Real-World Safety Profile of Ibrutinib in Chronic Lymphocytic Leukemia: A Focus on Adverse Events, Discontinuations, and Effectiveness Outcomes.

[BACKGROUND] Ibrutinib has transformed chronic lymphocytic leukemia (CLL) treatment, offering significant survival benefits in clinical trials. However, real-world evidence is essential to understand its safety and efficacy in broader patient populations.

[OBJECTIVE] To evaluate ibrutinib safety and effectiveness in a real-world cohort of CLL patients focusing on dose reductions, adverse events, and survival outcomes.

[METHODS] This single-center, retrospective, observational study of CLL patients treated with ibrutinib was conducted between January 2015 and June 2023. Data were retrieved from the IANUS electronic medical records including patient demographics, treatment indications, genetic markers, comorbidities, adverse events, and dose changes.

[RESULTS] This study involved 90 patients with a median age of 71.5 years. Most patients presented with advanced-stage disease (BINET C: 46%, RAI IV: 25%). Cardiovascular comorbidities were common (70%) and 11% had prior bleeding events. Severe adverse events (grade 3-4) occurred in most patients (60%) with infections (33.3%) and neutropenia (14.4%) being the most common. Dose reductions were required in 11.1% of patients mainly due to hematological toxicities and 22% discontinued treatment due to adverse events. However, dose reductions and severe adverse events did not significantly affect overall survival or progression-free survival. The overall response rate was 82.2%, with 42.2% achieving complete remission. Multivariate analysis identified age and comorbidities as significant predictors of severe adverse events but not survival outcomes.

[CONCLUSION AND RELEVANCE] Ibrutinib remains an effective treatment for lymphocytic leukemia, even in patients with comorbidities and high-risk genetic characteristics. The study supports dose adjustment as a viable strategy for managing toxicities without compromising efficacy. These findings highlight the need for personalized care and proactive management of adverse events in clinical practice, particularly in elderly patients or those with multiple comorbidities. Long-term clinical studies are essential to refine treatment strategies and improve patient outcomes.