A new noncovalent BTK inhibitor, pirtobrutinib (Jaypirca), has been making strides in the treatment of previously treated chronic lymphocytic leukemia (CLL) patients. Dr. Changchun Deng, an associate professor in hematology/oncology at University Hospitals Seidman Cancer Center, sheds light on the mechanism of action of pirtobrutinib and its advantages for patients in need.
When deciding on CLL treatment options, factors such as overall health, cardiac function, and treatment history play a crucial role, according to Deng. Pirtobrutinib, which received accelerated FDA approval in 2023 for adult patients with CLL or small lymphocytic lymphoma (SLL) who have undergone 2 or more prior lines of therapy, including a BCL-2 inhibitor and a BTK inhibitor, emerges as a promising option.
Deng highlights that while all BTK inhibitors target the same enzyme, noncovalent agents like pirtobrutinib approach BTK differently than covalent inhibitors. This distinction allows pirtobrutinib to be used in patients who have previously been treated with a covalent agent. In a pivotal phase 1/2 BRUIN trial involving a CLL/SLL cohort, pirtobrutinib demonstrated an impressive overall response rate of 72%, all of which were partial responses. The medication showed a median time to response of 3.7 months and a median duration of response of 12.2 months.
Moreover, pirtobrutinib stands out for its favorable safety profile compared to other FDA-approved covalent BTK inhibitors like ibrutinib (Imbruvica), acalabrutinib (Calquence), and zanubrutinib (Brukinsa), Deng points out. The noncovalent inhibitor is linked to lower levels of cardiac toxicity, making it a promising option for CLL patients. The most common serious adverse events observed in the BRUIN trial with pirtobrutinib included pneumonia (18%), COVID-19 (9%), febrile neutropenia (7%), and sepsis (7%).
In conclusion, pirtobrutinib’s unique mechanism of action and favorable safety profile position it as a valuable addition to the treatment landscape for patients with previously treated CLL.
