Introduction: Patients with B cell malignancies have an inherent increased risk of bleeding. However, the incidence of major hemorrhage among patients with MCL and CLL has not been described. The objective of this study is to evaluate the risk of major hemorrhage in a real world setting by using a population-based data source.
Methods: The SEER-Medicare linked database, a database of SEER cancer registry data linked to individual Medicare administrative claims, was utilized to follow a cohort of persons newly treated for CLL or MCL to estimate the incidence of major hemorrhage (CNS and non-CNS). Major hemorrhage was defined as having at least one code for hemorrhage in a critical area or organ or having another bleeding code with a transfusion within 14 days of the event. Patients with a cancer diagnosis on or after 1/1/2000 were followed through disenrollment from the database, death, the occurrence of major hemorrhage, or the end of the study period (12/31/2011), whichever came first. Incidence rates (IR) of major hemorrhage were characterized in terms of incidence per person-years (pys) of follow-up with 95% confidence intervals calculated according to a Poisson distribution. Rates in the CLL and MCL populations were compared to those in the age and gender-matched general population of a sample of non-cancer Medicare patients using Cox proportional hazards models.
Results: A total of 1,587 treated MCL patients, 6,717 treated CLL/SLL patients, and 14,816 age and gender-matched non-cancer patients were identified in the database. Median age among all three cohorts was approximately 75 years. Among patients treated for MCL, 287 (18%) had at least one major hemorrhage, corresponding to an incidence of 5.8 per 100 pys. Among 6,717 CLL patients, 1,211 (18%) had at least one major hemorrhage (IR: 6.0 per 100 pys). In the age and gender-matched non-cancer population, incidence of major hemorrhage was 1.6 per 100 pys. The hazard ratio for development of any major hemorrhage among CLL patients compared to the non-cancer cohort was 8.3 (95% CI: 7.5-9.2), and for MCL compared to the non-cancer cohort was 8.8 (95% CI: 7.6-10.2). IR of CNS hemorrhage was also higher among MCL and CLL patients (0.9 and 1.2 per 100 pys, respectively) compared to the non-cancer cohort (0.04 per 100 pys). Gastrointestinal hemorrhage was the most frequent site of occurrence.
Conclusions: Among persons newly initiating treatment for CLL and MCL, incidence of major hemorrhage was found to be over 8 times higher than that of the age- and gender-matched general population. Additional analyses to establish whether this increased risk is attributable to the disease itself, comorbid conditions, choice of cancer therapy, or concomitant medications in the patient population and/or other risk factors are planned. Baseline risks among CLL and MCL patients should be considered when establishing risk/benefit profiles of a particular treatment.
Gifkins:Johnson and Johnson: Employment. Matcho:Johnson and Johnson: Employment. Yang:Pharmacyclics, Inc: Employment. Xu:Johnson and Johnson: Employment. Gooden:Pharmacyclics, Inc.: Employment. Wildgust:Janssen Pharmaceuticals, Inc.: Employment.
Asterisk with author names denotes non-ASH members.