BTK inhibitors linked to increased risk for pericardial effusion

medwireNews: People receiving Bruton tyrosine kinase (BTK) inhibitors for the treatment of B-cell malignancies could be at increased risk for developing pericardial effusion, suggests a database analysis.

Noting that this represents “the first large-scale quantification of this association,” the researchers say that “cardiovascular vigilance and multidisciplinary collaboration remain essential during BTK [inhibitor] therapy.”

They drew on the TriNetX Network database to identify patients diagnosed with chronic lymphocytic leukemia, small B-cell lymphoma, mantle cell lymphoma, Waldenström macroglobulinemia, or follicular lymphoma between January 2014 and December 2024 who did (n=14,687) or did not (n=138,097) receive BTK inhibitors (ibrutinib, acalabrutinib, zanubrutinib, or pirtobrutinib).

After propensity score matching to balance demographics, comorbidities, and medications, 14,444 patients (mean age 74 years, 38% women) remained in each group.

Over a mean follow-up of 314 days, the investigators found that patients who took BTK inhibitors were more than twofold likely to experience pericardial effusion or tamponade than their counterparts who did not, at incidence rates of 0.9% and 0.4%, respectively, and a significant hazard ratio (HR) of 2.18.

“This association remained consistent in sensitivity analyses using 14- and 30-day landmark approaches,” with respective significant HRs of 2.19 and 2.09, report Ramzi Ibrahim (Mayo Clinic Arizona, Phoenix, USA) and co-authors in a research letter published in JAMA Oncology.

The team also found a significant increase in the risk for other cardiovascular events among BTK inhibitor users versus nonusers, including new-onset atrial fibrillation (HR=2.23), cardiac arrest (HR=1.91), ischemic stroke (HR=1.61), acute myocardial infarction (HR=1.42), and acute heart failure (HR=1.30).

By contrast, although the all-cause mortality rate was numerically higher in the BTK inhibitor group, at 9.4% versus 8.3% in the control group, the between-group difference was not statistically significant.

Ibrahim et al acknowledge several limitations of the study, such as “residual confounding, short follow-up duration, absence of dose- or duration-response data, and lack of imaging detail to characterize pericardial effusion severity.”

And they therefore highlight “the need for further prospective studies to validate.”

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JAMA Oncol 2026; doi:10.1001/jamaoncol.2025.6605