Dr Koff on the Safety Profile of Pirtobrutinib in Pretreated CLL/SLL

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 the safety profile of pirtobrutinib (Jaypirca) according to data from the phase 1/2 BRUIN trial (NCT03740529) in chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL).

The FDA granted accelerated approval to pirtobrutinib in December 2023 for the treatment of adult patients with CLL or SLL who previously received at least 2 prior lines of therapy, including a BTK inhibitor and a BCL-2 inhibitor. This regulatory decision was supported by updated findings from the phase 1/2 BRUIN trial (NCT03740529).

In the BRUIN trial, pirtobrutinib demonstrated favorable tolerability, Koff begins. The most commonly observed adverse effects (AEs) were constitutional symptoms such as fatigue, Koff reports. Diarrhea occurred in 28.4% of patients at a generally low grade and cough was reported in 27.3% of patients, she adds. Similar to other covalent BTK inhibitors, bruising and bleeding events were noted with pirtobrutinib; these were typically mild, Koff notes.

Other AEs of interest with BTK inhibitors, such as hypertension, were observed infrequently in the CLL cohort, Koff continues. The incidence of treatment-related hypertension was 3.5%, and few grade 3 or higher events (0.4%) were reported, she says, adding that the rates of treatment-related atrial fibrillation and flutter were also low at 1.4%. Neutropenia emerged as a notable cytopenia associated with pirtobrutinib, occurring in 28.4% of patients with CLL/SLL as a grade 3 or higher AE, Koff states. This AE is commonly observed when administering the majority of lymphoma-directed therapies, she notes.

These findings underscore pirtobrutinib's manageable safety profile in this heavily pretreated population, Koff emphasizes. Overall, the approval of pirtobrutinib represents a significant advancement in treatment options for patients with CLL and SLL who have exhausted other therapeutic options, providing a new targeted treatment approach with encouraging tolerability and efficacy data from the BRUIN trial.