Risk of hypertension in patients with CLL/SLL who participated in ALPINE: a post hocanalysis
Dulce Ramirez,1 Lipeng Chen,2 Jun Zhang,1 Wassim Aldairy,1 William B. White3
BeiGene USA, Inc, San Mateo, CA, USA 2BeiGene, Ltd, Beijing, China; 3Cardiology Center,
University of Connecticut Health Center, Canton, CT, USA
1Background: Bruton tyrosine kinase (BTK) inhibitors are an important therapeutic option forpatients with CLL/SLL. The first-generation BTK inhibitor, ibrutinib, is associated with anincreased risk of hypertension. Zanubrutinib is a next-generation BTK inhibitor designed tomaximize BTK occupancy and minimize toxicity with fewer off-target effects.
Aims: Evaluate the risk of developing hypertension based on initiation of antihypertensives(anti-HTN) in a post hoc analysis of ALPINE (NCT03734016).
Methods: Anti-HTN use in the zanubrutinib (n=324) and ibrutinib (n=324) treatment arms
was assessed. The definition of anti-HTN was based on Standardized Drug Grouping;concomitant anti-HTN were adjudicated by an independent hypertension specialist blinded to
BTK inhibitor assignment. Time to initiating new anti-HTN and time to adding a new class ofanti-HTN were assessed using the Kaplan-Meier method. Comparisons of time-to-onset
endpoints were analyzed based on the log-rank test.
Results: At baseline, patient characteristics were generally balanced between thezanubrutinib and ibrutinib arms (median age, 66.7 vs 67.1 years; male, 65.1% vs 71.4%;
history of hypertension, 50.9% vs 50.0%; type 2 diabetes mellitus, 10.1% vs 8.9%). Among
patients not on anti-HTN at baseline, 20.7% (n=35/169) of zanubrutinib- and 28.7%(n=51/178) of ibrutinib-treated patients initiated anti-HTN during the study. Among allpatients, fewer patients in the zanubrutinib arm initiated new anti-HTN (28.4% [n=92/324] vs32.4% [n=105/324]) and the anti-HTN were initiated later (hazard ratio [HR], 0.77; Pvalue=.071). Additionally, statistically fewer patients in the zanubrutinib arm compared with
the ibrutinib arm started anti-HTN in a new class (24.1% [n=78/324] vs 29.3% [n=95/324])
and the anti-HTN were started later (HR, 0.72; P-value=.034). The event rates for initiation ofnew anti-HTN or a new class of anti-HTN were consistently lower in the zanubrutinib vsibrutinib arm at each timepoint (Table).
Summary/Conclusion: In ALPINE, initiation of new anti-HTN or a new class of anti-HTN
occurred less frequently in the zanubrutinib arm vs the ibrutinib arm in patients with CLL/SLL.
Adoption of anti-HTN occurred sooner with ibrutinib than zanubrutinib. These findings should
be considered when initiating BTK inhibitor therapy in patients with CLL/SLL who have an
elevated cardiovascular risk.

EHA 2024

Initiation of new anti-HTN
Zanubrutinib

Ibrutinib

Initiation of new class of anti-HTN
Zanubrutinib

Ibrutinib

3 mo

No.
at
risk
289

Cumulative
eventrate, %
8.4

No.
at
risk
271

Cumulative
eventrate, %11.0

No.
at
risk
295

Cumulative
eventrate, %
6.5

No.
at
risk
277

Cumulative
eventrate, %
9.1

6 mo

268

12.9

238

19.0

276

10.4

246

16.4

12 mo

238

19.5

208

24.625214.7

216

22.0

18 mo

214

23.7

169

30.7

225

19.5

179

27.0

24 mo

149

28.0

115

33.8

157

23.5

127

29.2

30 mo

106

29.2

76

36.5

109

25.4

84

33.0

Presented previously at the ASH Annual Meeting; Dec 2023.

EHA 2024