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.
Keywords: chronic lymphocytic leukemia, first-line treatment, healthcare costs, ibrutinib, real-world evidence, targeted therapy