Clinical experience and safety of venetoclax in the treatment of patients with chronic lymphocytic leukemia in second and subsequent lines of therapy: Real-world data fron hemato-oncology centers  of slovakia Free

Introduction: The treatment landscape for chronic lymphocytic leukemia (CLL) has significantly evolved in recent years, transitioning from standard chemoimmunotherapy to targeted therapies with novel agents. Clinical trials have demonstrated improved efficacy and overall survival with these agents. However, question remain regarding treaatment sequencing, particularly the effectiveness of venetocalx in patients who have previosly recieved targeted therapies in earlier lines. The primary objective of this study was to evaluate the efficacy (maximum response) and safety of venetoclax-based regimens in secnd-line and later-line settings in patients with CLL treated at hemaology centers in Slovakia. the secondary objective was to asses the effectiveness of venetoclax in patients previously treated with ibrutinib.

Methods: This retrospective analysis included 98 patients with CLL treated with venetoclax in second-line or subsequent lines of therapy across hematology centers in Slovakia from 2018 to 2024. Venetoclax was administered as monotherapy or in combination with rituximab. The median age at venetoclax initiation was 68 years (range: 49-83 years); 65 patients (66%) were male and 33(34%) female. Of these, 48 patients (49%) had prior exposure to ibrutinib. Treatment response and indications were assessed according to the 2018 International Workshop on CLL (iwCLL) criteria. Patients were evaluated after a minimum of two months of therapy until disease progression. Response was assessed via clinical evaluation, imaging (ultrasound or CT), and laboratory parameters. Bone marrow biopsies were not routinely performed. Adverse events were recorded based on CTCAE v5.0. Data were analyzed using descriptive statistics. Kaplan-Meier curves were used for overall survival (OS) and progression-free survival (PFS). Statistical comparisons used Chi-square, t-test, Mann-Whitney U, and Log-Rank test with a significance level of α = 0.05.

Resutls: Venetoclax, both as monotherapy and in combination with rituximab, demonstrated high efficacy and an acceptable safety profile in patients with relapsed/refractory CLL. The overall response rate (ORR) was high: 67% patients achieved an unconfirmed complete remission (uCR), 32% patients achieved partial remission (PR), and 1 (1%) had no response. The median follow-up was 34 months. Median PFS was 46 months; median OS was not reached, with an estimated mean OS of 52.5 months. Paients previously treated with ibrutinib had significantly worse outcomes (p = 0.022): uCR in 56%, PR in 42%, with a median OS of 46 months vs 56 months and PFS of 40.6 months vs 48.8 months, compared to patients without prior ibrutinib exposure. These patients had a higher median number of prior treatment lines (3 vs 1.8) and were older (70 vs 66 years). Hematologic adverse events occured in 64% of patients (19% were grade 3-4); non- hematologic adverse events occured in 42%, though severity was not routinely graded.

Conclusion: Our real-world data confirm that venetoclax-based regimens are highly effective and well tolerated in second-line and subsequent treatments of CLL, including in ptients previously treated with ibrutinib. Toxicity was manageable in the outpatient setting, with good treatment adherence and minimal need for hospitalization. these findings align with clinical trial data and support the continued intigration of venetoclax into the CLL treatment paradigm, offering patinets improved quality of life by avoiding the broader toxicity of traditional chemotherapy.