The impact of prior malignancies on the development of second malignancies and survival in follicular lymphoma: A population‐based study

Manette A.W Dinnessen,Otto Visser,Pieternella J Lugtenburg,Nicole M.A Blijlevens,Sanne H Tonino,Marie José Kersten,Avinash G Dinmohamed,Marjolein W.M Van Der Poel

doi:10.1002/jha2.108

Abstract

We assessed the impact of a prior malignancy diagnosis (PMD) – as a potential proxy for genetic cancer susceptibility – on the development of a second primary malignancy (SPM) and mortality in follicular lymphoma (FL) patients. From the nationwide Netherlands Cancer Registry, we selected all adult FL patients diagnosed in 1994‐2012 (n = 8028) and PMDs and SPMs relative to FL, with follow‐up until 2017. We constructed two Fine and Gray models – with death as a competing risk – to assess the association between a PMD and SPM incidence. A PMD was associated with an increased incidence of SPMs (subdistribution hazard ratio [SHR], 1.30; 95% confidence interval [CI], 1.03‐1.64) – especially carcinomas of the respiratory tract (SHR, 1.83; 95% CI, 1.10‐3.05) and cutaneous squamous cell carcinomas (SHR, 1.58; 95% CI, 1.01‐2.45) – and a higher risk of mortality in a multivariable model (HR, 1.43; 95% CI, 1.19‐1.71). However, when additionally adjusted for the receipt of systemic therapy and/or radiotherapy before FL diagnosis, only patients who received such therapies had an increased incidence of SPMs (SHR, 1.40; 95% CI, 1.02‐1.93). In conclusion, patients with a PMD had a higher rate of SPMs and mortality than those without a PMD, which might have resulted from therapy‐related carcinogenesis.

Highlights

Advances in the diagnosis and management of follicular lymphoma (FL) – most notably the introduction of rituximab – have considerably improved the survival of patients with FL over the past decades [1,2,3,4,5,6,7,8,9]
In the univariable Fine and Gray regression model with prior malignancy diagnosis (PMD) regarded as a binary variable, a PMD was associated with an increased incidence of second primary malignancy (SPM) (SHR, 1.44; 95% CI, 1.151.80; P = 0.001; Table 2)
Subgroup analyses revealed a higher incidence for carcinomas of the respiratory tract (SHR, 1.91; 95% CI, 1.163.15; P = 0.011) and squamous cell carcinomas (SHR, 2.02; 95% CI, 1.31-3.12; P = 0.001; Supplemental Table 2)

Summary

Introduction

Advances in the diagnosis and management of follicular lymphoma (FL) – most notably the introduction of rituximab – have considerably improved the survival of patients with FL over the past decades [1,2,3,4,5,6,7,8,9]. In the present chemoimmunotherapy era, 5-year relative survival rates for newly diagnosed patients with FL range between 41% and 95%, depending on the sex, race, age, disease stage, and geographical location [5,6,8,9,10,11]. A few studies have reported an increased risk of hematological and solid SPMs among patients with FL, as compared to the general population [12,13,14]. Suggested risk factors for SPMs among patients with FL [12,13,14] and non-Hodgkin lymphoma in general, included age > 65 years, male sex, and receipt of radio- and/or chemotherapy for the lymphoma [15]

Methods

Results

Conclusion