Poster Session I: Chronic lymphocytic leukemia and related disorders - Clinical
The true prevalence of cardiovascular disease (CVD) in chronic lymphocytic leukemia (CLL) and its incidence after treatment with chemoimmunotherapy in an unselected CLL-population has not been previously described. In 2015 the Bruton's Tyrosine Kinase (BTK)-inhibitor ibrutinib was introduced in Sweden. Its use in CLL has increased rapidly due to data demonstrating high efficacy and tolerability. However, an increased risk of adverse events (AE) affecting the cardiovascular system, such as atrial fibrillation (AF) (4-17%) and hypertension (20%) have been reported after treatment with ibrutinib, with higher risk in patients with previous CVD. Due to this, real-world data on CVD in CLL are of clinical interest.
To investigate the prevalence of CVD, especially AF and hypertension, at the time of CLL diagnosis in an unselected, population-based CLL cohort. To investigate the prevalence of CVD at time of treatment initiation in CLL patients requiring therapy. To investigate the incidence of CVD within three and five years after start of first-line therapy with chemoimmunotherapy.
All Swedish patients diagnosed with CLL (ICD10: C91.1) between 2007-2010 (n = 2078) were identified from the Swedish Cancer register and the Swedish CLL register. Of these, 884 (43%) were in need of treatment, identified using data from the Swedish CLL register on patients starting first-line therapy 2007-2015. For all patients, data on CVD was collected using the International Classification of Diseases ((ICD)-10 codes I00-I99 and corresponding ICD-9 codes) from the nationwide patient register (registering all inpatient care from 1987 and specialist outpatient care from 2001 and onwards). The Swedish Cause of Death register was used to identify CVD as causes of death. This was done for: (i) all CVDs diagnosed within ten years prior to CLL diagnosis in all patients (ii) all CVDs diagnosed within ten years prior to treatment initiation in those in need of treatment (iii) all CVDs diagnosed within 3 and 5 years after start of primary treatment in patients without previous CVD.
The proportion of patients having had any CVD within 10 years prior to CLL diagnosis was 32.5% (n = 674/2075, Table 1). Out of these 674, 10.8% were diagnosed with AF and 22.0% with hypertension. The proportion of patients presenting with CVDs within 10 years prior to start of treatment with chemoimmunotherapy was 30.9% (n = 273/884). With a median follow-up of 4.8 years after treatment initiation, 18% developed a primary CVD within 3 years, and 21% within 5 years (table 1).
In this nation-wide population-based study, we found that 1/3 of all patients with CLL had a diagnosis of CVD within 10 years prior to diagnosis, with a similar proportion of prior CVD found in the cohort of patients in need of treatment. Furthermore, 1/5 of patients with no previous history of CVD, developed an event within 5 years after starting treatment with chemoimmunotherapy. The high proportion of patients with a history of CVD, especially AF and hypertension, at the time CLL-diagnosis, as well as the continuing increase of CVD over time after starting treatment, is of concern. In particular as treatment with BTK-inhibitors is associated with an increased risk of further cardiovascular events, especially in patients with pre-existing CVD.