A simplified frailty score predicts survival and can aid treatment-intensity decisions in older patients with DLBCL

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/.