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

Introduction: Epcoritamab (SC) is a CD3xCD20 bispecific antibody developed using the DuoBody^® platform for the treatment of adult patients with relapsed or refractory diffuse large B-cell lymphoma (r/r DLBCL), not otherwise specified, including DLBCL arising from indolent lymphoma, and high-grade B-cell lymphoma after two or more lines of systemic therapy in the US. In the single-arm, phase I/II, EPCORE-NHL-1trial (NCT03625037), epcoritamab (SC) demonstrated deep and durable responses and manageable safety in patients with r/r DLBCL. This study evaluated the cost-effectiveness of epcoritamab versus gemcitabine-oxaliplatin plus rituximab (R-GemOx) and the chimeric antigen receptor T-cell (CAR T) therapy axicabtagene ciloleucel (axi-cel) for adult patients with r/r DLBCL and no prior CAR T therapy from a US health system perspective.

Methods: A partitioned survival model with three health states (progression-free [PF], progressive disease [PD], and death) based on overall survival (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 the corresponding patient level data from EPCORE-NHL-1 (data cut-off: June 2022). In the model base case, parametric survival models were chosen to extrapolating OS and PFS as well as TTD for epcoritamab based on statistical fit and plausibility on long-term clinical estimates. Two separate unanchored matching-adjusted indirect comparison (MAIC) analyses were conducted to assess the relative effectiveness of epcoritamab versus R-GemOx or axi-cel. In the first analysis, epcoritamab patients were matched with SCHOLAR-1 patients for comparison with R-GemOx (OS hazard ratio [HR] 0.288, 95% confidence interval [CI] 0.162-0.511). SCHOLAR-1 was chosen because it was the largest patient-level pooled retrospective analysis for r/r DLBCL, pooling outcomes from 2 large RCTs and 2 academic databases. In the second analysis, epcoritamab patients were matched with ZUMA-1 for comparison with axi-cel (OS HR 0.695, 95% CI 0.351-1.376). ZUMA-1 was chosen because it had long-term efficacy data reported. Patients in PF health states were assumed cured beyond two years when the risk of mortality became comparable to the general population (standard mortality ratio of 1.41 to be more conservative and consistent with prior NICE technology assessment submissions) and no further drug costs of epcoritamab were incurred. Health utilities for PF (0.825) and PD (0.779) health states were estimated using linear mixed-effects models 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 and cost data were based on package inserts, US standard sources, and literature. The model reported costs, life years (LYs), quality-adjusted life years (QALYs), incremental cost-effectiveness ratio (ICER) and incremental net monetary benefit (INMB) at a willingness-to-pay (WTP) threshold of $100,000 to $150,000 per QALY. All outcomes and costs were discounted by 3% annually. Probabilistic and one-way sensitivity 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 4.26 LYs and 2.70 QALYs with additional costs of $285,093 versus R-GemOx, leading to an ICER of $105,502 per QALY; epcoritamab was estimated to dominate axi-cel by gaining 2.12 LYs and 1.29 QALYs while saving $180,518 costs. When drug acquisition costs (e.g. axi-cel one-time treatment cost) are not included in the sensitivity analyses, model results were most sensitive to OS HR, age, and HR to adjust background mortality for the cured population for comparison with R-GemOx; and to OS HR, PFS HR, and age for comparison with axi-cel. Epcoritamab was highly cost-effective compared to R-GemOx and aix-cel when WTP threshold was $150,000 per QALY or higher. This study had several limitations including unanchored MAIC approach used and the relatively short follow-up time and small (effective) sample size of the survival data of epcoritamab.

Conclusion: Epcoritamab provides substantial LYs and QALYs gains versus R-GemOx and axi-cel and can be considered cost-effective compared to R-GemOx and axi-cel for the treatment of r/r DLBCL in the US.