Bruton tyrosine kinase (BTK) is a key component of the B-cell receptor pathway and is a validated target for the treatment of chronic lymphocytic leukaemia (CLL). Ibrutinib is a covalent, small molecule BTK inhibitor approved for treatment of CLL. We analysed treatment patterns, outcomes, and adverse events (AEs) in patients with CLL treated with ibrutinib in a real-world setting. A retrospective chart review was conducted in patients with CLL who were treated with ibrutinib in UK oncology centers. Center selection was non-random, but all geographic regions were represented. Patients were eligible if they initiated ibrutinib after diagnosis of CLL, between January 2017 and June 2018, with at least 12 months of follow-up data available. Patients who died <12 months after ibrutinib initiation were also eligible. Haematology/oncology physicians reviewed selected medical records for eligibility and completed web-based data collection forms. Baseline medical history and data on treatment characteristics and AEs were collected. All analyses were descriptive. Thirty-four physicians contributed data for 259 ibrutinib-treated patients. In these patients, median follow-up was 16.7 months from ibrutinib initiation (index date) and 62.0 months from initial CLL diagnosis; median age was 71 years at ibrutinib initiation, 56% were male, 22.0% had del(17p) deletions, 21.6% had TP53 mutations, and hypertension was the most prevalent comorbidity (43.2%). First-line ibrutinib was initiated in 52 patients (20.1%) while 151 (58.3%) and 48 patients (18.5%) initiated ibrutinib as second- or third-line therapy, respectively. Median time to ibrutinib initiation was 43.7 months from CLL diagnosis and 84.6% of patients were still using ibrutinib at end of follow-up. Other therapies received included the combination of fludarabine, cyclophosphamide, and rituximab (first-line, 24.3%), bendamustine plus rituximab (first-line, 20.9%; second-line, 13.5%), and chlorambucil plus rituximab (first-line, 8.5%). Overall, the median progression-free survival was 28.7 months and median overall survival was not reached. The most common AEs observed during ibrutinib therapy were bruising (19.3%), cytopenias (17.0%), diarrhea (13.9%), and arthralgia (11.6%). Forty patients (15.4%) discontinued ibrutinib, mainly due to progressive disease (42.5%) or toxicity (22.5%); the median crude time to discontinuation was 10.1 months. The overall median crude time to dose reduction was 4.2 months (0.8─22.2 months) in 37 (14%) patients and was similar regardless of when ibrutinib was initiated. Toxicity was the most common reason (81.1%) for dose reduction. Among patients who initiated further therapy following discontinuation of firstor second-line ibrutinib (n=13), venetoclax was the most common therapy (53.8%). This analysis describes patient characteristics, outcomes and treatment patterns in ibrutinib-treated patients in the UK. The majority of ibrutinib use was in the second-line or later. AEs such as bruising and cytopenias were commonly reported in patients treated with ibrutinib.
