Adverse Health Events in Chronic Myeloid Leukaemia Patients Treated With Tyrosine Kinase Inhibitors 2009–2019: A Real-World Study From the UK's Haematological Malignancy Research Network

Outcomes among patients with chronic myeloid leukaemia (CML) improved markedly when tyrosine kinase inhibitors (TKIs) were introduced into routine clinical practice around the turn of the century. Nonetheless, adverse events still occur, survival remains suboptimal and the long-term health impact of the disease and its treatment is poorly understood. Using data from an established UK population-based cohort of haematological malignancies, we compared the morbidity of 411 CML patients treated with TKIs 2009–2019 to that of individually age- and sex-matched general population-based controls (n = 4099). Over the course of follow-up (to March 2021, median 5.3, interquartile range 3.0–8.2 years), patients were more likely than controls to die from cardiovascular or respiratory diseases; Hazard Ratios of 1.9, 95% Confidence Interval, 95% CI = 1.2–2.8 and 2.4, 95% CI 1.2–4.9 respectively. Hospital admissions for cardiovascular or respiratory conditions were similarly elevated; HR = 1.6, 95% CI 1.3–1.9; HR = 2.3, 95% CI 1.6–3.4 respectively. The risk of a cardiovascular admission varied over time; being increased in the first year (HR = 2.4, 95% CI 1.5–3.8), and then again 5 years or more after starting TKI therapy (HR = 2.3, 95% CI 1.5–3.6); no increase was evident in the intervening years (HR = 1.1, 95% CI 0.8–1.7). While not related to excess mortality, admissions for infections and gastrointestinal conditions occurred more frequently among cases than controls; the increased risk remaining largely constant over the course of follow-up. In the era of TKIs, these real-world analyses revealed that CML patients are at increased risk of severe cardiovascular events several years after starting treatment, and that admission for infections and gastrointestinal conditions are raised throughout.