https://orcid.org/0000-0003-3331-9491
KEY POINTS
In the ALPINE trial, unlike the ASPEN trial, hypertension rates were comparable for zanubrutinib vs ibrutinib
Initiation of antihypertensive therapy occurred later with zanubrutinib vs ibrutinib, providing context for the hypertension rates in ALPINE
ABSTRACT
Hypertension is a common side effect of Bruton tyrosine kinase inhibitors (BTKis). The second-generation BTKi zanubrutinib has high BTK selectivity, which may minimize off-target effects. A phase 3 trial (ALPINE; NCT03734016) demonstrated improved efficacy and safety of zanubrutinib vs ibrutinib in patients with relapsed/refractory (R/R) chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL). To better understand hypertension risk with zanubrutinib vs ibrutinib in ALPINE, this post hoc analysis evaluated hypertension development by measuring antihypertensive therapy initiation. Eligible adults with R/R CLL/SLL were randomized to zanubrutinib 160mg twice-a-day or ibrutinib 420mg daily until disease progression/unacceptable toxicity. Differences in treatment-emergent hypertension, antihypertensive therapy use, and changes in blood pressure were evaluated. Of 648 patients (zanubrutinib, n=324; ibrutinib, n=324), nearly half used antihypertensive therapy at baseline (zanubrutinib, 48%; ibrutinib, 45%). With zanubrutinib vs ibrutinib, initiation of a new antihypertensive agent (28% vs 32%) or new antihypertensive class (24% vs 29%) were comparable. In patients without baseline antihypertensive therapy, 21% vs 29% with zanubrutinib vs ibrutinib, respectively, initiated new antihypertensive therapy (P=.087). In all patients, time-to-initiation of a new antihypertensive class was longer with zanubrutinib vs ibrutinib (hazard ratio [HR]=0.72; P=.034); in those without baseline antihypertensive therapy, time-to-initiation of a new antihypertensive agent was also longer (HR=0.62; P=.029). Mean systolic blood pressure changes were lower with zanubrutinib vs ibrutinib. In conclusion, zanubrutinib was associated with longer time to initiation of antihypertensive therapy compared with ibrutinib in ALPINE. These findings could be of clinical importance when initiating BTKi therapy in patients with CLL/SLL. This trial was registered at www.ClinicalTrials.gov as NCT03734016.
Author notes
Co-first authors
Data Sharing Statement
On request, and subject to certain criteria, conditions, and exceptions, BeOne Medicines Ltd, will provide access to individual de-identified participant data from BeOne Medicines Ltd-sponsored global interventional clinical studies conducted (1) for indications that have been approved based on the BeOne Medicines Ltd data sharing policy or (2) in programs that have been terminated. BeOne Medicines Ltd shares data only when permitted by applicable data privacy and security laws and regulations, shares when it is feasible to do so without compromising the privacy of the study participants and other considerations. Data requests may be submitted to ClinicalTrials@BeOneMedicines.com.
