An Increasing Trend of Incidence, Prevalence and Mortality, and Occurrence of Second Primary Malignancies Among Patients with B-Cell Non-Hodgkin Lymphoma: A 10-Year Longitudinal Population-Based Retrospective Cohort Study in South Korea
Authors: Kim Jin Seok , Liu Yanfang , Ha Kyoung Hwa , Qiu Hong , Rothwell Lee Anne , Kim Yu Ri , Kim Hyeon Chang 
Published: October 2019

Abstract
Background: Information about the epidemiology, treatment and clinical outcome of patients with B-cell Non-Hodgkin Lymphoma (BNHL) are limited and fragmented across Asia. Disparities in economy, health-care infrastructure, and access/reimbursement to novel drugs mean that treatment options and outcomes vary across the region. There is a need for improved understanding of real world treatment practices and outcomes in BNHL in Asian countries.
Purpose: To describe incidence, clinical and treatment patterns and survival of patients with BNHL in South Korea.
Methods: We conducted a retrospective cohort study using claims data from the National Health Insurance Service that covers 98% of all residents in South Korea. Newly diagnosed patients aged ≥18 years with a confirmed diagnosis of BNHL during the period 01 January 2006 to 31 December 2015 were enrolled. All eligible patients were followed up until death, dis-enrolment or the end of the observational period (December 31, 2015), whichever occurred first. Patients with pre-existing primary cancers were excluded. Standardized annual incidence, prevalence and morality rates were estimated. Overall survival and occurrence of second primary malignancies were estimated using Kaplan-Meier methods.
Results: A total of 19,500 patients with newly diagnosed BNHL were included in the cohort analysis. At diagnosis, the mean age of patients was 59.5 years, 60.0% were 19-64 years of age and 54.0% were male. Diffuse large cell B-cell lymphoma (DLCBCL) was the most common diagnosis in each study year (53.1% to 58.7% of patients annually). The most commonly used first-line treatment regimens included rituximab-based combinations for the majority of patients with DLCBL, Follicular Lymphoma (FL), Mantle Cell Lymphoma (MCL), or Chronic lymphocytic leukemia/ Small Lymphocytic Lymphoma (CLL/SLL), radiation for patients with Marginal Zone Lymphoma (MZL), and chlorambucil or cyclophosphamide for patients with Waldenström's Macroglobulinemia (WM).
The overall incidence of BNHL increased over time, from 5.96 per 100,000 in 2011 to 6.99 per 100,000 population in (Table). BNHL prevalence increased steadily each year, and was 2.5-fold higher in 2015 than in 2011. The mortality rate increased by 50% over the same period, from 1.38 per 100,000 to 2.09 per 100,000 population. There was a trend of increasing incidence of some BNHL sub-types, mainly DLBCL, Follicular Lymphoma (FL), and Marginal Zone Lymphoma (MZL), over time (Fig. 1).
There were 4009 patients between 2006-2015 (20.6%) who were diagnosed with at least one second primary malignancy more than 180 days after their BNHL diagnosis. The majority (96%) had a solid tumor; incidence rate of 5.93 per 100 person-years versus 0.24 per 100 person-years for hematological malignancies. By year 5, the cumulative hazard for developing a second primary malignancy was highest for CLL/SLL (25%) and lowest (18%) for FL. By year 8-9, the cumulative risk of developing a second primary malignancy was similar among the BHNL sub-types (Fig. 2).
Five-year survival was 88% (95% Confidence interval [CI] 86-90) for MZL, 79% (95% CI 76-81) for FL, 62% (95% CI 59-66) for CLL/SLL, 60% (95% CI 59-61) for DLBCL, 54% (95% CI 47-63) for WM and 53% (95% CI 46-60) for MCL. Overall survival by year 9 was highest in patients with CLL/SLL and FL, lowest for WM (Fig. 3).
Conclusion: The incidence, prevalence and mortality of BNHL appears to be increasing in Korea, and the occurrence of second primary malignancies is high. BNHL remains an important unmet medical need in South Korea.

Disclosures
Liu: Janssen Research & Development, LLC: Employment, Equity Ownership. Qiu:Janssen Research & Development, LLC: Employment, Equity Ownership. Rothwell:Janssen Research & Development, LLC: Employment, Equity Ownership.