Risk of New-Onset or Worsening Hypertension in Patients With Newly Diagnosed Chronic Lymphocytic
Leukemia Treated With BTK Inhibitors: A Real-World Study Using the Symphony Health Solutions Database

P1847

Tzuyung Douglas Kou,1 Lili Zhou,1 Jinzhi Zhou,1 Aileen Cohen,1 Wassim Aldairy,1 William B. White2
BeiGene USA, Inc, San Mateo, CA, USA; 2Cardiology Center, University of Connecticut Health Center, Canton, CT, USA

1INTRODUCTION

Table 1. Demographic and Baseline Characteristics at Treatment Initiation
BTK Inhibitor Cohort(n=2,392)

Non–BTK Inhibitor Cohort(n=28,167)

72.5

72.0

Male sex, n (%)

1,457 (61)14,812 (53)

CCI, mean (SD) [median]

3.0 (2.5) [3]2.7 (2.5) [2]• Bruton tyrosine kinase (BTK) inhibitors are an important therapeutic option for CLL1
• Concerns have arisen about the potential association between BTK inhibitors andthe risk of cardiovascular AEs2

Age, median, years• Hypertension has been associated with increased major cardiovascularAEs, including arrhythmia, myocardial infarction, stroke, heart failure, andcardiovascular death3• This study aims to describe the risk of new-onset and worsening hypertension inpatients with CLL treated with and without BTK inhibitors

METHODS
Data Source

Baseline hypertension, n (%)

BTK inhibitor cohort, n (%)
01
Drug classes after index dateb• New-onset hypertension was defined by antihypertensive medication use in theantihypertensive medications in the year following the index date, or a ≥2 foldincrease in antihypertensive drug dose with ≥2 prescriptions compared withbaseline daily dose in patients with pre-existing hypertension• Cox regression was used to compare the risk of developing new-onset or

Drug classes after index dateworsening hypertension between cohorts• Multivariable regression models, 1:1 propensity score matching, and inverse

medication at baselineaOverall Patients

2 (n=550)

686 (79)

71 (14)43 (8)

111

979

259

2537

370

3516

(17)

(12)

(15)

(13)

(15)

(12)

1.58

1.10

1.36

1.14

1.42

1.13

(1.31-1.90)(1.03-1.17)(1.21-1.54)(1.10-1.19)(1.29-1.58)(1.09-1.17)

124 (14)320 (62)

Patients, n (%)a80 (15)243 (5)102 (20)320 (58)≥3

19 (2)

27 (5)107 (20)

Non–BTK inhibitor cohort, n (%)

Patients With
Baseline
Hypertension

1 (n=520)a

Event rate per
100 person-months(95% CI), %0 (n=10,253)

1 (n=6,626)

2 (n=6,133)08,550 (83)890 (13)305 (5)

1

1,187 (12)4,576 (69)733 (12)

Unadjusted

372 (4)888 (13)

4,223 (69)≥3

144 (1)272 (4)872 (14)Model 1: age, sex,
race/ethnicity
Model 2: age, sex,
race/ethnicity, CCI
grouping, index yr

Drug classes used 1 year prior to index date. b Drug classes used within 1 year after index date.

• Patients in the BTK inhibitor cohort had a higher rate of new-onset or worsening

hypertension within 1 year of treatment initiation vs the non–BTK inhibitor cohort(Table 3) (IPTW HR, 1.28; 95% CI, 1.23-1.33)• Among patients without baseline hypertension, the rate of new-onset
hypertension was greater in the BTK inhibitor cohort vs the non–BTK inhibitor
cohort (IPTW HR, 1.50; 95% CI, 1.39-1.62)• The rate of worsening hypertension in patients with baseline hypertension wasgreater in the BTK inhibitor cohort than in the non–BTK inhibitor cohort(IPTW HR, 1.16; 95% CI, 1.11-1.23)

1.44(1.18-1.75)

Ref

1.19
(1.05-1.35)

Ref

1.25
(1.13-1.40)

