Insights into the survival impact of delayed immunochemotherapy in newly diagnosed diffuse large B-cell lymphoma: results from a nationwide registry study

Abstract

BACKGROUND: The prognostic impact of the diagnosis-to-treatment interval (DTI) in diffuse large B-cell lymphoma (DLBCL) remains controversial. We investigated the association between DTI and three-year all-cause mortality in a nationwide cohort. METHODS: We conducted a retrospective population-based cohort study using harmonised German cancer registry data (2020-2023), with vital status follow-up until December 2024. Patients with a first primary DLBCL diagnosis were included. Kaplan-Meier analyses and Cox regression assessed DTI in relation to survival, unadjusted and adjusted for patient, tumor, and structural characteristics. Missing International Prognostic Index (IPI) data formed a separate category, with complete-case and imputation sensitivity analyses. RESULTS: Of 16,443 patients, 10,872 initiated systemic therapy within 56 days (eight weeks) and entered the primary analysis. Median age was 71 years, 44.2% were female, and median follow-up was 1.5 years. Three-year overall survival ranged from ~ 63% to 75% across the five treatment-week groups. Compared with week 1, later initiation was associated with progressively lower hazard of death (week 3: HR 0.72, 95% CI 0.64-0.81; week 4: HR 0.63, 0.55-0.72; weeks 5-8: HR 0.62, 0.54-0.70). Lower-risk IPI predicted better survival (low risk: HR 0.24, 0.17-0.34 vs high risk). Later initiation was predicted by low-risk IPI (+ 7.89 days), older age (+ 0.62 days/SD), and surviving the first year (+ 3.26 days). CONCLUSION: Early treatment in DLBCL is primarily driven by adverse disease characteristics. A residual association between longer DTI and improved survival persisted after IPI adjustment, suggesting DTI may be an independent prognostic factor in less aggressive disease.