Characteristics and Treatment Response of Newly Diagnosed Advanced-Stage and Relapsed/Refractory Hodgkin Lymphoma in Taiwan: A Nationwide Retrospective Study
Authors: Teng Chieh-Lin Jerry , Tan Tran-Der , Lin Yu-Wen , Lien Pei-Wen , Chou Hsin-Chun , Lin Fang-Ju 
Published: February 2021

Background
Hodgkin lymphoma (HL) is a highly curable hematological neoplasm, even in an advanced stage. However, despite improvements in treatment, patients with primary refractory and/or relapsed HL (RRHL) still have a poor prognosis. Because of relatively low incidence, studies focusing on the clinical characteristics or outcomes for patients with advanced-stage HL and RRHL in Asia are few. The present study aimed to describe the clinical features and survival of these patients in Taiwan using a nationwide database.
Methods
This retrospective descriptive study was conducted by using the Taiwan Cancer Registry and the National Health Insurance Research Database. All newly diagnosed HL patients who started frontline treatment with an intent to cure were enrolled from 2009 to 2016. Patients who had an advanced-stage disease (i.e., stage III/IV) at diagnosis were identified. All chemotherapy agents prescribed during the 60-day period after the date of first treatment were considered as the same line regimen. Patients with RRHL were identified as those receiving a new chemotherapy for HL (across stages) other than the first-line regimen or undergoing an autologous stem cell transplantation (ASCT) at any time. We described the first-line regimens for newly diagnosed advanced-stage HL and salvage therapy for RRHL. Characteristics and survival outcomes, including overall survival (OS) and time to next treatment (TTNT, as a surrogate for progression-free survival, PFS), were further analyzed for patients who received ABVD or ABVD-like (BVD and AVD) regimen as the first-line treatment, specifically in those with advanced stage at diagnosis and RRHL patients who received ASCT.
Results
Between 2009 and 2016, 1,156 newly diagnosed HL patients with an intent-to-cure treatment were enrolled; of whom 490 were advanced stage at diagnosis. A bimodal age distribution with peaks around 20-44 and after 65 years was observed. Among the patients with an advanced stage disease, ABVD was the dominant frontline regimen, accounting for 79% of treated HL cases, followed by ABVD-like regimens (15%), and BEACOPP (3%). The median age of patients receiving ABVD/ABVD-like regimen was 34 years, and 62% were male. Over half of the patients were stage IV (57%), having extra-nodal disease (58%), and/or B-symptoms (54%). Only 19% of them received radiotherapy along with chemotherapy. With a median follow-up of 4.7 years, the OS and PFS rates were 76% and 52%, respectively. Among 321 RRHL patients, 288 had received ABVD/ABVD-like regimens as frontline therapy. In this 288-patient cohort, 135 (47%) proceeded to ASCT. Among these 135 patients, ESHAP was the commonest salvage therapy (62%), followed by ICE (15%), and others (7%). After a 3.9-year median follow-up, the OS and PFS rates were 76% and 47%, respectively.
Discussion
The current study describes the clinical characteristics and treatment outcomes of patients with advanced-stage HL and RRHL in Taiwan. Prior studies describing clinical features and outcomes of HL patients in Taiwan are limited to a single medical center experience. Our study provides nationwide data and suggests the clinical features of advanced-stage HL patients are not much different from those in Western countries. Though the OS of advanced-stage HL remained high, half of the patients who received standard treatment developed relapsed/refractory disease, suggesting a strong unmet need for better novel therapies. Among the RRHL patients receiving ASCT, about half of them experienced further disease progression, and a quarter died afterwards. This observation highlights the importance of identifying high-risk patients for progression. Moreover, regimens that include novel agents may improve the outcomes of early high-risk patients. Further studies are needed to determine the real-world treatment outcomes and cost-effectiveness of these novel agents.
Conclusion
The characteristics of advanced-stage HL in Taiwan were comparable to those in Western countries. Considering the poor prognosis of RRHL, it is crucial to identify patients with a high risk of progression in the first line so that we can optimize their treatment outcomes.

Disclosures
Lien: Takeda Pharmaceuticals Taiwan: Ended employment in the past 24 months. Chou:Takeda Pharmaceuticals Taiwan: Current Employment. Lin:Takeda Pharmaceuticals Taiwan: Research Funding.