Real‐world treatment patterns, adverse events and clinical outcomes in patients with chronic lymphocytic leukaemia treated with ibrutinib in the UK

Abstract

Chronic lymphocytic leukaemia (CLL) is the most common leukaemia in adults in the UK. Ibrutinib, an oral Bruton tyrosine kinase inhibitor (BTKi) for CLL approved by the UK's National Institute for Health and Care Excellence in January 2017, represented a major shift in CLL management. Real-world data on ibrutinib use in routine clinical practice will inform patients' and physicians' decision-making. We conducted a retrospective medical chart review of UK patients with CLL who initiated ibrutinib between January 2017 and July 2018. Data for 259 patients were contributed by 34 haematology-oncology specialists, with a median follow-up duration of 16.7 months.Median age at ibrutinib initiation was 71 years. Ibrutinib first-line monotherapy was prescribed in 20.1% of patients. Ibrutinib was permanently discontinued in 15.4% of patients, mostly owing to progressive disease. Adverse events (AEs) were reported in 151 patients (58.3%). The most common were bruising (19.3% of patients), cytopenias (17.0%) and diarrhoea (11.6%). Ibrutinib dose reduction was observed in 14.3% of patients and was temporarily discontinued in 10.4% of patients, with the main reason for both being toxicity. These results expand the real-world evidence on ibrutinib therapy and demonstrate a high burden of AEs, highlighting the need for more tolerable BTKis.

Incidence of cardiovascular and bleeding events and reasons for discontinuation in patients with chronic lymphocytic leukemia treated with ibrutinib—A retrospective analysis on consecutive patients from a well‐defined region

“…In previously published real‐world studies with varying follow‐up times, the majority shorter than ours, the incidence ranged between 3% and 17%. In these studies, AF was reported as cumulative incidence at the end of follow up, and therefore a direct comparison with our data is not always possible 6,18,20,21,24–26 . Also, real‐world data from long‐term follow‐up are limited.…”

“…4,5 In real-world studies with a median follow-up shorter than 2 years, discontinuation rates have been reported to range from 15% to 42%. 6,[18][19][20] In one study conducted by Moldovianu et al, with a median follow-up time of 32 months (range 22-51), 44% of the patients discontinued treatment. 21 However, only 9% of the patients discontinued due to toxicity while in our study 25% did, which could be explained by the older age and higher comorbidity of the patients in our cohort.…”

“…Reasons for treatment discontinuation are also displayed. of AF at 1 year was 11.9% (95% CI[7][8][9][10][11][12][13][14][15][16][17][18], at 2 years 14.4% (95% CI 9-22), at 3 years 15.5% (CI 9.9-22), at 4 years 18.2% (95% CI 12-26) and at 5 years 22.7 (95% CI 15-31) as illustrated in Figure3.The median time to AF diagnosis from treatment start was 7 months (range 0.5-59) and median age at AF diagnosis was 77 years (range 44-89). Seventeen patients (63%) were diagnosed within the first year of treatment.…”

Real-World Clinical Outcomes and Adverse Events in Patients with Chronic Lymphocytic Leukemia Treated with Ibrutinib: A Single-Center Retrospective Study

“…Our findings are comparable with RCTs data. Contrastingly, real-world data either refute [ 11 , 12 , 15 , 20 , 37 ] or confirm [ 14 , 17 , 18 , 30 ] a good tolerance profile.…”

“…Far from being mutually exclusive, they are complementary and should be used in tandem to secure optimum management [ 10 ]. Compared to RCTs evidence, several real-world studies found lower survival and higher discontinuation rates with ibrutinib [ 11 , 12 , 13 , 14 , 15 , 16 ], while others reported similar results [ 17 , 18 , 19 , 20 ]. Furthermore, the real-life use of ibrutinib has sparked controversy on several other counts, including treatment adherence, adverse events (AEs), long-term outcomes, and high-risk factors [ 13 , 14 , 15 , 16 , 20 , 21 , 22 ].…”