Risk of new-onset hypertension in newly diagnosed chronic lymphocytic leukemia patientstreated with Bruton tyrosine kinase inhibitors: a real-world study using the Symphony HealthSolutions database
Tzuyung Douglas Kou,1 Lili Zhou,1 Jinzhi Zhou,1 Aileen Cohen,1 Wassim Aldairy,1 William B White2
1BeiGene USA, Inc, San Mateo, CA; 2Cardiology Center, University of Connecticut Health Center,Canton, CT

Background: Bruton tyrosine kinase inhibitors (BTKis) provide an important therapeutic option forpatients diagnosed with chronic lymphocytic leukemia (CLL). Concerns have arisen about a potential
association with the risk of cardiovascular events with BTKis.
Aims: Using the Symphony Health Solutions database, this study aims to describe the risk of newonset hypertension in CLL patients treated with and without BTKis.
Methods: Newly diagnosed CLL patients who started ibrutinib or acalabrutinib and those not treatedwith an approved BTKi between 2019 and 2022 were included in the analysis. The prevalence ofhypertension prior to and risk of new-onset hypertension after treatment initiation were defined by useof antihypertensive medication. Patient demographics and comorbidities were described. Multivariate
regression and inverse probability treatment weight based on propensity score were used to accountfor bias due to differences in patient characteristics between groups. Risk of hypertension up to 1 year
after index date was estimated. Hazard ratio and multivariate Cox-regression models were used todescribe the risk between groups.
Results: In CLL patients treated with (n=7,114) and without BTKis (n=34,571), demographics andclinical characteristics included age at the index date (mean: 70.2 years, BTKi; 69.0 years, withoutBTKi), sex (male: 59.8%, BTKi; 55.7%, without BTKi), and Charlson comorbidity scores (mean: 3.3,BTKi; 3.1, without BTKi). At baseline, the prevalence of hypertension defined by the use ofantihypertensive medication was 67.8% with BTKi and 67.6% without BTKi. Among patients without
any antihypertensive medication use at baseline, the rate of new-onset hypertension within 1 year
after treatment initiation was greater in patients with BTKis than without BTKis (Table).
Summary/Conclusion: In this real-world analysis, CLL patients treated with BTKis had a higher
burden of comorbidities, and use of antihypertensive medication was common. The risk of new-onset
hypertension was higher in patients initiated on BTKis than those on non-BTKi treatments. These datasuggest that development of hypertension is an important consideration in the long-term managementof CLL patients undergoing BTKi treatment.
In Patients Without Prior Medical Encounter or Medication Use forHypertension
Hypertension defined by any antihypertensive medication use
New onset of hypertension, n (%)
Event rate of hypertension (per 100 patient-months) (95% CI)
Absolute risk difference
Number needed to treat

BTKi(n=2,172)

Non-BTKi(n=10,626)

Hazard Ratio(95% CI)

Unadjusted
375 (17.2)
1,322 (12.4)
1.45 (1.30-1.63)
1.60 (1.40-1.80) 1.12 (1.06-1.18)
0.048 or 4.8%
Reference
21

Post hoc power calculation>80%

Multivariate regression models, adjusted hazard ratio (95% CI)
Model 1: Age and sex

1.40 (1.25-1.57)

Model 2: Age and sex, Charlson comorbidity score grouping (0, 1, 2, 3, 4+), index year

1.37 (1.22-1.54)

Model 3: Age and sex, individual Charlson comorbidity category, year of treatment initiation ordiagnosis

1.39 (1.24-1.56)

Inverse probability treatment weight based on propensity score, hazard ratio (95% CI)

1.44 (1.29-1.61)

EHA 2024