or later (3L+) relapsed/refractory (R/R) follicular lymphoma (FL) have been approved by the United States (US) Food and Drug Administration since 2020, contributing to the evolution of the treatment landscape. Treatments include: an enhancer of zeste homolog 2 inhibitor (tazemetostat); chimeric antigen receptor-modified T-cell therapies (axicabtagene ciloleucel [axi-cel], lisocabtagene maraleucel [liso-cel], tisagenlecleucel [tisa-cel]); a bispecific antibody (mosunetuzumab); and a Bruton's tyrosine kinase inhibitor combination (zanubrutinib-obinutuzumab [ZO]). However, data remain limited on the long-term value of mosunetuzumab versus (vs) alternative treatment options. The aim of this study was to quantify the long-term value of mosunetuzumab, in terms of cost-effectiveness, compared with alternative treatment options from a US payer perspective.

Methods: A partitioned survival model was simulated, based on 3 health states: progression-free survival (PFS), post-progression survival, and death. Due to the lack of long-term follow-up data, several parametric fit approaches were considered to extrapolate outcomes from each treatment's pivotal trial (i.e. E7438-G000-101 for tazemetostat [NCT01897571]; ZUMA-5 for axi-cel [NCT03105336]; TRANSCEND FL for liso-cel [NCT04245839]; ELARA for tisa-cel [NCT03568461]; GO29781 for mosunetuzumab [NCT02500407]; and ROSEWOOD for ZO [NCT03332017]). Based on statistical analyses, visual inspection, and clinical expert input, the PFS and overall survival for all treatments were extrapolated using a log-normal model and an exponential model, respectively. The relative treatment efficacy of mosunetuzumab vs alternative treatment options was estimated from a matching-adjusted indirect treatment comparison analysis. Direct costs in 2024 US dollars (including costs of the drug, wastage, administration, and management of Grade ≥3 severe adverse events and cytokine release syndrome) were evaluated. Over a lifetime horizon, both cost and outcomes were discounted at 3% annually. The cost-effectiveness analysis outputs were measured by dividing the incremental cost by the incremental life year (LY; $ per LY); dividing the incremental cost by the incremental quality adjusted life year (QALY; $ per QALY); and subtracting the incremental cost from the product of incremental QALY and willingness to pay (WTP) threshold of $150,000 per QALY (net monetary benefit [NMB]).

Results: Compared with alternative treatment options, over a lifetime horizon, mosunetuzumab was projected to have a mean total cost of care that was −$795,092 vs ZO; −$321,023 vs axi-cel; −$305,014 vs liso-cel; −$288,633 vs tisa-cel; and −$118,509 vs tazemetostat. In addition, mosunetuzumab was projected to have a mean LY and QALY, respectively, of +9.71 and +7.72 vs tazemetostat; +3.17 and +2.18 vs axi-cel; +5.63 and +4.45 vs ZO; and +0.97 and +0.57 vs tisa-cel. In contrast, liso-cel was projected to have a +0.82 LY and +0.93 QALY vs mosunetuzumab. With the lower cost of care and incremental LY/QALY gains, mosunetuzumab was dominant vs tisa-cel (−$297,009 per LY; −$506,352 per QALY), ZO (−$141,268 per LY; −$178,775 per QALY), axi-cel (−$101,351 per LY; −$147,351 per QALY), and tazemetostat (−$12,199 per LY; −$15,361 per QALY). With the higher cost of care and better outcomes, at a WTP of $150,000 per QALY, liso-cel was not cost-effective vs mosunetuzumab at +$372,165 per LY and +$327,699 per QALY. At a WTP of $150,000 per QALY, the NMB of mosunetuzumab vs alternative treatments was greater than zero, demonstrating mosunetuzumab as cost-effective vs ZO ($1,462,206), tazemetostat ($1,275,779), axi-cel ($647,817), tisa-cel ($374,136), and liso-cel ($165,398).

Conclusions: This study found that mosunetuzumab is a cost-effective treatment vs alternative novel treatment options, for adult patients with 3L+ R/R FL. These findings provide additional economic evidence which has the potential to further inform payers, providers, and patients on how best to value the broadening therapeutic armamentarium in indolent R/R FL. Sensitivity analyses are ongoing to evaluate the robustness of base-case findings. Further analyses are also ongoing and will be presented for the cost-effectiveness of mosunetuzumab vs epcoritamab, which was recently approved for 3L+ R/R FL.

Matasar:Genmab: Membership on an entity's Board of Directors or advisory committees; Genentech: Consultancy, Honoraria, Research Funding; Takeda: Honoraria; IMV Therapeutics: Honoraria; Pfizer: Honoraria; AstraZeneca: Honoraria; Pharmacyclics: Consultancy, Honoraria, Research Funding; Allogene: Membership on an entity's Board of Directors or advisory committees; Merck: Current equity holder in publicly-traded company; Regeneron Pharmaceuticals, Inc.: Honoraria; GM Biosciences: Consultancy, Research Funding; BMS/Celgene: Honoraria; Kite: Honoraria; Epizyme: Honoraria; Immunovaccine Technologies: Research Funding; ADC Therapeutics: Honoraria; Roche: Consultancy, Honoraria, Research Funding; Johnson & Johnson: Consultancy, Honoraria, Research Funding; Bayer: Consultancy, Honoraria, Research Funding; Seattle Genetics: Consultancy, Honoraria, Research Funding. Rosettie:Genentech, Inc.: Current Employment; IQVIA, Inc.: Ended employment in the past 24 months; F. Hoffmann-La Roche Ltd: Current equity holder in publicly-traded company. Mecke:F. Hoffmann-La Roche Ltd: Current Employment; F. Hoffmann-La Roche Ltd: Current equity holder in publicly-traded company. Di Maio:F. Hoffmann-La Roche Ltd: Current Employment; F. Hoffmann-La Roche Ltd: Current equity holder in publicly-traded company; F. Hoffmann-La Roche Ltd: Other. Lin:Genentech, Inc./F. Hoffmann-La Roche Ltd: Current Employment; F. Hoffmann-La Roche Ltd: Current equity holder in publicly-traded company. Wu:F. Hoffmann-La Roche Ltd: Current equity holder in publicly-traded company; Genentech, Inc.: Current Employment. Ma:F. Hoffmann-La Roche Ltd: Current equity holder in publicly-traded company; Genentech, Inc.: Current Employment.