Cost Consequence and Time Toxicity Model for the Treatment of Third-Line or Later (3L+) Follicular Lymphoma (FL) Using Advanced Therapies: A Comparison of Lisocabtagene Maraleucel (liso-cel) with Mosunetuzumab

Background: FL is an incurable but manageable form of NHL that involves long-term management, frequent relapses, and multiple lines of therapy, which contribute to a serious burden on patients. Liso-cel, an autologous, CD19-directed, 4-1BB CAR T cell product, and mosunetuzumab, a CD20×CD3 bispecific antibody, are treatments for adults with R/R FL who have had ≥ 2 previous lines of systemic therapy. Liso-cel involves a 1-time infusion; mosunetuzumab typically involves 8–17 infusions but is more readily available than liso-cel. Economic, clinical, and quality of life outcomes are commonly analyzed in published literature, but the amount of time spent by a patient seeking care, or time toxicity, is not considered. To evaluate key differences between liso-cel and mosunetuzumab, a cost consequence model was developed to calculate total costs, outcomes, and time toxicity for patients treated with these advanced therapies for 3L+ FL.

Methods: A health economic model was created with Microsoft Excel using parametric techniques to estimate patient survival and PFS. Time toxicity, clinical, and economic outcomes were estimated over a range of time horizons (1–5 years, 10 years, and lifetime) while using 5 years as the base case. Time toxicity was defined as time spent receiving medical care, including outpatient, inpatient, and emergency care, and was measured by accounting for every instance of health care resource utilization (HCRU) by a patient, including outpatient visits, laboratory tests, and others (Gupta A, et al. J Clin Oncol 2022). Patients treated with liso-cel incurred pretreatment costs, including leukapheresis, bridging therapy, and lymphodepletion. Liso-cel involved 1 administration, while mosunetuzumab was given for 8 infusions, based on the observed median number of cycles from the clinical trial. Postadministration monitoring, long-term monitoring, progression-related costs, and AE rates (including cytokine release syndrome, neurological events, serious infections, and cytopenias) were included in this analysis. Indirect costs included travel costs for outpatient visits or hospitalizations, and lost wages. Productivity loss was also included, which accounted for 8 hours of work or nonwork-related productive time loss when receiving care. Lost wages were calculated by applying the employment rate for people ≥ 60 years of age to the total hours lost and applying the average wage/hour. Data sources for the model included published literature (Nastoupil LJ, et al. Blood 2023; Budde LE, et al. Lancet Oncol 2022), publicly available resources, and internal Bristol Myers Squibb data. Unit costs were adjusted to 2024 United States dollars and viewed from a health care system perspective.

Results: Over a 5-year period, patients treated with liso-cel had a higher modeled median PFS of 51 months compared with 18 months for mosunetuzumab, providing an additional 0.87 progression-free life-years. This resulted in a cost per median PFS month of $11,650 for liso-cel and $18,180 for mosunetuzumab. However, patients treated with liso-cel incurred an additional $265,226 compared with mosunetuzumab, primarily due to high acquisition cost of liso-cel. The time toxicity for patients treated with mosunetuzumab was 44 days longer than patients treated with liso-cel, owing to more disease progression and additional infusion visits. As the time horizon increased, this differential widened due to worse disease progression. The increased HCRU translated to 1148 additional hours in productivity loss, $3126 in lost wages, 246 more miles traveled, and an additional $1323 in transportation costs for patients treated with mosunetuzumab. Deterministic sensitivity analysis showed that total cost difference was most affected by the total acquisition cost (and therefore the number of cycles administered), the proportion of patients receiving liso-cel after leukapheresis, and subsequent therapy costs for both therapies.

Conclusions: The model demonstrated that while liso-cel has a higher total cost for patients with 3L+ FL, it offers clinical and nonclinical benefits compared with mosunetuzumab. The increase in PFS with liso-cel versus mosunetuzumab translates to less downstream HCRU. Further, as liso-cel only requires a single administration, it provides reduced time toxicity, travel distance, and productivity loss, which improve the quality of life of patients and their caregivers.