Why Infection Rates Are Similar Across BTK Inhibitors

Danielle M. Brander, MD, of Duke University School of Medicine, compares infection rates across covalent Bruton tyrosine kinase (BTK) inhibitors in chronic lymphocytic leukemia (CLL). In two relapsed/refractory head-to-head trials, ELEVATE-RR (acalabrutinib vs ibrutinib in patients with del(17p) or del(11q)) and ALPINE (zanubrutinib vs ibrutinib), grade 3 or higher or serious infections occurred in roughly 3 in 10 patients in both arms. She asks why infection rates are similar despite differences in kinase selectivity. Marc J. Braunstein, MD, PhD, of NYU Grossman Long Island School of Medicine, explains that although second-generation agents are more specific for BTK, all act on the same B-cell receptor pathway and reduce function of the healthy B-cell compartment, lowering humoral immunity much like anti-CD20 antibodies; their advantages lie elsewhere, such as atrial fibrillation. Dr Brander adds that recommended vaccines should not be withheld from patients on long-term BTK inhibitors, since some still mount protective responses.