Major hemorrhage in chronic lymphocytic leukemia patients in the US Veterans Health Administration system in the pre‐ibrutinib era: Incidence and risk factors

Chronic lymphocytic leukemia (CLL) patients are at increased risk for major hemorrhage (MH). We examined incidence of and risk factors for MH in CLL patients before introduction of newer CLL therapies such as ibrutinib, which includes bleeding risk. This study included 24 198 CLL patients treated in the VA system before FDA approval of ibrutinib as CLL therapy. Data came from VA databases from 1999 to 2013. MH incidence was 1.9/100 person‐years (95% CI: 1.8‐1.9), with cumulative incidences of 2.3%, 5.2%, and 7.3% by year 1, 3, and 5, respectively. Median time from CLL diagnosis to MH was 2.8 years (range: 0‐15.7 years). In multivariate analyses, concurrent anticoagulant and antiplatelet use (HR: 4.2; 95% CI: 3.2‐5.6), anticoagulant use only (HR: 2.6; 95% CI: 2.3‐3.1), and antiplatelet use only (HR: 1.5; 95% CI: 1.3‐1.7) increased MH risk vs not receiving those medications; being nonwhite, male, having MH history, renal impairment, anemia, thrombocytopenia, and alcohol abuse were associated with increased MH risk. These pre‐ibrutinib data are important for providing context for interpreting MH risk in ibrutinib‐treated patients. As ibrutinib clinical use is increasing, updated analyses of MH risk among ibrutinib‐treated VA patients with CLL may provide additional useful insight.