Dr. Shadman on the Emergence of Third-Generation 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 the emergence of third-generation BTK inhibitors in chronic lymphocytic leukemia (CLL).

During the 2020 ASH Annual Meeting and Exposition, findings from the phase 1/2 BRUIN study demonstrated promising efficacy with the third-generation, highly selective BTK inhibitor pirtobrutinib (LOXO-305) in heavily pretreated patients with CLL or small lymphocytic lymphoma.

In addition to the relapsed/refractory setting, LOXO-305 should be evaluated for patients with newly diagnosed CLL, says Shadman. Moreover, the combination of LOXO-305 plus venetoclax (Venclexta) and rituximab (Rituxan) is being evaluated in the BRUINN CLL-322 trial for patients with relapsed/refractory disease, Shadman explains.

LOXO-305 could have clinical utility in settings where current BTK inhibitors are not considered optimal, Shadman says. In addition, LOXO-305 appears to confer less toxicity compared with other BTK inhibitors, which makes it a potentially useful agent for other combination approaches, Shadman says.

Finally, other third-generation BTK inhibitors are under investigation in the CLL pipeline, concludes Shadman.