Age and HIV status as survival predictors in HHV8-positive diffuse large B-cell lymphoma: The largest population-based analysis to date.

7084 Background: HHV8-positive Diffuse Large B Cell Lymphoma (HHV8+ DLBCL) is a rare and aggressive subtype of Non-Hodgkin Lymphoma that is frequently associated with HHV8-positive Multicentric Castleman Disease (MCD). Due to its rarity, population-based studies have been limited to small cohorts or have focused primarily on demographic features without survival analysis. This study explores demographic features, treatment pattern and prognostic factors affecting survival in patients diagnosed with (HHV8+ DLBCL) in the United States. Methods: Following IRB approval, we analyzed the largest cohort of HHV8+ DLBCL to date (n=262) using the National Cancer Database (NCDB) (2010-2023). Patients with histologically confirmed HHV8+ DLBCL (ICD-O-3 9738/3) were included. Univariable Cox regression identified factors associated with survival; significant variables were included in multivariable cox regression with backward elimination (p<0.05). Data was analyzed using SAS version 9.4. Results: Among 262 patients with HHV8+ DLBCL, (mean age 52.6 years), 65.6% were <60 years, 76.7% were male, and 66.0% were white. Primary site was predominantly nodal (78.6%), with extranodal involvement in 21.4%. 19.2% were HIV-positive, and 63.3% had no comorbidities (Charlson-Deyo score 0). The majority received systemic therapy (84.6%). Among treated patients, 62.2% received chemotherapy and 43.1% received immunotherapy. Median overall survival was 133 months, with 1-, 3- and 5-year survival rates of 68.2%, 63.1%, and 59.9%, respectively. On multivariable Cox regression analysis, age ≥60 years (HR 2.20, p=0.0004), higher Charlson-Deyo score (HR 1.67, p=0.0090), HIV-positive status (HR 2.56, p=0.0026), and absence of systemic treatment (HR 2.16, p=0.0016) was independently associated with worse overall survival. Conclusions: In conclusion, HHV8+ DLBCL is a rare and aggressive lymphoma with poor long-term survival, frequently associated with multicentric Castleman disease, mainly affecting males with nodal involvement. Age ≥60 years, higher Charlson-Deyo score, HIV-positive status, and lack of systemic treatment independently predicted worse survival. Our study provides the largest cohort analysis of HHV8+ DLBCL to date. Nevertheless, further prospective studies with larger sample sizes are necessary to gain deeper insight into the pathogenesis and optimize treatment of this rare lymphoma. Multivariable Cox regression for overall survival in patients with HHV8+ DLBCL. Factor HR (95%CI) p-value Age Age <60 (ref) Age ≥60 12.20(1.42-3.40) 0.0004 Charlson Deyo ScoreNo morbidities (ref)≥1 Morbidities 11.67(1.14-2.44) 0.0090 Systemic Treatment Status No TreatmentReceipt of Treatment (ref) 2.16(1.34-3.48)1 0.0016 HIV Negative (ref) Positive Unknown 12.56(1.39-4.71)0.96(0.59-1.56) 0.00260.8601