The Evolution of Treatments and Outcomes for Real-World Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma in a Chinese National Medical Center: Over 10 Years of Experience with 370 Patients
Authors: An Ran , Jin Wen , Weng Xiangqin , Wang Kankan , Zhang Sujiang , Chen Li , Mi Jianqing 
Published: December 2024

Background:
Over the past decade, there have been significant changes in the treatment landscape for chronic lymphocytic leukemia/Small Lymphocytic Lymphoma (CLL/SLL). These advancements have not only improved patient outcomes but also significantly altered our therapeutic goals for this disease.
Aims:
Evaluation of real-world outcomes for CLL/SLL patients in China as treatment strategies evolve.
Methods:
Demographic data, clinical characteristics, treatment and survival were retrospectively collected for CLL/SLL patients hospitalized in our center from February 2014 to October 2023.
Results：
The study cohort included 370 CLL/SLL patients, with the earliest onset year tracing back to 2000. There were 265 males and 105 females. At the time of admission, the median age was 66 years (range 29-89), and 193 patients (52%) were older than 65 years. A total of 139 individuals (38%) were classified as high-risk based on the Rai (III, IV) or Binet (C) staging system. Since 2020, fluorescence in situ hybridization (FISH) has been implemented for CLL/SLL patients in our center, resulting in 182 patients undergoing the test. Genomic abnormalities were detected in 124 (68%) of these patients: 49 (27%) had Trisomy 12, 34 (19%) had an RB1 deletion, 18 (10%) had an ATM deletion, and 13 (7%) had a TP53 deletion. IGHV mutation was present in 71% (80 out of 113) of the patients.
There were 298 patients (81%) who had indications for treatment and received therapy. The median time to first treatment (TTFT) was 14 months (range 0-192 months). Among these, 11 patients experienced Richter transformation (RT) at the time of first treatment. Of the remaining 287 patients, 74 (26%) were treated with alkylating or nucleoside agents (CT), 74 (26%) received chemoimmunotherapy (CIT), and 139 (48%) were administered Bruton's tyrosine kinase inhibitors (BTKi) either as monotherapy or in combination therapy. Before 2018, first-line treatments for CLL/SLL primarily included CT and CIT, accounting for 54% and 43% of the 84 treated patients, respectively. Only 3 patients received ibrutinib as part of a clinical trial. However, since 2018, with the sequential approval of BTKi such as ibrutinib, zanubrutinib, and orelabrutinib in China, the proportion of patients receiving CT (14%) and CIT (19%) among the 203 patients has significantly decreased. Instead, a growing number of patients (67%) have been treated primarily with BTKi.
With a median follow-up of 46.8 months (range 0.2-254.6 months) from the diagnosis of the disease, the estimated 18-year overall survival (OS) rate for all patients was 66%. For patients receiving first-line treatment (excluding the 11 mentioned with RT), the median follow-up times were 33 months for the CT group, 37 months for the CIT group, and 17 months for the BTKi group. The estimated 7-year OS rates for these three groups were 77%, 80%, and 71% (p=0.473), respectively. The 7-year progression-free survival (PFS) rates were 42%, 63%, and 72% (p=0.111), respectively. Our data suggest that BTKi-based treatment strategies can achieve better PFS, but there was no statistically significant difference compared to the CT and CIT groups. This may be due to the fact that most CT and CIT patients started treatment earlier and were more likely to be lost to follow-up, thereby underestimating the occurrence of PFS events.
Including the 11 RT patients mentioned earlier, a total of 19 patients developed RT. Among these, 13 cases were diffuse large B-cell lymphoma, 2 were mantle cell lymphoma, 2 were Hodgkin lymphoma, 1 was B-cell prolymphocytic leukemia, and 1 was angioimmunoblastic T-cell lymphoma. The median time from disease onset to transformation was 34 months (range 1-221 months). The 18-year OS rates for patients with and without RT were 25% and 70% (p=0.008), respectively.
Conclusion：
This real-world study demonstrates significant advancements in the treatment of CLL/SLL over the past decade. The introduction and inclusion of BTKi in China's healthcare insurance policy have notably shifted treatment practices from CT and CIT to BTKi-based therapies. This transition has improved patient outcomes and prognosis. Due to the convenience of oral administration, an increasing number of patients are opting for BTKi as their first-line treatment.