Safety of Bruton kinase inhibitors in chronic lymphocytic leukemia: Real world clinical practice.

INTRODUCTION Bruton's tyrosine kinase inhibitors (BTKi) have replaced immunochemotherapy in patients with chronic lymphocytic leukemia (CLL). The safety profile, particularly in monotherapy indications under real-world clinical practice conditions, is key to optimizing outcomes.

OBJECTIVE To describe the safety and tolerability of continuous/indefinite BTKi therapy in patients with CLL treated in the first line and relapse/refractory (R/R) conditions with BTKi monotherapy, within labeled indications, at a tertiary care hospital.

METHODS Observational, retrospective, single-centre study including patients with CLL treated with iBTK (2015-2024). Demographic data, previous lines of treatment, dose adjustments and suspensions, and adverse events (AEs) by system and severity were recorded. Proportions were compared using Fisher's exact test. Treatment continuation was analyzed using Kaplan-Meier curves, log-rank tests, and Cox regression.

RESULTS Eighty-three patients (50.6% male) were included, with a mean age at diagnosis of 67.2 years. Forty-eight (58%) received iBTK as first-line therapy and 35 (42%) in R/R. The most commonly used iBTK was ibrutinib (62.5% in first-line and 88.6% in R/R). Median follow-up was 20.8 months. Overall, 28,9% required dose adjustment, with no differences between the two groups (p = 0.158). Treatment discontinuation was more frequent in patients with R/R patients (74.3% vs 39.6%; RR 1.81; 95% CI: 1.23-2.66; p = 0.002). AE were the most common reason for treatment discontinuation (15.7%). A total of 161 AEs were recorded, with infectious AE being the most frequent category. Respiratory infections were significantly more incident in R/R patients (p = 0.046). Patients with prior exposure to immunochemotherapy had an increased risk of treatment discontinuation (HR = 2.15; 95% CI: 1.18-3.89; p = 0.012).

CONCLUSIONS BTKi showed a manageable safety profile, with infections as the most common toxicity and secondary malignancies occurring at rates comparable to those reported in the literature. Treatment discontinuation was less frequent in the frontline setting, underscoring the influence of clinical context and prior therapies. Despite the limitations of a retrospective, single-centre design, this study provides information applicable to daily practice and highlights the importance of close follow-up to optimize both safety and treatment continuity.