Abstract
Background Human herpesvirus 8–positive diffuse large B-cell lymphoma (HHV8+ DLBCL) is a rare and aggressive subtype of DLBCL, accounting for approximately 0.1% of lymphoma cases (Pathology PMID31735345). Given its low incidence and aggressive clinical course, these patients are rarely captured in prospective studies or clinical trials; and while academic centers often lead efforts in rare lymphoma research, outcomes across facility types remain poorly understood. Although some factors for inferior survival outcomes have been identified, including poor performance status and Human Immunodeficiency Virus (HIV) co-infection, further characterization of these needs to take place (Medicine PMID3811535). To our knowledge, this is the largest study analyzing outcomes in patients with HHV8+ DLBCL comparing sociodemographic factors, disease characteristics, and survival outcomes between academic cancer programs (ACP) and community cancer programs (CCP).
Methods A retrospective analysis of cases diagnosed with HHV8+ DLBCL in the United States reported to the National Cancer Database from 2004-2022 was carried out. ACP included Academic and Research Programs, including NCI-designated Comprehensive Cancer Centers. CCP included Community Cancer Programs, Comprehensive Community Cancer Programs, and Integrated Network Cancer Programs. Kaplan-Meier and Cox regression analyses were used to compare overall survival (OS) between the two cohorts. Variables used for adjustment included age, ethnicity, insurance status, distance from hospital, and Charlson-Deyo comorbidity score.
Results A total of 228 patients with HHV8+ DLBCL were identified: 123 received care at ACP and 89 at CCP. 70 patients had missing information regarding treatment facility and therefore, not included in the analysis. The majority of patients were male for both centers, 72% for ACP and 67% for CCP. The median age at presentation in ACP was 58 years vs 65 years for CCP [P<0.001]. Most of the patients were diagnosed in the age group of <50 years, for ACP it represented 55% and for CCP 43% [P<0.001].
The most frequent ethnicity in both groups were non-Hispanics, with a predominance of race of Whites followed by Blacks. Regarding insurance status, Medicare was the most common among ACP (39%) and CCP (53%), followed by private insurance 37% and 34%, respectively [P<0.001].
Clinical characteristics at diagnosis demonstrated that 29% of ACP had a Charlson-Deyo comorbidity score ≥2, compared to 25% in CCP. Stage IV was the most frequent stage at diagnosis, for ACP representing 37% and CCP 30%. HIV positivity was significantly higher at ACP 20% vs 8% [P<0.001].
Geographic access to care, measured as median distance from residence to reporting facility in miles was 8 for ACP and 7 for CCP. Most of the patients in either facility received systemic therapy, 90% for ACP and 84% in CCP. The median time from diagnosis to initiation of treatment was 15 days in ACP vs 19 days in CCP [P<0.001].
The 2-, 5-, and 10-year survival probabilities for ACP vs CCP were 72% vs 60%, 66% vs 60%, and 50% vs 51%, respectively. After multivariate adjustment the median survival time was 10 years for ACP and not reached for CCP, with an OS not statistically significant [P=0.639].
Conclusion This represents the largest cohort analysis of HHV8-positive DLBCL to date and reveals striking disparities for patients with HIV co-infection, comparing sociodemographic and clinical characteristics and treatment facility type. Patients managed at ACP were more likely to be HIV-positive, uninsured and from racial and ethnic minority groups. While the difference in OS between ACP and CCP did not reach statistical significance, in the early years following the diagnosis the survival curve separates favoring ACP over CCP. These findings highlight the complexity of managing virally driven lymphomas and emphasizes the need to expand access to specialized, multidisciplinary care. Strengthening partnerships with ACP and CCP through joint development of protocols, standardization of treatment approaches, and implementation of supportive care and survivorship for patients among both institutions, may help close gaps in equity and improve outcomes for this vulnerable population.
