Dr Danilov on the Current and Potential Use 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 current and potential utility for the BTK inhibitor pirtobrutinib (Jaypirca) for patients with chronic lymphocytic leukemia (CLL). 

Pirtobrutinib was first evaluated 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 demonstrated high efficacy of pirtobrutinib in patients with CLL who were refractory to covalent BTK inhibitors, leading to the FDA approval of pirtobrutinib in December 2023 for the treatment of adult patients with CLL or small lymphocytic lymphoma who received 2 or more prior lines of therapy, including a BTK inhibitor and a BCL2 inhibitor. A recent update from the trial showed that progression-free survival (PFS) was better in patients who had not been exposed to venetoclax (Venclexta) compared with those who had progressed on venetoclax, he adds.

Despite the agent’s current indication following the regulatory approval, in clinical practice, pirtobrutinib is also being used in patients who have not yet received venetoclax, he says. The drug has shown a favorable safety profile, and although follow-up data are still relatively short, most patients remain on the treatment for about 2 years, Danilov says, adding that this reflects the agent’s tolerability and safety. Multiple cases of patients responding to pirtobrutinib after progression on other BTK inhibitors have been reported, underscoring its potential as an effective option even after resistance to prior therapies, he states.

Ongoing clinical trials are exploring the use of pirtobrutinib in earlier lines of therapy, especially in BTK inhibitor-naive patients, Danilov continues. Although the BRUIN trial showed promising long-term efficacy data, the number of BTK inhibitor-naive patients included in the study was small, he notes. As a result, further investigations are necessary to assess the drug's efficacy in this population. These ongoing studies aim to better define pirtobrutinib's role in earlier treatment settings and broaden its application for patients with CLL, Danilov concludes.