Trends in Incidence and Survival of Patients with Primary Effusion Lymphoma in the United States

Introduction: Primary effusion lymphoma (PEL) is a rare type of B-cell non-Hodgkin lymphoma that was first classified by the World Health Organization (WHO) in 2001. PEL is commonly associated with HIV infection, but non-HIV associated cases occur as well. The prognosis is poor, with 5-year overall survival of 17% reported in previous studies (El-Fattah MA, Hematol Oncol, 2017). However, these studies have not taken into account the recent advances in the treatment of PEL. Hence, we sought to evaluate whether the incidence and survival of patients with PEL has changed in the contemporary time period.

Method: We performed a population-based cohort study of patients with PEL diagnosed in the US between 2001-2021 using the Surveillance, Epidemiology, and End Results-17 database. We included patients with pathologically confirmed PEL and excluded patients who were diagnosed by autopsy or death certificate. We estimated age-adjusted incidence rates and calculated annual percent changes (APCs) using joinpoint regression. The study outcomes were relative survival (RS) and overall survival (OS), estimated using flexible parametric survival models. The primary exposure was period of diagnosis (2001-2010 vs 2011-2021). These periods were chosen based on a literature review to reflect the wider use of the dose-adjusted (DA)-EPOCH regimen (etoposide, prednisone, vincristine, cyclophosphamide and doxorubicin) after 2010. Covariates were age at diagnosis, sex, race, and documented B symptoms at diagnosis. P-values less than 0.05 were considered statistically significant. Analyses were performed using STATA version 18.0.

Results: A total of 236 patients with PEL were included in the study (n=82 during the first period and n=154 during the second). Median follow-up was 6.25 years (95% CI, 4.5-7.8 years). The median age at diagnosis was 51 years (interquartile range, 41-68 years). There was a strong male predominance (n=208, 88%). Most patients were White (n=171, 73%). Age-adjusted incidence rates increased significantly from 2001-2007 (APC 24.31, p<0.001) and then stabilized from 2008-2021 (APC 0.85, p=0.76). The age-adjusted incidence rate (per 1,000,000 persons at risk) increased from 0.04 in 2001 to 0.17 in 2021. There was a dramatic improvement in the survival of patients since the early 2000s. Five-year RS improved from 21% (95% CI, 13-30%) to 37% (29-45%). Five-year OS improved from 18% (95% CI, 11-25%) to 32% (95% CI, 25-40%). Median OS improved from 4 months (95% CI, 2-6) to 12 months (95% CI, 5-20). On multivariable analysis after adjustment for age, sex, race, and B symptoms, patients diagnosed in the most recent time period had a 49% lower excess mortality rate (adjusted hazard ratio, 0.61; 95% CI, 0.41-0.91; p=0.02).

Conclusion: The incidence of PEL increased in the early 2000s but has stabilized since that time. There has been a significant improvement in the survival of these patients in the last decade, likely due to therapeutic advancements including increased use of the DA-EPOCH regimen, better supportive care, and advances in the treatment of HIV (Epperla N, Cancer Med, 2020). Despite this improvement, the OS continues to remain poor (median OS of 12 months) representing an unmet need. Our findings underscore the need for prioritizing these patients to clinical trials with novel therapies.