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Background and Importance Standard first-line treatment for high risk DLBCL is R-CHOP/COMP or R-Pola-CHP (IPI 3-5). For patients ≥80 years or those classified as frail (by CGA/EPI), guidelines recommend reducing chemotherapy dose by 50% or offering palliative care. Relative Dose Intensity (RDI)–the administered-to-planned dose ratio–is a key metric to balance therapeutic efficacy and toxicity. 1 Aim and Objectives This study retrospectively evaluated the impact of RDI of R-CHOP-like regimens (rituximab, cyclophosphamide, doxorubicin) and clinical variables (IPI, EPI, SGA) on Overall, Progression-Free, and Event-Free Survival (OS, PFS, EFS) in adult, newly diagnosed DLBCL patients (2018–2024). Exclusions: high-dose chemotherapy, Richter’s, Primary Mediastinal, and CNS lymphomas.Material and Methods Chemotherapy doses, extracted from software, were converted to mg/m2/week to calculate RDI.A multivariate Cox regression (CR) was performed (R software, version 4.2.2) for OS, PFS, and EFS, using RDI of key agents and clinical variables (histology, IPI, EPI risk, SGA, age) as covariates.Results The analysis of 182 patients (median age 78, 81 female) showed that higher RDI significantly improved survival.Specifically: Cyclophosphamide RDI favoured OS (HR 0.97,p 0.016).Doxorubicin RDI benefited OS, EFS, and PFS (HR 0.75−0.82, p 0.03−0.075).Conversely, poor prognosis factors worsened outcomes:IPI score negatively impacted OS, EFS, and PFS (HR 1.31−1.57, p 0.018−0.086).non–GCB histology worsened OS (HR 1.8, p 0.092).SGA ‘unfit’ classification significantly reduced EFS and PFS (HR 2.87−3.02, p 0.04−0.052).EPI was not statistically significant.These findings strongly support maintaining dose intensity in fit elderly patients.Conclusion and Relevance This study confirmed that RDI is a critical determinant of outcome. Higher RDI of doxorubicin (HR 0.75−0.82) and cyclophosphamide (HR 0.97) was significantly associated with improved OS, EFS, and PFS. This supports maintaining maximal feasible dose when patient fitness allows.In sharp contrast, established prognostic factors showed a strong negative impact.A high IPI score significantly worsened all survival endpoints (HR 1.31−1.57), and non-GCB histology negatively affected OS (HR 1.8).These factors underscore the dual challenge in DLBCL: maximising therapeutic delivery while mitigating inherent disease and patient risks.Crucially, frailty, as defined by an ‘unfit’ SGA classification, was highly detrimental to EFS/PFS (HR 2.87−3.02).These data underscore the need for careful geriatric assessment and individualised dosing to maximise RDI safely in fit elderly patients.References and/or Acknowledgements 1. Kwak LW, et al. J Clin Oncol. 1990 Jun;8(6):963–77.Conflict of Interest No conflict of interest