Dr Deng on the Benefits of Pirtobrutinib in CLL

Changchun Deng, MD, PhD, associate professor, hematology/oncology, University Hospitals Seidman Cancer Center; member, Immune Oncology Program, Case Comprehensive Cancer Center, discusses the mechanism of action of the noncovalent BTK inhibitor pirtobrutinib (Jaypirca) and the advantages that are associated with this agent for the treatment of patients with previously treated chronic lymphocytic leukemia (CLL).

When determining what treatment a patient with CLL should receive, oncologists should consider the patient’s overall health, cardiac function, and treatment history, Deng says. One option for these patients is the novel noncovalent BTK inhibitor pirtobrutinib, which received accelerated FDA approval in 2023 for the treatment of adult patients with CLL or small lymphocytic lymphoma (SLL) who have received 2 or more prior lines of therapy, including a BCL-2 inhibitor and a BTK inhibitor.

Although all BTK inhibitors share the same target, noncovalent agents target BTK differently than covalent BTK inhibitors, and can therefore be used in patients who have previously received covalent agent, Deng notes. In the CLL/SLL cohort (n = 110) of the pivotal phase 1/2 BRUIN trial (NCT03740529), 98% of patients had received 2 or more prior lines of systemic therapy. At an estimated median follow-up of 15.7 months, pirtobrutinib elicited an overall response rate of 72% (95% CI, 63%-80%), all of which were partial responses. The median time to response was 3.7 months (range, 1.7-27.9), and the median duration of response was 12.2 months (95% CI, 9.3-14.7).

Furthermore, the safety profile of pirtobrutinib is favorable when compared with that of covalent BTK inhibitors that are FDA approved in CLL, such as ibrutinib (Imbruvica), acalabrutinib (Calquence), and zanubrutinib (Brukinsa), Deng emphasizes. For instance, pirtobrutinib is associated with lower levels of cardiac toxicity, Deng concludes. The most common serious AEs with pirtobrutinib in the BRUIN trial were pneumonia (18%), COVID-19 (9%), febrile neutropenia (7%), and sepsis (7%).