Dr. Shadman on Considerations for BTK inhibitors in CLL

Mazyar Shadman, MD, a physician and associate professor in the Divisions of Medical Oncology and Clinical Research at Seattle Cancer Care Alliance, discusses considerations for BTK inhibitors in the treatment of patients with chronic lymphocytic leukemia (CLL).

Ibrutinib (Imbruvica) is a first-generation BTK inhibitor that has the longest follow-up data in CLL, Shadman says. The agent has demonstrated efficacy in patients with this disease; however, it does have some notable adverse effects (AEs) that could lead to discontinuation, Shadman adds.

The second-generation BTK inhibitor acalabrutinib (Calquence) has also demonstrated efficacy in this population and the agent is FDA approved for use in the frontline and relapsed setting, Shadman notes. As the agent is more specific to BTK, it has lower rates of associated AEs, according to Shadman. In patients who have progressed on ibrutinib, switching to acalabrutinib is not an option, as their mechanisms of resistance are similar, Shadman says.

Data presented during the 2020 ASH Annual Meeting & Exposition suggest that zanubrutinib (Brukinsa), another second-generation BTK inhibitor, could be effective with acceptable tolerability patients with CLL who cannot tolerate other BTK inhibitors. Currently, however, zanubrutinib has only received regulatory approval in the United States for use in patients with mantle cell lymphoma, Shadman concludes.