A United States (US) Cost-Effectiveness Analysis of Axicabtagene Ciloleucel Compared to Odronextamab in Third Line or Later (3L+) Diffuse Large B-Cell Lymphoma
Authors: Locke Frederick , Kievit Bradley , Wade Sally W. , Blisset Rob , Ray Markqayne , Palivela Madhu , Best Timothy , Oluwole Olalekan O. 
Published: December 2024

Introduction
Relapsed/Refractory (R/R) diffuse large B-cell lymphoma (DLBCL) following at least two lines of therapy (2L+) historically carried a poor prognosis. The advent of chimeric antigen receptor T-cell (CAR T) therapy in 2L+ provides patients with a potentially curative treatment. The emergence of bispecific antibodies has also expanded the treatment options in R/R DLBCL. Results of the Phase 2 ELM-2 trial positions odronextamab (odro), a novel bispecific agent, for regulatory approval in 3L+ DLBCL. The current study extends our published discrete event simulation (DES) model which evaluated cost-effectiveness of axicabtagene ciloleucel (axi-cel) versus glofitamab and epcoritamab (Locke et al. Transplant Cell Ther 2024a,b) to now assess the relative cost-effectiveness of axi-cel versus odro in R/R 3L+ DLBCL.
Methods
A DES model was employed to project lifetime health and economic outcomes for patients initiating either axi-cel or odro in the 3L+ setting for DLBCL. Clinical data was leveraged from Phase 2 trials for axi-cel and odro, ZUMA-1 and ELM-2, respectively. The base case analysis incorporated survival data derived from a matching adjusted indirect treatment comparison of axi-cel and odro. A scenario analysis using a naïve head-to-head comparison was also performed. Mixture cure models were utilized to extrapolate survival data for both treatments given long-term survival benefits seen with axi-cel.
Given significant uncertainty for the durability of response for odro, the base case cure fraction was assumed to be 10%, in line with recent analyses for epcoritamab and glofitamab and based on clinical expertise. A scenario analysis was conducted with the cure fraction at 15%, based on the proportion of ELM-2 patients who maintained a complete response for 24 months. Conducted from a US payer perspective, treatment data and costs were sourced from literature and Micromedex, adjusted to 2023 US dollars. As odro does not have a publicly available list price, its cost was benchmarked against epcoritamab, due to similarities in treat-to-progression regimens, and was varied in scenario analyses. Costs and health utilities were discounted at an annual rate of 3.0% consistent with standard US practice.
Results
In the base case, axi-cel resulted in longer survival compared to odro. For instance, progression-free survival (PFS) duration favored axi-cel (5-yr PFS: 39.6% vs 10.7% for axi-cel and odro, respectively). In addition, treatment with axi-cel resulted in 7.46 life years (LYs) compared to 3.27 LYs for odro, resulting in an incremental difference of 4.19 LYs, favoring axi-cel. Longer overall survival based on the discounted quality-adjusted life years (QALYs) were also higher for axi-cel compared to odro (5.85 versus 2.25). Axi-cel patients had total discounted lifetime costs of $603,310 compared to the odro arm's $1,134,778. Axi-cel is therefore a dominant treatment option, meaning it is more efficacious and less costly than odro. These results were very similar when using the naïve survival data and when the odro cure fraction was set to 15%, as conclusions remain unchanged.
To understand the impact of the uncertainty of the odro price prior to launch, we reduced the price by 20-80% of the base case. At 80% and 60% of the base case, axi-cel was the dominant strategy. For the 20% and 40% scenarios, the axi-cel incremental cost effectiveness ratios of $84,711 and $26,626 respectively, would still be considered cost-effective by prevailing US thresholds of $150,000/QALY. In a further scenario analysis, the maximum treatment duration for odro was restricted to 2 years, which resulted in discounted costs in the odro arm of $651,366, which again resulted in axi-cel being a dominant treatment strategy.
Conclusions
Results suggest that axi-cel is highly cost-effective compared to odro in a R/R 3L+ DLBCL setting in the US. The higher lifetime treatment cost with odro suggests a treat-to-progression strategy would result in higher costs over time compared to the upfront costs of axi-cel, while still resulting in inferior long-term clinical outcomes. A strength of the analysis is that both trials underpinning the model were conducted in CAR T naïve patients. A limitation is that the comparison has been undertaken before availability of the odro list price. Future research is needed to confirm these findings when long-term survival and the published price of odro become available.