1214 - An Investigation into the Differences between Western and Chinese population with Chronic Lymphocytic Leukemia

Introduction: The incidence of Chronic Lymphocytic Leukemia (CLL) is notably lower in Asian population, being 10- to 20-fold less than that in Western population. Previous research has indicated that CLL in China tend to be younger, exhibit more mutated immunoglobulin heavy-chain variable genes (IGHV), and possess a unique mutation landscape. However, there are few large series cohort to systematically illustrate difference of CLL between Chinese and Western population.

Methods: We analyzed clinical data from 2005 CLL patients treated at the Blood Diseases Hospital, Chinese Academy of Medical Sciences, from February 2000 to December 2020. Furthermore, we collected the Immunoglobulin heavy chain variable (IGHV) sequences of 1223 Chinese CLL patients and compared them to sequences from 7424 published CLL patients from Europe and the United States.

Results: The median patient age at diagnosis was 61 years (range 20-92), which is younger than Western CLL patients, who typically are 65-70 years old. Additionally, a larger proportion of our patients had Binet stage B or C at diagnosis (69.3%) compared to Western CLL patients (20%-40%).
Among 1476 patients with available treatment data, 1191 (80.7%) received treatment, which is a higher proportion than in Western countries. The time from diagnosis to first treatment (TTFT) was shorter than in Western countries, being 7.0 months (95% CI 4.1-9.9). Chemotherapy, immunochemotherapy, and targeted therapy constituted 69.1%, 14.4%, and 16.5% of first-line treatments, respectively, leading to varying overall response rates (ORR). After a median follow-up period of 76.0 months (95% CI 72.2-79.8), we observed certain progression free survival (PFS) and overall survival (OS) rates. The observed outcomes were similar to those reported in Western studies. As anticipated, patients receiving immunochemotherapy and targeted therapy showed better PFS and OS than those receiving chemotherapy.
Regarding cytogenetic abnormalities, we observed a lower proportion of RB1 deletion (20.9%) compared to Western countries, while the frequency of other cytogenetic abnormalities was similar. When compared to Western CLL, Chinese CLL showed a higher proportion of mutated IGHV, higher frequent usage of certain IGHV fragments, and lower frequent usage of others. Additionally, certain IGHD and IGHJ fragments were either more or less frequently used in Chinese CLL. Stereotyped BCR was found in 15.3% of CLL patients, which is less than in Western countries. Furthermore, the frequency of certain subsets was higher or lower in Chinese CLL compared to Western CLL.

Conclusions: This study, the largest real-world investigation involving Eastern CLL to date, provides an essential foundation for future clinical investigations of CLL in China. Despite patients being younger, having advanced stages at diagnosis, the outcomes did not deviate from those reported in Western studies. The biological difference may contribute to the discrepancy.