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
Real-World Progression-Free Survival and Healthcare Resource Utilization Associated with Daratumumab Use in Transplant-Ineligible Multiple Myeloma Patients in Italy
Purpose: This study evaluated real-world clinical and economic outcomes associated with daratumumab-based regimens in patients with multiple myeloma (MM) ineligible for autologous stem cell transplantation (ASCT) in Italy. Differences in healthcare resource use according to daratumumab administration route (intravenous vs subcutaneous) were also explored.
Methods: A retrospective observational analysis was conducted using administrative healthcare databases from Italian Local Health Units covering ~12 million individuals (2018– 2023). Patients with MM receiving daratumumab in first-line (1L) or second-line (2L) therapy were included. Real-world progression-free survival (rwPFS), defined as time to treatment switch or death, was used as a proxy endpoint for disease progression, and healthcare resource utilization were compared between treatment regimens. Propensity score weighting was applied to to improve comparability between treatment groups. Direct healthcare costs captured in administrative databases were analyzed from the perspective of the Italian National Health System.
Results: Among 790 non-ASCT MM patients, 344 received 1L DaraRd and 413 received 2L DaraRd. In the 1L setting, median rwPFS was not reached for DaraRd and was 25.7 months for Rd (p=0.011). In 2L, median rwPFS was 42.9 months for DaraRd versus 19.1 months for Rd (p < 0.001). In 1L, DaraRd was associated with lower hospitalization costs compared with Rd for both all-cause (€ 4324 vs € 7971) and MM-related (€ 2862 vs € 6693) admissions. In 2L, differences in hospitalization costs were smaller and not statistically significant.
Conclusion: In this real-world analysis, daratumumab-based regimens were associated with longer rwPFS compared with Rd among transplant-ineligible MM patients, in both 1L and 2 L settings. In 1L treatment, these outcomes were accompanied by lower hospitalization costs. Given the retrospective design and the use of administrative healthcare data, these findings should be interpreted with caution, but they contribute to the growing body of real-world evidence on treatment outcomes and resource utilization in routine clinical practice.