P105 | FIRST INTERIM ANALYSIS OF A REAL-WORLD ITALIAN NON-INTERVENTIONAL STUDY ASSESSING THE USE OF ACALABRUTINIB IN THE TREATMENT OF PATIENTS WITH CHRONIC LYMPHOCYTIC LEUKEMIA (CLL- ARISE STUDY NCT06205498)

Acalabrutinib (acala), a II generation BTKi, is reimbursed in Italy for the treatment of naïve or relapsed refractory CLL patients (pts) since Dec.2021. ARISE (NCT06205498) is an observational, longitudinal secondary data usage study based on a retrospective cohort of CLL pts, who started acala monotherapy between 1st May 2021 and 30th April 2022 (index date) according to Italian legislation dlg.219/2006 art.125. Real-world evidence (RWE) is a crucial complement to clinical trial data, offering valuable insights in post-marketing settings. ARISE aims to provide meaningful data on the use of acala in Italian clinical practice. As of 31st March 2024, a total of 151 eligible pts were enrolled across 42 Italian sites. Mean age (± SD) at index date was 69 (± 10.28) years and 58% pts (n=74) were male. Among pts with available data (n=127), del(17p) was reported in 8.7% (n=11), TP53 was mutated in 7.9% (n=10) and IGHV was unmutated in 48% (n=61) pts Median time from CLL diagnosis to acala initiation was 30 months, with 78.8% pts (n=119) in 1L treatment. ECOG PS at baseline was 0 or 1 in 76.4% pts (n=97). The most relevant pre-existing cardiovascular comorbidities at the index date were hypertension (52.8%, n=67), cardiac rhythm disorders (11%, n=14), atrial fibrillation (6.3%, n=8), atrial flutter (0.8%, n=1) and congestive heart failure (2.4%, n=3). With a median follow-up of 27 months, the median Time-to-Discontinuation (TTD), estimated by Kaplan-Meier method, was not reached. 10 pts (6.7%) permanently discontinued acala during the study, the most common reasons were adverse event (AE) (headache n=3, myocardial infarction n=2, not specified n=2) and physician’s choice (n=3). No discontinuations for Progression Disease (PD), compliance issue, or death were reported. Following acala initiation, 14.5% (n=18) pts underwent at least a dose change (DC), mostly due to AE(n=13) or physician’s choice (n=2), while treatment was temporarily interrupted at least once in 45.2% pts (n=56). Reported AE leading to a DC, treatment interruption or permanent discontinuation are reported in Table 1. These preliminary results align with previous safety and efficacy profiles from acala registration trials: a robust safety profile reduces the risk of AEs and enhances overall treatment effectiveness increasing patient benefit. Given the interim nature of the analysis, data availability may differ between variables. Further analysis will consolidate these findings at the end of the study.