Risk Factors Associated with Earlier Relapse and Death and Treatment Response in Patients with Follicular Lymphoma in Taiwan
Authors: Pei Sung-Nan , Huang Kuan-Chih , Wang Ming-Chung , Kuo Ching-Yuan , Ma Ming-Chun , Liao Chun-Kai , Rothwell Lee Anne , Qiu Hong , Liu Yanfang 
Published: October 2019

Abstract
Background: Follicular Lymphoma (FL) has been relatively uncommon in Asia. Information on prognostic risk factors are scarce in the Asian population. We evaluated patients with FL in a tertiary medical center in Taiwan to gain better understanding of real world treatment and risk factors affecting outcome.
Purpose: To evaluate clinical outcomes and risk factors associated with outcome in patients with FL in Taiwan.
Methods: We conducted a retrospective cohort study using electronic medical records from Kaohsiung Chang Gung Memorial Hospital, a major regional hospital in southern Taiwan, from 01 January 2008 to 31 December 2017. Newly diagnosed patients with FL were enrolled from 01 Jan 2008 to 31 Dec 2013. All eligible patients were followed-up until study end, loss to follow-up or until death, whichever occurred first. Event-free survival (EFS) and overall survival (OS) were calculated using the Kaplan-Meier method. Risk factors of EFS and OS were identified using Cox proportional hazards model. A significant association was set at p<0.01.
Results: A total of 67 patients with newly diagnosed FL were included in the cohort analysis, accounting for 13.7% (67/489) patients with B cell non-Hodgkin lymphoma during the enrolment period. Median follow-up time was 60 months. At diagnosis, median age was 58 years (range 28-95), 56.7% (38/67) of patients were female, and 68.7% (46/67) had Stage III-IV disease. There were 37.3% (25/67) of patients with bone marrow involvement and 22.4% (15/67) with involvement of more than one extra-nodal site. The percentage of patients with low, intermediate and high-risk FL was 32.8%, 25.4%, 38.8%, respectively by FLIPI-1, and 13.4%, 44.8%, 26.9% by FLIPI-2.
72% (48/67) of patients received first-line treatment with regimens that included rituximab, cyclophosphamide, vincristine, prednisolone ± doxorubicin. Of these, 54.2% (26/48) of patients demonstrated complete response and 37.5% (18/48) had a partial response. A further 22.4% (15/67) patients received other treatments and 6.0% (4/67) patients did not receive any treatment. Progression of disease within 24 months after commencing treatment occurred in 32.8% of patients. The 5-year EFS and OS for all patients were 48.6% and 76.2%, respectively (Figure).
A higher relapse rate was associated with the presence of B symptoms (HR 6.1; 95% confidence interval [CI] 2.8-13.2), ECOG score ≥2 (HR 5.7; 95% CI 1.7-19.6), FLIPI-2 score ≥3 (HR 5.5; 95% CI 1.4-20.6), large cell transformation (HR 4.1; 95% CI 1.66-10.6), elevated β2 microglobulin (HR 4.0; 95% CI 1.8-9.1), age >70 years (HR 3.6; 95% CI 1.7-7.5), involvement of more than one extra-nodal site (HR 3.5; 95% CI 1.6-7.6) and elevated LDH (HR 2.5; 95% CI 1.3-5.1) (Table 2).
Conclusion: Most patients with FL in this tertiary center in Taiwan were at an advanced disease stage at diagnosis. While the majority responded to conventional chemotherapy, one-half of patients progressed within 5 years. Involvement of extra-nodal sites, B symptoms, older age (>70) higher FLIPI-2 score, elevated β2 microglobulin and ECOG score ≥2 were identified as risk factors for earlier relapse and death.

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