John M. Pagel, MD, PhD, chief of the Hematologic Malignancies Program, and director, Hematopoietic Cell Transplantation Program, at Swedish Cancer Institute, discusses ongoing research with BTK inhibitors in chronic lymphocytic leukemia (CLL).

Zanubrutinib (Brukinsa), which received an accelerated approval in November 2019 in mantle cell lymphoma, is also under investigation in CLL. The agent appears to be well tolerated with low rates of atrial fibrillation, hypertension, and major bleeding, says Pagel.

Other BTK inhibitors, known as reversible BTK inhibitors, are also under evaluation. At the 2019 ASH Annual Meeting, data were presented with ARQ-531, LOXO-305, and vecabrutinib. ARQ-531 has shown high response rates in a small number of patients, particularly in those with Richter’s transformation, says Pagel. LOXO-305 has also shown activity in patients who are resistant to irreversible BTK inhibitors, such as ibrutinib (Imbruvica) and acalabrutinib (Calquence). The last drug, vecabrutinib, has also shown encouraging data. With more follow-up, the field will be able to determine the optimal role of these agents, concludes Pagel.