Abstract
Introduction: Follicular lymphoma (FL) is the most common subtype of indolent non-Hodgkin lymphoma in the US with approximately 14,000 cases diagnosed each year. The disease follows a relapsing-remitting course with an average 5-year relative survival of 90%. However, the prognosis is worse for patients who develop histologic transformation (HT) to large cell lymphoma. The objective of this study was to estimate the cumulative incidence and outcomes of transformed FL (tFL) in the US population using data from 18 state and local cancer registries.
Method: We conducted a population-based cohort study of FL in the US using the Surveillance, Epidemiology, and End Results-18 database. We included adults aged 18-84 years who were diagnosed with FL in the US between 2000-2018. We excluded individuals who were diagnosed by autopsy or death certificate and primary CNS lymphomas. We estimated the cumulative incidence of HT by following patients from their diagnosis of FL to their subsequent diagnosis of large cell lymphoma. We then estimated post-transformation relative survival and crude probability of death from tFL using flexible parametric survival models. We used a multivariable relative survival model to identify factors associated with excess mortality among patients with HT. We used the Bonferroni correction to adjust for multiple comparisons and P values < 0.005 were considered significant.
Results: A total of 53,980 patients were diagnosed with FL between 2000-2018. The median age at diagnosis was 63 years (interquartile range, 54-72). At a median follow-up of 6.9 years (IQR, 3.0-11.7), the cumulative incidence of HT was 2.5% (n=1,401) in the entire cohort. The cumulative incidence of HT was higher for patients with stage III-IV FL at diagnosis (n=827, 3.0%) compared to stage I-II disease (n=478, 2.1%). Most patients in the study were diagnosed with HT between 2012-2018 (n=1,168, 83%). Five-year post-transformation relative survival was 55% (95% CI, 52-59%) in the entire cohort and decreased with increasing age. Similarly, among patients with tFL, the crude probability of death from lymphoma increased with increasing age (Figure 1). However, on multivariable analysis, only male sex and stage III-IV disease were significantly associated with higher excess mortality after adjustment for multiple comparisons (Table 1).
Conclusion: In this large population-based study of tFL in the US, we found that patients with tFL continued to have poor outcomes despite advancements in treatment for B-cell lymphomas over the past two decades. Outcomes were worse for older patients and could be related to comorbidities and inability to tolerate/complete anthracycline-based chemotherapy regimens. On multivariable analysis, male sex and advanced stage were significantly associated with an inferior prognosis.
Disclosures
Epperla:Incyte: Speakers Bureau; Novartis: Honoraria; TG Therapeutics: Other: Ad Board; BeiGene: Other: Ad Board; Seattle Genetics: Other: Ad Board; Pharmacyclics: Other: Ad Board.
