Diffuse large B-cell lymphoma (DLBCL) patients have a median age of 70 years. Yet, empirical knowledge on treatment for older patients is limited as they are frequently excluded from clinical trials. We aimed to construct a simplified frailty score and examine survival and treatment-related mortality (TRM) according to frailty status and treatment intensity in an older, real-world DLBCL population. All patients ≥70 years diagnosed with DLBCL 2006-2016 in south-eastern Norway (n=784) were included retrospectively, and divided into a training (n=522) and validation cohort (n=262). We constructed and validated a frailty score based on geriatric assessment variables, and examined survival and TRM according to frailty status and treatment. The frailty score identified three frailty groups with distinct survival and TRM, independent of established prognostic factors (2-year overall survival (OS) fit 82%, unfit 47%, frail 14%, P<0.001). For fit patients, full-dose R-CHOP (initial dosage>80%) was associated with better survival than attenuated R-CHOP (2-year OS 86% vs 70%, P=0.012), also in adjusted analysis. For unfit and frail patients, full-dose R-CHOP was not superior to attenuated R-CHOP, while an anthracycline-free regimen was associated with poorer survival in adjusted analyses. A simplified frailty score identified unfit and frail patients with higher risk of death and TRM, which can aid treatment intensity decisions in older DLBCL patients. In this study, fit patients benefit from full-dose R-CHOP, while unfit and frail patients have no benefit of full-dose R-CHOP over R-miniCHOP. An online calculator for assessment of the frailty score is available at https://wide.shinyapps.io/app-frailty/.

International prognostic Index (IPI) is the most widely used clinical prediction model for diffuse large B-cell lymphoma (DLBCL) patients treated with rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP), but may be suboptimal in older patients. We aimed to develop and externally validate a clinical prediction model for older, R-CHOP treated DLBCL patients by examining geriatric assessment and lymphoma-related parameters in real-world cohorts. A population-based training set of 365 R-CHOP treated DLBCL patients ≥70 years was identified through the Cancer Registry of Norway. The external test set consisted of a population-based cohort of 193 patients. Data on candidate predictors was retrieved from the Cancer Registry and through review of clinical records. Cox regression models for 2-year overall survival (OS) were used for model selection. Activities of daily living (ADL), Charlson Comorbidity index (CCI), age, sex, albumin, stage, ECOG and LDH were identified as independent predictors and combined into a Geriatric prognostic index (GPI). The GPI demonstrated good discrimination (optimism-corrected C-index 0.752), and identified a low-, intermediate- and high-risk group with significantly different survival (2-year OS 94%, 65%, 25%). At external validation, the continuous and grouped GPI demonstrated good discrimination (C-index 0.727, 0.710) and the GPI groups had significantly different survival (2- year OS 95%, 65%, 44%). Both the continuous and grouped GPI showed better discrimination than IPI, R-IPI and NCCN-IPI (C-index 0.621, 0.583, 0.670) We have developed and externally validated the GPI for older DLBCL patients treated with RCHOP that outperformed IPI, R-IPI and NCCN-IPI. A web-based calculator is available at https://wide.shinyapps.io/GPIcalculator/.

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