Cardiovascular events reported in patients with B-cell malignancies treated with zanubrutinib

Author(s): Javid J. Moslehi1; Richard R. Furman2; Constantine S. Tam3; Joe-Elie Salem4; Christopher R. Flowers5; Aileen Cohen6; Meng Zhang6; Jun Zhang6; Lipeng Chen7; Han Ma6; Jennifer R. Brown8
Source: Blood Adv (2024) 8 (10): 2478–2490.
Original Article
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Dr. Anjan Patel's Thoughts

Pooled data across 10 studies of Zanubritinib show that tolerability is better with Zanubritinib compared to Ibrutinib. There is little reason to use ibrutinib in newly diagnosed patients in my opinion.

ABSTRACT

First-generation Bruton tyrosine kinase (BTK) inhibitor, ibrutinib, has been associated with an increased risk of cardiovascular toxicities. Zanubrutinib is a more selective, next-generation BTK inhibitor. In this analysis, incidence rates of atrial fibrillation, symptomatic (grade ≥2) ventricular arrhythmia, and hypertension were evaluated in a pooled analysis of 10 clinical studies with zanubrutinib monotherapy in patients (N = 1550) with B-cell malignancies and a pooled analysis of head-to-head studies comparing zanubrutinib with ibrutinib (ASPEN cohort 1; ALPINE). Among the 10 studies, most patients (median age, 67 years) were male (66.3%) and had CLL/SLL (60.5%). Overall incidence and exposure-adjusted incidence rates (EAIR) for atrial fibrillation, symptomatic ventricular arrhythmia, and hypertension were lower with zanubrutinib than ibrutinib. Despite a similar prevalence of preexisting cardiovascular events in ASPEN and ALPINE, atrial fibrillation/flutter incidence rates (6.1% vs 15.6%) and EAIR (0.2 vs 0.64 persons per 100 person-months; P < .0001) were lower with zanubrutinib than with ibrutinib. Symptomatic ventricular arrhythmia incidence was low for both zanubrutinib (0.7%) and ibrutinib (1.7%) with numerically lower EAIR (0.02 vs 0.06 persons per 100 person-months, respectively) for zanubrutinib. The hypertension EAIR was lower with zanubrutinib than ibrutinib in ASPEN but similar between treatment arms in ALPINE. The higher hypertension EAIR in ALPINE was inconsistent with other zanubrutinib studies. However, fewer discontinuations (1 vs 14) and deaths (0 vs 6) due to cardiac disorders occurred with zanubrutinib versus ibrutinib in ALPINE. These data support zanubrutinib as a treatment option with improved cardiovascular tolerability compared with ibrutinib for patients with B-cell malignancies in need of BTK inhibitors. These trials were registered at www.ClinicalTrials.gov as # NCT03053440, NCT03336333, NCT03734016, NCT04170283, NCT03206918, NCT03206970, NCT03332173, NCT03846427, NCT02343120, and NCT03189524.

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Author Affiliations

1Section of Cardio-Oncology & Immunology, UCSF School of Medicine, San Francisco, CA; 2Department of Medicine, Weill Cornell Medicine, New York, NY; 3Alfred Hospital and Monash University, Melbourne, VIC, Australia; 4AP-HP Sorbonne, Paris, France; 5Department of Lymphoma/Myeloma, The University of Texas MD Anderson Cancer Center, Houston, TX; 6BeiGene Inc, San Mateo, CA; 7BeiGene Co, Ltd, Beijing, China; 8Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA

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