Dr. Hill on Resistance to BTK Inhibition in CLL

Brian T. Hill, MD, PhD, assistant professor, Hematology and Oncology, Cleveland Clinic, discusses resistance to BTK inhibition in chronic lymphocytic leukemia (CLL).

The main cause of resistance to BTK inhibition stems from mutations in BTK itself or other signaling pathways, says Hill. There are, however, assays and methods of discerning whether a patient harbors those mutations, he adds. If a patient harbors one of those mutations, they are likely to relapse quickly and become resistant to ibrutinib (Imbruvica) therapy. There are some noncovalent BTK inhibitors in development, although the current recommended approach following resistance is venetoclax (Venclexta).

Venetoclax is an incredibly active and well tolerated therapy, says Hill. Venetoclax has shown deeper remissions than what has been observed with either ibrutinib or acalabrutinib (Calquence). Moreover, venetoclax seems to show synergy with monoclonal antibodies, such as anti-CD20. Unlike with BTK inhibitors, venetoclax may be able to be discontinued after 2 years if a patient achieves a complete remission.