First-Line Treatment of Chronic Lymphocytic Leukemia in Italy: Real-World Evidence on Utilization, Outcomes, and Healthcare Costs

Background: Chronic lymphocytic leukemia (CLL) is the most common adult leukemia in Western countries, mainly affecting older people. Targeted agents have reshaped first-line (1L) strategies, making real-world evidence important to complement clinical trials. Objective: To estimate the incidence of Italian patients initiating first-line CLL therapy (2019– 2022) and describe demographics/clinical profile, treatment patterns, adherence, outcomes (overall survival [OS], time to next treatment [TTNT]), and healthcare costs from the perspective of the Italian National Health System (NHS). Methods: A retrospective observational study using administrative healthcare databases (~9 million residents) was conducted on CLL patients starting 1L therapy (index-date) for CLL. Baseline characteristics were assessed in the 12 months pre-index; follow-up was ≥ 12 months. Drug use, adherence (medication possession ratio), dose adjustments, OS, TTNT, and direct costs were analyzed with descriptive and multivariable methods. Results: A total of 1479 patients initiated 1L therapy: 63.9% chemotherapy (CHT), 23.2% ibrutinib, 3.2% acalabrutinib, and 9.7% other regimens. CHT remained common, especially among older and more comorbid patients. Ibrutinib showed lower mortality versus CHT (HR 0.663; p=0.002) and longer TTNT (median not reached). Dose adjustments were frequent; extended refill intervals did not appear to reduce drug survival. Mean annual cost per patient was € 38,573, mainly driven by drug acquisition; ibrutinib users had lower hospitalization and outpatient costs than other 1L groups. Conclusion: In Italian practice, ibrutinib was the main targeted 1L option and was associated with improved survival and delayed progression versus CHT. Despite higher drug costs, reduced hospital-based resource use suggests favourable overall clinical and economic impact.