Clinical Experience with Venetoclax and Its Safety in Patients with Chronic Lymphocytic Leukemia in Later Lines of Treatment: A Multicenter Analysis from Slovakia

The treatment of chronic lymphocytic leukemia (CLL) has shifted from chemoimmuno-therapy to targeted therapy, resulting in improved outcomes and patient survival. The aim of this study was to evaluate the efficacy and safety of venetoclax-based regimens in patients with relapsed/refractory CLL, as well as their effectiveness in patients previously treated with ibrutinib. We retrospectively analyzed 98 patients with CLL who received venetoclax in the second or later lines of therapy in Slovakia between 2018 and 2024. The median age was 68 years, and treatment was administered either as monotherapy or in combination with rituximab. Response to treatment was assessed according to the iwCLL 2018 criteria and clinical practice. Survival outcomes were evaluated using Kaplan–Meier analysis. An overall response was achieved in the majority of patients, with 2% achieving complete remission, 65% incomplete complete remission and 32% partial remission. At a median follow-up of 34 months, median overall survival was not reached (mean 52.5 months), and median progression-free survival was 46 months. Patients previously treated with ibrutinib had significantly worse outcomes (p = 0.022). Adverse events were predominantly hematological (64%), with 19% being grade 3–4. Venetoclax-based regimens represent an effective and well-tolerated treatment optionfor relapsed/refractory CLL, including in patients previously treated with ibrutinib, with acceptable and manageable toxicity.