Dr Danilov on the Utility of Pirtobrutinib in CLL

Alexey Danilov, MD, PhD, hematologist-oncologist, associate director, Toni Stephenson Lymphoma Center, professor, Division of Leukemia, Department of Hematology and Hematopoietic Cell Transplantation, City of Hope, discusses the utility of pirtobrutinib (Jaypirca) in patients with chronic lymphocytic leukemia (CLL).

Pirtobrutinib has been investigated in the phase 1/2 BRUIN trial (NCT03740529), which enrolled approximately 700 patients, primarily those with CLL or mantle cell lymphoma, Danilov begins. The trial showed that pirtobrutinib was effective in patients with CLL who were refractory to covalent BTK inhibitors, he reports. Updates from this trial in the CLL population indicated better progression-free survival outcomes in patients not previously exposed to venetoclax (Venclexta) compared with those who had progressed on venetoclax, he says. Thus, the current FDA approval for pirtobrutinib in CLL is for patients who have been exposed and are refractory to both covalent BTK inhibitors and BCL-2 inhibitors, Danilov explains.

Notably, in December 2023, the FDA granted an accelerated approval to pirtobrutinib for the treatment of adult patients with CLL or small lymphocytic lymphoma who have received at least 2 prior lines of therapy, including a BTK inhibitor and a BCL-2 inhibitor, based on data from the phase 1/2 trial.

In practice, pirtobrutinib is also used in patients who haven’t been treated with venetoclax, which is considered an appropriate treatment approach, he continues. Despite relatively short follow-up periods, the drug has proven to be safe and well tolerated, with most patients remaining on the treatment for an average of 2 years, Danilov explains, adding that many patients have responded positively to pirtobrutinib after progressing on other BTK inhibitors.

Currently, multiple ongoing trials are investigating pirtobrutinib in earlier lines of therapy, Danilov continues. Although the BRUIN study included few BTK inhibitor–naive patients, the results showed good efficacy with long-term follow-up in this population, despite the small sample size, he states. Further investigations will continue to explore the effectiveness of pirtobrutinib in CLL, Danilov concludes.