Three-year cardiovascular and non-cardiovascular adverse events in patients with chronic lymphocytic leukemia or small cell lymphocytic lymphoma treated with Bruton tyrosine kinase inhibitors acalabrutinib or ibrutinib: a real-world analysis

Abstract Background Bruton tyrosine kinase (BTK) inhibitors play an important role in targeted treatment of B-cell lymphoproliferative disorders. However, adverse events may limit the proper course of treatment in many patients. The purpose of this study is to compare the risk of cardiovascular and non-cardiovascular adverse events in patients with chronic lymphocytic leukemia (CLL) or small cell lymphocytic lymphoma (SLL) treated with the first-generation BTK inhibitor ibrutinib versus second-generation acalabrutinib, using real-world data from a collaborative multinational network. Methods We used data from the network (TriNetX), which encompasses more than 100 healthcare organizations worldwide. We queried the database for patients aged ≥ 18 years with chronic lymphocytic leukemia or small-cell lymphomas treated with ibrutinib or acalabrutinib in the past 10 years before the analysis. We used propensity score matching to balance the cohorts. The 3-year cumulative incidences and hazard ratios for the following outcomes were calculated: atrial flutter or fibrillation, other arrhythmias, heart failure, ischemic stroke or peripheral embolism, acute coronary syndrome, bleeding, and sepsis. Results We compared 2,107 patients in each group. The 3-year incidences of atrial fibrillation or flutter in the acalabrutinib and ibrutinib groups were 7.11% and 14.78%, respectively, with a lower ratio in patients treated with acalabrutinib than in those treated with ibrutinib (hazard ratio, HR 0.68, 95% CI 0.55–0.84). New-onset hypertension occurred during 3-year follow-up in 16.29% of patients in the acalabrutinib group versus 27.8% in the ibrutinib group (HR 0,81, 95% CI 0.66–0.98). The incidence of sepsis was 6.49% in patients treated with acalabrutinib versus 11.37% of those treated with the ibrutinib group (HR 0.77, 95% CI 0.60–0.98). The two groups had no significant differences concerning the other adverse events. Conclusions In a large retrospective cohort using real-world data from electronic medical registers, patients with CLL or SLL treated with acalabrutinib had a better cardiovascular and non-cardiovascular safety profile than those treated with ibrutinib, with lower risks of atrial flutter or fibrillation, new-onset arterial hypertension, and sepsis.