Abstract
BACKGROUND: Relapsed or refractory (R/R) disease following frontline treatment with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) represents a significant clinical challenge in the management of diffuse large B-cell lymphoma (DLBCL). OBJECTIVES: To address unmet medical needs, comprehensive clinical data on R/R DLBCL in real-world settings are warranted. DESIGN: A retrospective observational study including patients from a tertiary medical center and a national population-based cohort. METHODS: We conducted a retrospective cohort study of R/R DLBCL, derived from 665 consecutive patients treated with R-CHOP. Furthermore, a population-based cohort from Taiwan's National Health Insurance Research Database was established for external validation. Clinical data were comprehensively analyzed using Cox proportional hazards regression to identify independent predictors of overall survival (OS) and progression-free survival (PFS). RESULTS: A total of 231 patients were identified from the retrospective cohort. Among them, 88 (38.1%) were found to be primarily refractory to R-CHOP, while 143 (61.9%) experienced recurrent disease. When stratified by time to progression (TTP) after R-CHOP, the 2-year OS rate ranged from 35.4% in patients with TTP <12 months to 74.4% in those with TTP ⩾24 months. Patients with TTP <12 months also demonstrated lower response rates to second-line treatments and were less likely to proceed to stem cell transplantation. In multivariate analysis, TTP was identified as an independent prognostic factor for OS and PFS. The prognostic significance of TTP was further validated in an external, population-based cohort of 723 patients with R/R DLBCL. CONCLUSION: This real-world study provides valuable insights into R/R DLBCL outside of clinical trial settings, revealing that TTP after frontline R-CHOP is an easy-to-use and robust prognostic predictor. Patients with a TTP of less than 12 months exhibited a particularly poor prognosis under conventional treatment, highlighting the urgent need to consider novel therapeutic approaches for this high-risk population.