Real-World Outcome of Treatment with Single-Agent Ibrutinib in Italian Patients with Chronic Lymphocytic Leukemia: Final Results of the EVIdeNCE Study

Simple Summary In clinical trials, ibrutinib was found to be effective and well-tolerated in patients with chronic lymphocytic leukemia (CLL). To confirm these findings, data on unselected patients treated in clinical practice are necessary. The aim of our observational, prospective Italian cohort study was to describe the real-world persistence rate, patterns of use, and clinical outcomes in patients with CLL treated with single-agent ibrutinib across various treatment lines. We found that, despite the high burden of patient comorbidities and unfavorable genetic features, the majority of patients (217/309, 70%), especially those treated in first line (75%), continued ibrutinib treatment for >= 2 years. The most common reasons for treatment discontinuation were adverse events, primarily infections. We reported positive clinical and survival outcomes, especially in the first-line cohort, and a safety profile consistent with clinical trial data. Our data suggest that ibrutinib is a valuable option for both treatment-naive and previously treated patients with CLL.Abstract Real-world data in clinical practice are needed to confirm the efficacy and safety that ibrutinib has demonstrated in clinical trials of patients with chronic lymphocytic leukemia (CLL). We described the real-world persistence rate, patterns of use, and clinical outcomes in 309 patients with CLL receiving single-agent ibrutinib in first line (1L, n = 118), 2L (n = 127) and >= 3L (n = 64) in the prospective, real-world, Italian EVIdeNCE study. After a median follow-up of 23.9 months, 29.8% of patients discontinued ibrutinib (1L: 24.6%, 2L: 29.9%, >= 3L: 39.1%), mainly owing to adverse events (AEs)/toxicity (14.2%). The most common AEs leading to discontinuation were infections (1L, >= 3L) and cardiac events (2L). The 2-year retention rate was 70.2% in the whole cohort (1L: 75.4%, 2L: 70.1%, >= 3L: 60.9%). The 2-year PFS and OS were, respectively, 85.4% and 91.7% in 1L, 80.0% and 86.2% in 2L, and 70.1% and 80.0% in >= 3L. Cardiovascular conditions did not impact patients' clinical outcomes. The most common AEs were infections (30.7%), bleeding (12.9%), fatigue (10.0%), and neutropenia (9.7%), while grade 3-4 atrial fibrillation occurred in 3.9% of patients. No new safety signals were detected. These results strongly support ibrutinib as a valuable treatment option for CLL.