Background: Diffuse large B-cell lymphoma (DLBCL) is the most frequently diagnosed lymphoma and often cured in first- or second-line treatment. However, it is estimated that ~20-30% of the patients (pts) will continue to relapse and require multiple lines of treatment. These pts may spend considerable time receiving therapy, undergoing monitoring for progression and complications, and managing adverse events (AEs) contributing to “time toxicity” that can reduce their quality of life. To assess the impact of time toxicity in relapsed or refractory (R/R) third-line or later (3L+) DLBCL, a cost consequence model was developed to compare clinical outcomes, time toxicity, and costs for axicabtagene ciloleucel (axi-cel), a chimeric antigen receptor T-cell therapy given as a one-time infusion, and two bispecific antibodies (BsAbs): epcoritamab (epcor; delivered in 28-day cycles until disease progression) and glofitamab (glofit; delivered over twelve 21-day cycles).

Methods: A Microsoft Excel-based model was developed using a spline-based, mixture-cure partitioned survival structure. Model inputs were derived from published literature, Centers for Medicare & Medicaid Services Fee Schedules, RED BOOK®, and internal Kite Pharma data. Overall survival (OS) and progression-free survival (PFS) data were sourced from matching-adjusted indirect comparisons (MAIC) and extrapolated assuming various parametric distributions and cure fractions of 31% (axi-cel) and 10% (BsAbs), per ZUMA-1 data and prior DLBCL models. Time toxicity was defined as total pt time spent receiving medical care, including all instances of healthcare resource utilization (HCRU)—inpatient stays, outpatient visits, laboratory tests, AE-related hospitalizations—and associated travel time. Median PFS and OS, annualized time toxicity days, direct medical (primary and subsequent therapy, AE, health state, and terminal care) and non-medical (travel) costs, indirect costs (productivity losses), total costs, and cost per PFS/OS were estimated over a lifetime horizon post-treatment initiation. The model also calculated travel-related burden: distance traveled, travel time, driving costs, and productivity loss associated with travel time. One-way sensitivity analyses (OWSAs) assessed model robustness. Costs were adjusted to 2025 US dollars and discounted 3% per standard practice.

Results: Over a lifetime horizon, axi-cel demonstrated superior clinical outcomes versus epcor and glofit. Assuming MAIC and mixture-cure methods, median PFS and OS were longer for pts with axi-cel versus epcor (PFS: 1.4 vs 0.6 years; OS: 3.7 vs 2.5 years) and glofit (PFS: 1.2 vs 0.7 years; OS: 2.7 vs 1.7 years). Axi-cel was associated with fewer per-pt annualized time toxicity days compared to epcor and glofit (-4.0 and -1.0 days, respectively), driven by reductions in primary therapy outpatient administration visits, laboratory tests, and monitoring events (-3.5, -0.5, and -0.4 [vs epcor]; -1.4, -0.4, and -0.3 [vs glofit], respectively). Axi-cel incurred higher per-pt total costs relative to epcor and glofit ($892,266 vs $850,802; $880,847 vs $644,295). Despite axi-cel's higher primary therapy costs (difference: $151,888 [vs epcor]; $325,259 [vs glofit]), reductions were observed in subsequent therapy, AE, and terminal care costs (difference: -$111,239 [vs epcor]; -$95,269 [vs glofit]). On an annualized basis, axi-cel had a lower cost per PFS- and OS-year vs both BsAbs (-$118,625 and -$20,335 [vs epcor]; -$27,750 and -$6,666 [vs glofit]). Travel burden was reduced with axi-cel relative to both BsAbs, with pts traveling fewer miles (-1,122 [vs epcor]; -109 [vs glofit]) and spending fewer hours in transit (-37.4 [vs epcor]; -3.6 [vs glofit]), resulting in lower driving and travel-related productivity loss costs. OWSAs identified the OS and PFS hazard ratios of the BsAbs relative to axi-cel, BsAbs cure fraction, and BsAbs discontinuation as key drivers of time toxicity.Conclusion: For pts with R/R 3L+ DLBCL, axi-cel offers superior efficacy and reduces time toxicity and travel burden over a lifetime horizon, despite incurring higher per-pt costs compared to BsAbs. Axi-cel, a one-time therapy, may enhance the overall pt experience, by extending PFS, reducing HCRU and time toxicity, lowering pt burden, and improving quality of life.

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2025
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