Efficacy and prognostic determinants of BTK inhibitors in chronic lymphocytic leukemia (CLL): A real-world single-center cohort study from China

Abstract Background CLL is the most common adult leukemia in Western countries, with a rising incidence in China. Bruton's tyrosine kinase (BTK) inhibitors, such as ibrutinib and zanubrutinib, have revolutionized CLL treatment by improving progression-free survival (PFS) and overall survival (OS). However, real-world data on their efficacy and prognostic determinants, particularly in Chinese populations, remain limited. Previous studies suggest that factors such as TP53 mutations, del(17p), and complex karyotype influence BTK inhibitor responses. This study evaluates the real-world outcomes and prognostic factors in Chinese CLL patients treated with BTK inhibitors. Methods We conducted a retrospective cohort study of CLL patients treated with BTK inhibitors at Nanfang Hospital, Southern Medical University, between 2014 and 2024. Eligible patients were adults (≥18 years) with a confirmed diagnosis of CLL per the International Workshop on Chronic Lymphocytic Leukemia (iwCLL) criteria. Patients who received at least one dose of a BTKi were included. Exclusion criteria comprised prior BTKi therapy, or incomplete clinical data. Demographic, clinical, and laboratory data were extracted from electronic medical records, including baseline characteristics, disease-related factors, and treatment details, Outcome measures include progression-free survival (PFS), and overall survival (OS). PFS was defined as time from BTKi initiation to progression or death; OS as time from BTKi initiation to death from any cause. Survival curves were estimated via Kaplan-Meier method and compared using log-rank tests. Results Among 84 patients (median age 57 years; 61.9% male) enrolled, 56% (47/84) had advanced-stage disease. Baseline characteristics showed that first-line BTK inhibitor treatment was administered to 71.4% (60/84). High-risk features included complex karyotype (42.4%, 14/33), TP53 mutations (30.3%, 10/33), and trisomy 12 (32.4%, 11/34). After a median follow-up of 1.8 years (95% CI 1.4–2.3), median PFS and OS were not reached. Survival rates were: PFS, 1-year PFS 97.0% (95%CI 92.9-100%), 3-year PFS 84.9% (74.8-96.4%), and 5-year PFS 80.7% (68.6-94.8%), as for OS, 1 -year OS is 97.0% (95%CI 93%-100%), 3 -year survival is 90.7% [(95%CI 81.8%-100.00%), and 5 -year OS is 85.9% (95%CI 74.1%-99.61%)， no significant difference in PFS between first line (n=60) and relapsed/refractory (n=24) populations (HR 0.79, 95%CI 0.19-3.30; p=0.742), with 3-year PFS rates of 86.3% vs 82.0%, respectively. OS analysis shows the same trend (HR 0.75, 95%CI 0.12-4.5; p=0.749). Subgroup analyses demonstrated that high-risk genomic features significantly impacted outcomes, with TP53 mutations (p=0.003), complex karyotype (p=0.034), and del(17p) (p=0.013) all associated with inferior PFS, while only del(17p) remained predictive of worse OS in the analysis. Notably, treatment suspension was linked to significantly worse OS (p < 0.001) but not PFS compared to patients with dose suspension. Other evaluated factors - including del(13q), del(11q), dose reduction, and IGHV mutation status (≥2% cutoff) - showed no significant association with either PFS or OS outcomes. Conclusions This real-world study demonstrates that BTK inhibitors provide durable long-term efficacy in Chinese CLL patients, with 5-year PFS (80.7%) and OS (85.9%) rates. Notably, outcomes were comparable between first line and relapsed/refractory settings, reinforcing BTK inhibitors as a robust treatment option regardless of prior therapy. However, high-risk genomic features—including TP53 mutations, complex karyotype, and del(17p)—were associated with inferior PFS, while del(17p) also predicted worse OS. BTKi suspension negatively impacted OS, emphasizing the importance of treatment adherence. Further studies with larger cohorts and longer follow-up are warranted to refine risk stratification and optimize treatment approaches.