Introduction: Few quality of life (QoL) data are available for diffuse large B-cell lymphoma (DLBCL) patients during the first year of diagnosis. Due to the disease and treatment, patients can adapt to their condition and then change their criteria to assess QoL over time, resulting in a response shift (RS) effect. This study aims to provide QoL level for DLBCL patients at diagnosis and after 1 year, and to assess the occurrence of a RS effect. Methods: Data from DLBCL patients prospectively included in the French multicentric cohort REALYSA were used. QoL was collected at diagnosis and at 1 year using the EORTC QLQ-C30 and QLQ-NHL-HG29 (non-Hodgkin high-grade lymphoma) questionnaires. The recently validated QLQ-NHL-HG29 specific questionnaire assesses 5 symptomatic dimensions: symptom burden (SB), neuropathy (NP), physical condition/fatigue (PC), emotional impact (EI), worries/fears about health and functioning (WF). A score is generated per dimension on a 0 to 100 scale. Analyses were done on patients who received standard first-line immunochemotherapy regimen, with QoL questionnaire at diagnosis and at 1 year, and without relapse before 1 year questionnaire completion to avoid bias related to second line therapy. Scores were reported according to age, gender, performance status (PS) and disease stage. We examined the prevalence of clinically important problems/symptoms on QLQ-C30 scales at patient level using validated thresholds (Giesinger et al. J Clin Epidemiol. 2020). The potential occurrence of a RS effect was explored using the Oort procedure. Results: Between Nov 2018 and Dec 2021, 3116 patients were enrolled in REALYSA including 1198 DLBCL. Among 964 patients without relapse at 1 year, 523 had completed questionnaires at baseline and 1 year. For Global QoL, 57% of patients presented clinically important problems at baseline and 42% at 1 year. Regarding the QLQ-NHL-HG29, the mean PC score was 32 (SD 25) [PS 0–1 vs. 2: 29 (SD 24) vs. 47 (SD 25)] at baseline and 23 (SD 21) [PS 0–1 vs. 2: 22 (SD 20) vs. 27 (SD 22)] at 1 year; the mean NP score was 12 (SD 20) [PS 0–1 vs. 2: 11 (SD 19) vs. 16 (SD 26)] at baseline and 23 (SD 28) [PS 0–1 vs. 2: 23 (SD 27) vs. 24 (SD 29)] at 1 year. Among the QLQ-NHL-HG29, a RS effect was observed for NP, PC and WF. The highest effect was observed for NP (Figure 1), suggesting that there is no increase in NP level at 1 year compared to baseline (mean change of -1 points (SD 1)). If no RS effect was considered, it would have been concluded that the NP level had increased at 1 year compared to diagnosis (mean change of 12 points (SD 11)). The research was funded by: Institut National du Cancer (INCa, N°2021-130) Keyword: Aggressive B-cell non-Hodgkin lymphoma No conflicts of interests pertinent to the abstract.