Dr Brown on the Potential for Pirtobrutinib to Address Treatment Discontinuation in CLL

Jennifer R. Brown, MD, PhD, director, Chronic Lymphocytic Leukemia Center, Dana-Farber Cancer Institute, the Worthington and Margaret Collette Professor of Medicine in the Field of Hematologic Oncology, Harvard Medical School, discusses how pirtobrutinib (Jaypirca) may one day influence treatment discontinuation due to toxicities or intolerance in patients with chronic lymphocytic leukemia (CLL).

Treatment discontinuation rates among patients with CLL being treated with BTK inhibitors vary depending on the duration of treatment, Brown begins. With newer BTK inhibitors, discontinuation rates due to adverse effects (AEs) following approximately 3 years of treatment range from 20% to 25%, while discontinuation due to disease progression sits at approximately 15%, Brown reports. Notably, AE rates have improved with pirtobrutinib compared with earlier drugs like ibrutinib (Imbruvica). It's significant that more patients discontinue treatment due to AEs rather than disease progression while actively taking BTK inhibitors, she says.

In December 2023, the FDA approved pirtobrutinib (Jaypirca) for the treatment of adult patients with CLL or small lymphocytic lymphoma (SLL) who received 2 or more prior lines of therapy, including a BTK inhibitor and a BCL2 inhibitor. The approval was based on data from the phase 1/2 BRUIN trial (NCT03740529), where pirtobrutinib demonstrated an overall response rate of 72% among patients with CLL/SLL (n = 108).

One of the key advantages of pirtobrutinib is its potential ability to address both disease progression and treatment intolerability, Brown states. Patients who had discontinued prior therapies and met other eligibility criteria were enrolled onto the BRUIN trial, exhibiting positive responses with pirtobrutinib, Brown details. This suggests that patients can benefit from pirtobrutinib regardless of whether they have experienced disease progression, she explains.

Additionally, pirtobrutinib exhibited a favorable safety profile in the BRUIN trial, with a comparable AE profile to other BTK inhibitors and potentially lower rates of cardiovascular events, Brown continues. This favorable safety profile positions pirtobrutinib as a well-tolerated treatment option for patients with CLL or SLL, potentially offering sustained remission and addressing the challenges of AEs associated with second-generation covalent inhibitors zanubrutinib (Brukinsa) and acalabrutinib (Calquence), Brown emphasizes. Initial data suggest that many patients can achieve and sustain remission for at least a year with pirtobrutinib.