Dr Koff on Toxicities Associated With Pirtobrutinib in MCL

Jean L. Koff, MD, MS, associate professor, Department of Hematology and Medical Oncology; clinical investigator, Bone Marrow and Stem Cell Transplant Center, Emory University School of Medicine; member, Discovery and Developmental Therapeutics Research Program, Winship Cancer Institute, Emory University, discusses toxicities associated with pirtobrutinib (Jaypirca) in patients with mantle cell lymphoma (MCL).

In January 2023, the FDA approved pirtobrutinib for the treatment of adult patients with relapsed/refractory MCL who have undergone at least 2 lines of systemic therapy, including a BTK inhibitor, Koff begins. This approval was granted under the FDA's accelerated approval pathway and was supported by data from the phase 1/2 BRUIN trial (NCT03740529), which was an open-label, single-arm study, she explains. In BRUIN, pirtobrutinib elicited an overall response rate of 50% (95% CI, 41%-59%) in patients who received the agent at a daily dose of 200 mg once daily (n = 120) and a complete response rate of 13%, as well as a partial response rate of 38%.

During the BRUIN trial, pirtobrutinib was primarily associated with constitutional symptoms, such as fatigue, along with gastrointestinal adverse effects (AEs), such as diarrhea, Koff continues. These AEs were generally manageable, she says, adding that as with other BTK inhibitors, infections were observed, which is common among patients undergoing lymphoma treatment. However, the incidence of severe infections specifically attributable to pirtobrutinib was low, she notes. Bruising was noted among the patients, but no cases of severe bruising or hemorrhage were reported, Koff reports.

Atrial fibrillation or flutter, which can be a concern with BTK inhibitors, occurred at a very low rate with pirtobrutinib, she expands. Similarly, hypertension is another AE that requires monitoring in patients receiving BTK inhibitors, Koff states, adding that the incidence of pirtobrutinib-related hypertension was very low, with no instances of severe-grade high blood pressure. Community oncologists should be aware of these potential AEs when considering pirtobrutinib for their patients but can be reassured by the relatively low incidence of severe AEs, she concludes.