PF486 THE IMPACT OF PRIOR MALIGNANCIES ON THE DEVELOPMENT OF SECOND MALIGNANCIES AND SURVIVAL IN PATIENTS WITH FOLLICULAR LYMPHOMA: A NATIONWIDE POPULATION‐BASED STUDY IN THE NETHERLANDS
Authors: M. Dinnessen, O. Visser, S. Tonino, M. van der Poel, N. Blijlevens, M.J. Kersten, P. Lugtenburg, A. Dinmohamed
Journal: HemaSphere (2019)

Background: Advances in the treatment of follicular lymphoma (FL) have considerably improved survival in FL. This success, however, might come at price, as FL patients correspondingly life long enough to potentially develop second primary malignancies (SPMs). A prior study among multiple myeloma (MM) factorpatients showed that a prior malignancy diagnosis (PMD) 3/4 as potential proxy for genetic susceptibility to cancer 3/4 was associated with SPM development and mortality after MM diagnosis (Jonsdottir, Blood Adv , 2017). At present, information on the impact of a PMD on the development of a SPM and mortality in FL is lacking. Aims: The aim of this nationwide population‐based study was to assess the impact of a PMD on the development of a SPM and survival in patients with FL in the Netherlands. Methods: We selected all adult FL patients diagnosed between 1994–2012 from the Netherlands Cancer Registry (NCR). PMDs and SPMs (excluding basal cell carcinoma) relative to FL were identified from the NCR and classified into subgroups as per the third edition of the International Classification of Diseases for Oncology (Fig 1A). Synchronous malignancies diagnosed within a time‐interval of 6 months prior to or after FL diagnosis (n = 300) were excluded. We used competing risk regression as per Fine and Gray 3/4 with death as a competing risk 3/4 to estimate sub‐distribution hazard ratios (SHRs) with 95% CIs for the association between a PMD before FL diagnosis and the development of a first SPM after FL diagnosis. These associations were also calculated for subgroups of SPMs. Cox regression was used to calculate hazard ratios (HRs) with 95% CIs to assess the risk of death associated with a PMD. All patients were followed from date of FL diagnosis to date of first SPM, death, or end of follow‐up (February 1, 2017). We adjusted all analyses for baseline characteristics at FL diagnosis (i.e. sex, year of diagnosis, age, and disease stage). Further, we examined the effect of additional adjustment for anti‐neoplastic therapy of PMDs and FL treatment started within one year after diagnosis (chemotherapy, radiotherapy only, no therapy, other therapy) on the effect estimates for a PMD. A P &lt; 0.05 indicated statistical significance. Results: We included 9,251 patients, of whom 672 (8.1%) had ≥1 PMD. At a median follow‐up of 6.9 years (range &lt;0.1–23.0), patients with a PMD developed a SPM more often than patients without a PMD (23% v 15%; P &lt; 0.001). Further, patients with a PMD were older at FL diagnosis (median age, 70 v 60 years; P &lt; 0.001) and more often female (50% v 42%; P &lt; 0.001). Overall, a PMD was associated with an increased rate of a SPM (Fig 1B), with an adjusted SHR of 1.67 (95% CI 1.39–2.00; P &lt; 0.001). This association was statistically significant for the following subgroups of SPMs: breast‐ and lung cancer and melanomas and squamous cell carcinomas of the skin ( P &lt; 0.05). Further, a PMD was associated with an increased risk of death (adjusted HR, 1.19; 95% CI, 1.07–1.33; P &lt; 0.001). The increased rate of SPMs and risk of death associated with a PMD was irrespective of the type of therapy applied for PMDs or FL, as additional adjustment for these factors did not affect the effect estimates. Summary/Conclusion: We demonstrated an association between a PMD and the development of a SPM and survival among patients with FL. Since additional adjustment for therapy did not alter the direction or magnitude of these associations, our results might suggest a role for genetic susceptibility to cancer. We encourage future studies to corroborate on the association between a PMD and SPM development in FL. image