Dr. Tam on FDA Approved BTK Inhibitors in Hematologic Malignancies

Constantine S. Tam, MD, MBBS, associate professor, Peter MacCallum Cancer Centre, discusses the 3 FDA approved BTK inhibitors in hematologic malignancies: ibrutinib (Imbruvica), acalabrutinib (Calquence), and zanubrutinib (Brukinsa).

Ibrutinib, acalabrutinib, and zanubrutinib all target BTK in the same place and bond and disable BTK irreversibly, but the drugs differ in the specificity of targeting, explains Tam. Ibrutinib targets related enzymes including BTK, ITK, TAG, and EGFR, which may explain many of the adverse events (AEs) associated with ibrutinib, says Tam.

In comparison, acalabrutinib and zanubrutinib also do not solely target BTK. Comparatively across clinical trials, none of them head-to-head, it appears acalabrutinib and zanubrutinib are associated with reductions in select AEs, including bleeding, atrial fibrillation, myalgias, and arthralgias, suggesting that these targeted drugs may have more activity, according to Tam.

Another major difference between the 3 BTK inhibitors is drug penetration. With zanubrutinib, high drug levels are achieved with the current levels of dosing, which are around 6 to 10 times higher in drug exposure compared with acalabrutinib or ibrutinib, says Tam. The hope is higher drug levels will mean better clinical responses for patients, concludes Tam.