Cost-Effectiveness of Epcoritamab Versus Glofitamab in Relapsed or Refractory Large B-Cell Lymphoma after at Least Two Lines of Therapy in the United States

Background: Epcoritamab is a first-in-class subcutaneously (SC) administered CD3xCD20 bispecific antibody (bsAb) for the treatment of adult patients with relapsed or refractory diffuse large B-cell lymphoma (R/R DLBCL). In the single-arm, phase 1/2, EPCORE NHL-1 trial (NCT03625037), epcoritamab demonstrated deep and durable responses with manageable safety in patients with R/R LBCL, and a median overall survival (OS) of 18.5 months. A second CD3xCD20 bsAb was subsequently approved for third-line R/R DLBCL or LBCL with intravenous (IV) administration, glofitamab, with a median OS of 11.5 months. A cost-effectiveness analysis is needed due to insufficient available evidence regarding the relative costs and survival outcomes of epcoritamab vs glofitamab.

Aims: This study evaluated the cost-effectiveness of epcoritamab vs glofitamab in patients with R/R LBCL from a US healthcare sector perspective.

Methods: A partitioned survival model with 3 health states (progression free [PF], progressive disease [PD], and death) based on OS and progression-free survival (PFS) was developed. OS, PFS, time to treatment discontinuation (TTD), health utilities, and adverse events of epcoritamab were informed by patient-level data from the EPCORE NHL-1 trial (data cutoff April 2023, N=157) whereas OS and PFS aggregate data of glofitamab was utilized from the NP30179 trial (Dickinson et al. 2022, N=155). In the model base case, parametric survival models were chosen for extrapolating OS and PFS as well as TTD for epcoritamab based on statistical fit and plausibility on long-term clinical estimates. An unanchored matching-adjusted indirect comparison (MAIC) analysis was conducted to assess the relative efficacy of epcoritamab vs glofitamab. The analysis was conducted by adjusting for imbalances in baseline characteristics. Piece-wise hazard ratios (HRs) for epcoritamab vs glofitamab were calculated for OS due to violation of the proportional hazards with the first HR calculated before 6 months (HR: 1.18, 95% CI: 0.77-1.81) and the second HR calculated after 6 months. This demonstrated a statistically significant OS benefit for epcoritamab vs glofitamab (HR: 0.57, 95% CI: 0.34-0.94). PFS HR for epcoritamab vs glofitamab was 1.04 (95% CI: 0.77-1.39). Health utilities for PF and PD were based on EQ-5D-3L data collected from EPCORE NHL-1 and a published US value set. Drug acquisition and administration costs and other resource use (eg, monitoring, subsequent therapy, labs, etc) and cost data were based on package inserts, US standard sources, and literature. The primary outcome was incremental cost-effectiveness ratio (ICER). Based on expert feedback, it was assumed that no additional drug costs for epcoritamab would be incurred after 2 years in the base case. All outcomes and costs were discounted by 3% annually. Probabilistic, one-way sensitivity analyses and a range of scenario analyses were conducted to assess the robustness of the results.

Results: Over a lifetime horizon, epcoritamab was estimated to result in a mean gain of 2.33 life years (LYs) and 1.32 quality-adjusted LYs (QALYs) vs glofitamab, with a cost difference of $116,272, leading to an ICER of $88,189 per QALY. Sensitivity analyses using a 3-year treatment duration and no limitation on treatment duration (for epcoritamab) led to ICERs of $103,518 and $117,801 respectively. Thus, epcoritamab was cost-effective in comparison to glofitamab at a standard US willingness-to-pay threshold of $150,000 per QALY in the base case as well as in sensitivity analyses. Additionally, the average cost per LY was $56,671 less for epcoritamab vs glofitamab.

Conclusion: SC epcoritamab provides meaningful LY and QALY gains vs IV glofitamab. This analysis suggests that epcoritamab is likely to be a more cost-effective option for managing R/R LBCL from a US healthcare sector perspective.

Fox:Gilead/Kite: Consultancy; AbbVie: Consultancy, Other: Trial Steering Committee, Research Funding; Takeda: Consultancy; BeiGene: Research Funding; Lilly: Consultancy; Incyte: Consultancy; Janssen: Consultancy; Genmab: Consultancy, Other: Trial Steering Committee, Research Funding; SOBI: Consultancy; Ono: Consultancy; MorphoSys: Consultancy; BMS: Consultancy; Atarabio: Consultancy; AstraZeneca: Consultancy; SERB: Consultancy; Roche: Consultancy. Riedell:Fate Therapeutics: Research Funding; AbbVie: Consultancy, Membership on an entity's Board of Directors or advisory committees; ADC Therapeutics: Consultancy, Membership on an entity's Board of Directors or advisory committees; Genentech/Roche: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Sana Biotechnology: Consultancy, Membership on an entity's Board of Directors or advisory committees; Genmab: Consultancy, Membership on an entity's Board of Directors or advisory committees; Adaptive Biotechnologies: Honoraria; BeiGene: Consultancy, Membership on an entity's Board of Directors or advisory committees; BMS: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Kite/Gilead: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Cellectis: Research Funding; Tessa Therapeutics: Research Funding; Cargo Therapeutics: Research Funding; Calibr: Research Funding; CRISPR Therapeutics: Research Funding; Xencor: Research Funding; Pharmacyclics: Consultancy, Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees; CVS Caremark: Consultancy, Membership on an entity's Board of Directors or advisory committees; Intellia Therapeutics: Consultancy, Membership on an entity's Board of Directors or advisory committees; Nektar Therapeutics: Consultancy, Membership on an entity's Board of Directors or advisory committees. Qu:Lumanity: Current Employment. Jun:Genmab: Current Employment, Current equity holder in publicly-traded company, Other: stockholder. Chhibber:Genmab: Current Employment, Current equity holder in publicly-traded company, Other: stockholder. Mutebi:Genmab: Current Employment, Current equity holder in publicly-traded company, Other: stockholder. Li:AbbVie: Current Employment, Other: stockholder of AbbVie. Meng:Lumanity: Current Employment. Wang:AbbVie: Current Employment, Current equity holder in publicly-traded company, Other: stockholder of AbbVie. Alshreef:AbbVie: Current Employment, Current equity holder in publicly-traded company, Other: stockholder.