Retrospective Cohort Analysis of Treatment Patterns, Survival, and Cost-Effectiveness in Relapsed/Refractory Diffuse...

R/R DLBCL is an aggressive malignancy with limited treatment options. Novel immunotherapies have improved outcomes in selected clinical-trial populations, but their effectiveness in real-world settings remains unclear. Their substantial costs also pose challenges for healthcare systems.

This exploratory study evaluated the efficacy and costs of available therapies in a real-world population. Two retrospective analysis approaches were used: First, we compared calendar-based cohorts: A conventional-treatment period (1 January 2018-31 December 2019), which predates EMA approval of Polatuzumab-vedotin, and a modern-treatment period (1 January 2020-31 December 2022). Second, because treatments overlapped across periods, we additionally grouped patients by therapy exposure and compared those receiving any modern therapy at any stage with those treated exclusively with conventional regimens.

Comparing the calendar-based periods provided limited insights, as therapies unavailable in the earlier period could still be used in subsequent treatment lines. In contrast, grouping patients by exposure to modern therapy at any stage showed a clear survival benefit: Median OS was 20 vs. 5 months (95% CI: 1.8-38.2 vs. 3.0-7.0; p = 0.022). This advantage was associated with significantly higher mean costs (€178,513.08 vs. €15,185.08; p < 0.001), resulting in an incremental cost of €10,889 per additional month of survival.

Modern therapies for r/r DLBCL have significantly improved survival rates, but their high costs necessitate careful cost-effectiveness assessments to ensure they are integrated optimally into clinical practice. Additionally, our findings indicate that calendar-based comparisons can be misleading, since novel treatments do not simply "start" and "stop" at approval dates-a crucial methodological insight that is highly generalizable to real-world evidence studies. Grouping patients by actual therapy exposure offers a more accurate evaluation of clinical benefits and economic impact when new treatments become routine. Achieving equitable access to treatment while maintaining healthcare sustainability will require coordinated efforts among clinicians, researchers, and policymakers.