Baseline Characteristics from Arise Study, an Italian Non-Interventional Study Assessing the Real-World Use of Acalabrutinib in the Treatment of Patients with Chronic Lymphocytic Leukemia (CLL)
Authors: Mauro Francesca Romana , Visentin Andrea , Laurenti Luca , Gallo Susanna , Pavone Vincenzo , Nicoli Paolo , Postorino Massimiliano , Scortechini Ilaria , Scarfo Lydia , Foglietta Myriam , Borella Chiara , Palumbo Gaetano , Di Rienzo Nicola , Tani Monica , Tafuri Agostino , Sportoletti Paolo , Scalzulli Potito Rosario , Pennese Elsa , Pastore Domenico , Pasquini Cristina , Malandruccolo Luigi , Di Veroli Ambra , De Santis Gaetano , Catania Gioacchino , Tamburini Anna , Stelitano Caterina , Pane Fabrizio , Musto Pellegrino , Magagnoli Massimo , D'Arena Giovanni , Caracciolo Daniele , Bongiovanni Deborah , Reda Gianluigi , Padrone Claudia , Gentile Massimo 
Published: December 2024

Chronic lymphocytic leukemia (CLL) is the most prevalent form of leukemia in adults in the Western countries, with an annual incidence of approximately 5 cases per 100,000 inhabitants in Italy. Acalabrutinib, a selective second-generation Bruton Tyrosine Kinase (BTK) inhibitor, received EMA (European Medicines Agency) approval in 2020 for the treatment of CLL patients and AIFA (Agenzia Italiana del Farmaco) reimbursement as monotherapy in December 2021. However, further data are still required to evaluate the use of acalabrutinib in the real-world post-marketing authorization settings. ARISE is an Italian, observational, multicenter, longitudinal secondary data usage study based on a retrospective cohort of adult patients with a diagnosis of CLL, who have initiated acalabrutinib monotherapy between 1st May 2021 and 30th April 2022 (index date), regardless of the treatment status at the time of inclusion, according to Italian legislation dlg. 219/2006 art.125.
ARISE study (NCT06205498) started in August 2023 (First Patient In), and it will enroll about 190 pts in 45 Italian sites. The study will provide the first Italian real-world data on the use of acalabrutinib in CLL. Patients will be retrospectively observed up to 5 years since the last enrolled patient index date or until study withdrawal (consent withdrawal, physician's choice, loss to follow-up or death), whichever occurs first, regardless of acalabrutinib discontinuation.All visits and assessments are performed as per site clinical practice. Descriptive statistics were used to describe baseline characteristics.
As of June 2024, a total of 88 patients were identified and included in the analysis for demographic and baseline characteristics. Mean age (± SD) was 68.5 (± 10.4) years, and 49 patients (55.7%) were male. At the time of treatment initiation males were younger than females (67.1±11.4 years vs 70.3±8.8 years). In 68 (77.3%) patients acalabrutinib was the first treatment, in the other 20 patients (22.7%) was administrated as subsequent therapy. Median time (min-max) from diagnosis to index date was 3 years (0-23) and most patients (n=86, 98.9%) received an initial dose of 100mg/bid, as per the Summary of Product Characteristics (SmPC). At baseline, del(17p) was reported in 6/71 (6.8%), TP53 was mutated in 3/73 (3.4%) and IGHV was unmutated in 43/61 (48.9%) patients with available data. A full CLL specific FISH profile was available in 58 (65.9%) patients. Binet classification at diagnosis was as follows: 52.3% stage A, 36.4% stage B, 11.4% stage C, while at baseline the distribution shifted to 10.2%, 44.3% and 45.5%, respectively. At baseline, Eastern Cooperative Oncology Group performance status (ECOG PS) score was 0 or 1 in 69 patients (78.4%), Median (± IQR) Cumulative Illness Rating Scale for Geriatrics (CIRS-G) score was 6.0 (4.5). Relevant pre-existent cardiovascular comorbidities at the index date were hypertension (n=43, 48.9%), cardiac rhythm disorders (n=8, 9.1%), atrial fibrillation (n=4, 4.5%), atrial flutter (n=1, 1.1%) and congestive heart failure (n=1, 1.1%). Active hemolysis (autoimmune-related) was reported in 1 patient only (1.1%) at the time of treatment initiation.
In this preliminary report the demographic characteristics of 88 enrolled patients are consistent with those of general population with CLL. Moreover, disease biological features before starting acalabrutinib treatment were similar to previously reported cohorts for pts with CLL receiving therapy both in clinical trials and in other real-world settings. Further reports will be focused on acalabrutinib time to discontinuation, reasons of discontinuation (due to CLL or suspected ADR) and Time to Next Treatment.