Ref

Multivariable regressionb2

Non–BTK
BTK
Non–BTK
BTK
Non–BTKInhibitor Inhibitor Inhibitor Inhibitor Inhibitor(n=8,001) (n=1,748) (n=20,166) (n=2,392) (n=28,167)

Cox proportional hazards regressions, HR (95% CI)

Drug classes at baselinea• Worsening hypertension was defined by an increase in the number of concomitant• Approximately 64% of patients in both cohorts had received ≥1 antihypertensive

Patients WithoutBaseline
Hypertension

0 (n=872)

year following the index date in patients without pre-existing hypertension

medication or a medical encounter for hypertension, was 73% in the BTK inhibitor
cohort and 72% in the non–BTK inhibitor cohort

Table 3. New-Onset or Worsening Hypertension Within 1 Year After Index DateBTKInhibitor(n=644)

Drug classes at baseline

hypertension within 1 year after the index date in BTK inhibitor and non–BTK
inhibitor cohorts• Baseline prevalence of hypertension, defined as use of antihypertensive

important consideration in the long-term management of patientswith CLL undergoing treatment with BTK inhibitors

Table 2. Antihypertensive Medication Use Patterns• The primary analysis assessed the event rate of new-onset or worsening

cohort, n=2,392; non–BTK inhibitor cohort, n=28,167) (Table 1)• These data suggest that development of hypertension is an(19.5%-24.8%) increased their number of antihypertensive drug classes vs patientsin the non–BTK inhibitor cohort (14.2%-17.5%) (Table 2)

Study Assessments• A total of 30,559 patients with CLL were included in the analysis (BTK inhibitor

patients who initiated BTK inhibitors during the index period than inthose on non–BTK inhibitor treatments

20,166 (72)

• Within 1 year after the index date, more patients in the BTK inhibitor cohort(BTK inhibitor cohort) or were first diagnosed (non–BTK inhibitor cohort) between
January 1, 2019, and December 31, 2022, were included

RESULTSburden, and use of antihypertensive medication was common• The risk of new-onset or worsening hypertension was higher in

Determined based on use of antihypertensive medication or medical encounter for hypertension in the 3 years prior to treatment.
CCI, Charlson Comorbidity Index; SD, standard deviation.

• Patients with newly diagnosed CLL who initiated BTK inhibitor treatment

probability treatment weighting (IPTW) were used to account for differences inpatient characteristics between groups• In this real-world analysis, patients with CLL had a high comorbiditya• This retrospective cohort study used the Symphony Health Solutions Database,which contains deidentified and tokenized information that allows linkage ofpatient-level data from varied sources, such as hospital claims, physician offices,and prescription data, with record dates as recent as one month prior

1,748 (73)aCONCLUSIONSIPTW based on
propensity score1.38(1.14-1.69)
1.37(1.12-1.67)
1.50(1.39-1.62)

Ref

Ref

Ref

1.20
(1.05-1.36)
1.17(1.03-1.33)
1.16(1.11-1.23)

Ref

Ref

Ref

1.25
(1.12-1.39)
1.23(1.1-1.37)
1.28(1.23-1.33)

Ref

Ref

Ref

New cases of hypertension in patients without existing hypertension, and cases of worsening hypertension in patients with existing hypertension.
CCI, Charlson Comorbidity Index; IPTW, inverse probability treatment weighting; Ref, reference group.
aREFERENCES

1. Mato AR, et al. Clin Cancer Res. 2022;28(4):603.
2. Quartermaine C, et al. JACC CardioOncol. 2023;5(5):570.
3. Estupiñán HY, et al. Front Cell Dev Biol. 2021;9:630942.

DISCLOSURES

TDK, LZ, JZ, WA: Employment and may hold stock: BeiGene. AC: Consultant: BeiGene;
Equity holder: BeiGene. WBW: Consultant: BeiGene.

ACKNOWLEDGMENTS

The authors thank the patients and their families, investigators, co-investigators, and the study teams at each of the participating centers. This study was supported by BeiGene Ltd.
Medical writing support was provided by Shanen Perumal, PhD, of Nucleus Global, an Inizio company, and supported by BeiGene.

Presented at the EHA2024 Hybrid Congress; June 13-16, 2024; Madrid, Spain