Dr. Danilov on the Differences Between Covalent and Noncovalent BTK Inhibitors in MCL

Alexey V. Danilov, MD, PhD, associate director, Toni Stephenson Lymphoma Center, professor, Division of Lymphoma, Department of Hematology and Hematopoietic Cell Transplantation, City of Hope, discusses the key differences between covalent and noncovalent BTK inhibitors in mantle cell lymphoma (MCL).

The key difference between covalent and noncovalent BTK inhibitors is what each agent can target, Danilov says. Noncovalent BTK inhibitors target BTK mutations, which have been associated with resistance to covalent BTK inhibitors, such as ibrutinib (Imbruvica), zanubrutinib (Brukinsa), and acalabrutinib (Calquence), Danilov adds. Specifically, resistance to covalent BTK inhibitors stem from BTKC481S mutations and others in patients with MCL or chronic lymphocytic leukemia, Danilov explains.

Noncovalent BTK inhibitors are designed to inhibit specific BTK mutations, and these agents have demonstrated clinical activity in patients who have previously failed on covalent BTK inhibitors, Danilov concludes.