Background:

Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of non-Hodgkin lymphoma both globally and in Saudi Arabia. It is typically treated with chemo-immunotherapy regimens with curative intent at the time of initial diagnosis. Treatment-related mortality ranges from 2% to 8%, and the disease is associated with significant acute and long-term toxicities. However, regional data on clinical characteristics and outcomes remain limited.

Methods:

This retrospective cohort study included 516 patients aged ≥14 years who were diagnosed with DLBCL between January 2016 and December 2023 at two large hospitals in Saudi Arabia. Data on demographics, disease features, treatment regimens, and outcomes were collected. All statistical analyses were performed using Python (v3.9) with standard open-source libraries. Survival outcomes were assessed using Kaplan–Meier estimates and Cox proportional hazards regression models

Results:

The median age at diagnosis was 60.5 years, with 53% of patients under the age of 65 (n = 241). The majority of patients (77%) presented with advanced-stage disease. Among biomarkers, BCL6 was most commonly reported, followed by BCL2, CD10, and MYC. The R-CHOP regimen was the most frequently used first-line treatment, especially among younger patients (95% vs. 62% in older patients). CAR T-cell therapy was administered as second-line treatment in 7% of younger patients and 6% of those aged 65 years or older. Complete remission was achieved in 74% of patients under 65 and 66% of those 65 and older (p = 0.09). Relapsed or refractory disease occurred more frequently in older patients (40% vs. 27%, p = 0.0019). Two-year progression-free survival was 78% in younger patients and 64% in older patients (p = 0.004), while two-year overall survival was 87% and 76%, respectively (p = 0.001).

Multivariable Cox regression analysis identified the following as independent predictors of worse overall survival: increasing age (HR 1.025; 95% CI 1.011–1.040; p = 0.0003), higher ECOG performance status (HR 1.595; 95% CI 1.311–1.940; p < 0.0001), presence of comorbidities (HR 2.278; 95% CI 1.057–4.910; p = 0.036), MYC expression (HR 2.233; 95% CI 1.342–3.717; p = 0.002), and kidney involvement (HR 2.432; 95% CI 1.225–4.830; p = 0.010). BCL6 and BCL2 expression were not significantly associated with overall survival.

Conclusion:

This study provides valuable real-world insights into the clinical presentation and outcomes of DLBCL in Saudi Arabia. Overall outcomes are comparable to international data; however, older age, comorbidities, MYC expression, and renal involvement are associated with poorer prognosis. As the field advances toward precision medicine, more detailed molecular profiling and treatment response data are needed. The establishment of a national lymphoma registry is essential to support evidence-based, personalized care and guide future research and treatment strategies.

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2025
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