Interim results of an multicenter observational clinical study on treatment strategies for chronic lymphocytic leukemia/small lymphocytic lymphoma in Russia

Aim. To evaluate the survival rates in patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) in routine clinical practice in Russia and to analyze the impact of clinical and demographic factors on therapy selection and treatment outcomes.

Materials and methods. An observational study of CLL/SLL treatment strategies has been conducted in 34 centers in Russia from 2021 to the present. Effectiveness was assessed based on survival rates, clinical characteristics, and therapeutic approaches. Statistical analysis included descriptive methods and Kaplan–Meier curves for survival outcomes. Cox proportional hazards models were used to assess the influence of various factors on progression-free survival (PFS).

Results. As of the interim analysis (2021–2024), a total of 2,094 patients were included in the study. The majority of the cohort consisted of male patients (54.11%) aged ≥ 65 years (59.8%). Most patients (77.94%) had a favorable performance status of 0–1 according to the ECOG scale. Among molecular-genetic alterations, wild-type TP53 (86.43%) and IGHV (69.27%) were most commonly observed. According to the analysis of treatment data, the most frequently prescribed combinations were FCR (22.32%) and RB (18.67%). In later treatment lines, the proportion of targeted therapies increased. Overall survival among 1654 patients with known treatment start date remained high throughout 10 years of follow-up, and was 93.88% by year 10. Progression-free survival (PFS) was assessed for all patients receiving first-line therapy, including retrospective data. PFS was assessed separately for the second and subsequent lines by type of therapy. PFS among patients who received first-line therapy, regardless of the type of chemotherapy and the presence of TP53/IGHV mutation after 5 years was 76.93%. PFS in the targeted therapy group in patients who received the third, fourth and subsequent lines of therapy was significantly higher than in the immunochemotherapy group (p = 0.001 and 0.009 respectively). According to the Cox model, among patients who received first-line therapy, a significant association of a reduced risk of progression with male gender was shown (HR 0.52, 95% CI 0.33–0.82; p < 0.005). There was a trend towards an association of TP53 mutation with a high risk of progression (HR 2.02, 95% CI 0.91–4.51; p = 0.084), but statistical significance was not achieved. In patients who received the third, fourth and subsequent lines of therapy, targeted therapy was significantly associated with a lower risk of progression (HR 0.16, 95% CI 0.05–0.53; p = 0.002 and HR 0.27, 95% CI 0.10–0.75; p = 0.012, respectively).

Conclusion. The interim analysis showed generally favorable PFS dynamics, but some subgroups of patients, e.g., those with TP53 mutation, demonstrated a less favorable prognosis. Targeted therapy was significantly associated with a lower risk of disease progression among patients receiving third, fourth, and subsequent lines of therapy. The obtained results confirm the data on the high efficiency of targeted therapy in the treatment of CLL/SLL, especially in patients with an aggressive course of the disease and unfavorable prognostic factors.