Risk of Second Primary Malignancies in Patients With Follicular Lymphoma: A United States Population-based Study

Follicular lymphoma (FL) is a common low-grade lymphoma with excellent long-term survival in the present era. We used the Surveillance, Epidemiology, and End Results registry to identify patients with FL from 1992 to 2010 and study the incidence and risk factors for the development of second primary malignancies (SPMs). During a median follow-up period of 71 months, 1540 patients (9.9%) developed SPMs, with a cumulative incidence of 11% at 10 years and an increased risk of both hematologic and solid malignancies. This risk was significantly increased among patients aged > 65 years, males, and those receiving radiation therapy. With the improving outcomes of patients with follicular lymphoma (FL), it is imperative to focus on survivorship issues, including the development of second primary malignancies (SPMs). We used a large US database to measure the risk of SPMs among FL survivors. We used the Surveillance, Epidemiology, and End Results-13 registry to identify FL patients from 1992 to 2011. We calculated the risk of SPMs, developing ≥ 6 months after diagnosis, using the standardized incidence ratio (SIR) and absolute excess risk. We calculated the cumulative incidence of SPMs using the competing risk method and risk factors for SPMs using univariate and multivariate methods. Of a total of 15,517 patients with FL followed up for a median of 71 months, 1540 (9.9%) developed SPMs, with a SIR of 1.08 and absolute excess risk of 11.3 per 10,000 person-years. A significantly increased risk was noted for Hodgkin lymphoma (SIR, 5.85), acute myeloid leukemia (SIR, 4.88), and the following sites: oral cavity and pharynx (SIR, 1.43), stomach (SIR, 1.43), lung and bronchus (SIR, 1.35), melanoma of skin (SIR, 1.38), other nonepithelial cancers of the skin (SIR, 2.88), urinary bladder (SIR, 1.24), and kidney/renal pelvis (SIR, 1.43). The cumulative incidence of SPMs was 11.06% at 10 years. Multivariate regression showed that age > 65 years (SIR, 1.57; P < .001), male gender (SIR, 1.43; P < .001), and receipt of radiation (SIR, 1.24; P = .001) predicted a higher rate of SPMs. Patients with FL have increased risk of both hematologic and solid malignancies. Risk factors for SPMs include advanced age, male gender, and receipt of radiation therapy.