Real-World Data Support Zanubrutinib Use in Older Patients With CLL: Margaret Krackeler, MD

Margaret Krackeler, MD, of Kaiser Permanente in Northern California, discussed real-world findings from a study evaluating zanubrutinib treatment patterns and outcomes in patients with chronic lymphocytic leukemia (CLL), with particular focus on tolerability, cardiac safety, and outcomes in higher-risk populations. The study, published in Cancer Medicine, adds to a growing body of evidence suggesting that second-generation Bruton tyrosine kinase (BTK) inhibitors may offer important safety advantages over earlier agents while maintaining clinical effectiveness.

Krackeler explained that although overall adverse event (AE) rates with zanubrutinib were similar to those seen with other BTK inhibitors, the drug was associated with fewer treatment-limiting toxicities and lower rates of cardiac events—an especially meaningful finding for older patients and those with preexisting cardiovascular risk. In the cohort, approximately one-quarter of patients had baseline cardiac comorbidities, and nearly 40% were receiving anticoagulation or antiplatelet therapy prior to starting BTK inhibitor treatment. Despite this elevated risk profile, patients demonstrated strong tolerability and relatively low rates of cardiac AEs.

“This is especially relevant because we want to ensure that they are able to tolerate the medication long term so that they continue to have good disease control, even as their risk increases with age and additionally with cardiac comorbidities,” Krackeler said.

The study also offered encouraging signals among patients considered higher risk, with most remaining on zanubrutinib at the end of follow-up. However, Krackeler noted that the cohort was small, and cytogenetic data—critical for fully assessing risk—were incomplete for many patients, reflecting a common limitation of real-world studies.

While emerging evidence supports BTK inhibitor use in high-risk populations, she stressed that larger studies with more comprehensive molecular data are needed to better define outcomes in this group. Together, the findings underscore both the promise of zanubrutinib in routine practice and the ongoing need for robust real-world research to guide individualized CLL treatment decisions.

Reference

Krackeler ML, Chee BH, Orchanian AK, et al. Real-world treatment patterns and outcomes of zanubrutinib in chronic lymphocytic leukemia and small lymphocytic leukemia (CLL/SLL). Cancer Med. Published online October 25, 2025. doi:10.1002/cam4.71300