Hypertension in patients with chronic lymphocytic leukemia/small lymphocytic lymphoma in ALPINE: a secondary analysis

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) 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 160 mg twice-a-day or ibrutinib 420 mg 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. In all patients, time-to-initiation of a new antihypertensive class was longer with zanubrutinib vs ibrutinib; in those without baseline antihypertensive therapy, time-to-initiation of a new antihypertensive agent was also longer. 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.