Dr. Ghosh on Differences Among Available BTK Inhibitors in B-Cell Malignancies

Nilanjan Ghosh, MD, PhD, director of the Lymphoma Program and a physician with Levine Cancer Institute, compares different BTK inhibitors in B-cell malignancies.

The available BTK inhibitors, ibrutinib (Imbruvica), acalabrutinib (Calquence), and zanubrutinib (Brukinsa), share some similarities but also differ from one another, says Ghosh. First, all 3 agents bind covalently at the C481 site of BTK, allowing for inhibition. Based on previous data, it appears that acalabrutinib and zanubrutinib are more selective for BTK compared with ibrutinib, adds Ghosh; however, this can translate into differing safety profiles.

In chronic lymphocytic leukemia, small lymphocytic lymphoma, or mantle cell lymphoma, head-to-head comparisons between these BTK inhibitors have not been made, so it is difficult to compare individual studies and their adverse effects (AEs), says Ghosh. Data are available with regard to zanubrutinib versus ibrutinib in Waldenström macroglobulinemia; however, no data are available with these agents against each other in other diseases. In general, it does appear that the rate of atrial fibrillation and some of the cardiovascular AEs could be higher with ibrutinib compared with the next-generation BTK inhibitors, says Ghosh. That may be related to the selectivity for BTK, concludes Ghosh.