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Purpose: Etoposide to standard R‐CHOP is used for high‐risk diffuse large B‐cell lymphoma (DLBCL) in some countries. Due to the lack of randomized trials, a real‐world data study using matching methods was used to test the potential effectiveness of R‐CHOEP over R‐CHOP. Patients and Methods: This study included patients from the Danish Lymphoma Register diagnosed between 2006 and 2020 at the age of 18–60 years with de novo DLBCL and age‐adjusted IPI ≥2. R‐CHOEP treated patients were matched 1:1 without replacement to R‐CHOP treated patients using a hybrid exact and genetic matching technique. Primary endpoints were progression‐free survival (PFS) and overall survival (OS). Results: In total, 396 patients were included; 213 received R‐CHOEP and 183 received R‐CHOP. Unadjusted 5‐year PFS and OS for R‐CHOEP were 69% (95% Confidence intervals [CI]; 63%–76%) and 79% (CI;73%–85%) versus 62% (CI;55%–70%) and 76% (CI;69%–82%) for R‐CHOP (log‐rank test, PFS p =.25 and OS p =.31). A total of 127 patients treated with R‐CHOEP were matched to 127 patients treated with R‐CHOP. Matching‐adjusted 5‐year PFS and OS were 65% (CI; 57%–74%) and 79% (CI; 72%–84%) for R‐CHOEP versus 63% (CI; 55%–73%) and 79% (CI;72%–87%) for R‐CHOP (log‐rank test, PFS p =.90 and OS p =.63). Conclusion: The present study did not confirm superiority of R‐CHOEP over R‐CHOP for young patients with high‐risk DLBCL. [ABSTRACT FROM AUTHOR]

ABSTRACT Objectives Methods Results Conclusions Accurate prevalence estimates of diffuse large B‐cell lymphoma (DLBCL) are important for numerous purposes including orphan drug designation. A key criterion for orphan drug designation is a disease prevalence of less than 5/10,000 persons. The objective is to apply and compare different methods of prevalence assessment.In the present nationwide Danish cohort study, the prevalence of DLBCL was assessed using different methodologies, including register‐based and formula‐based approaches.The prevalence calculations were based on 9,492 patients diagnosed with DLBCL since year 2000. Incidence increased and survival improved in the period, resulting in higher prevalence of DLBCL. In year 2023, the 2‐,3‐,5‐,10‐, and 20‐year prevalences were 1.53, 2.19, 3.45, 6.08, and 8.80 per 10,000 adults using the register‐based approach. The formula‐based approach was generally accurate when using restricted mean survival. However, when using median survival, the total prevalence was estimated at 8.1 per 10,000 adults. Furthermore, when extrapolating the median survival from the 5‐year survival under constant hazard assumption as done in some orphan drug designation reports, the prevalence was estimated at 6.6 per 10,000 adults.In conclusion, the estimated DLBCL prevalences are sensitive to the applied method. DLBCL would disqualify from orphan drug designation in some of the mentioned scenarios. [ABSTRACT FROM AUTHOR]

ABSTRACT Introduction Methods Results Conclusion Diffuse large B‐cell lymphoma (DLBCL) exhibits striking clinical and biological heterogeneity. Recent studies have identified new subgroups within germinal center B‐cell like (GCB) DLBCL, associated with inferior prognosis, irrespective of MYC and BCL2 translocations. We explored the existence of such a DLBCL high‐risk subgroup, based on multilevel aberrations, especially focusing on MYC and BCL2.Tissue samples from 111 DLBCL patients were sequenced with a 90‐gene lymphoma panel, followed by integrative analyses combining sequencing data, immunohistochemistry, fluorescent in situ hybridization, and clinical data.We identified a high‐risk subgroup in DLBCL defined by: dual immunohistochemical MYC and BCL2 expression (DEL), concurrent MYC and BCL2 translocations (DHL‐BCL2), mutations in MYC, CXCR4, or both, and/or BCL2 amplification. The high‐risk subgroup constituted 41% of the cohort and included DHL‐BCL2, DEL, a GCB subgroup likely representing the recently described GCB subgroups, and a subset of non‐GCB patients. In multivariate analysis, high‐risk features provided independent predictive value from age and IPI. The 5‐year overall survival was 36% in high‐risk patients, compared to 76% in non‐high‐risk patients.We identified a distinct high‐risk DLBCL subgroup, characterized by MYC and BCL2 aberrations, beyond conventional DHL‐BCL2 and DEL, and irrespective of cell‐of‐origin, thereby expanding the poor‐prognosis group. [ABSTRACT FROM AUTHOR]