Dr Shadman on Zanubrutinib in CLL/SLL Intolerant to Prior BTK Inhibitors

Mazyar Shadman, MD, MPH, physician, associate professor, Division of Medical Oncology, University of Washington School of Medicine, associate professor, Clinical Research Division, Fred Hutchinson Cancer Center, discusses preliminary long-term findings from the evaluation of zanubrutinib (Brukinsa) in previously treated patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) who were intolerant to ibrutinib (Imbruvica) and/or acalabrutinib (Calquence).

At the 2023 iwCLL Annual Meeting, Shadman and colleagues presented follow-up data from a phase 2 trial (NCT04116437), which evaluated zanubrutinib in patients with pretreated B-cell malignancies who were intolerant of other BTK inhibitors. Previously reported findings from this study have shown that zanubrutinib elicited efficacy and was well tolerated in patients who discontinued ibrutinib and acalabrutinib due to adverse effects (AEs) associated with their treatment, Shadman begins.

This updated analysis showed that most patients with CLL/SLL could receive treatment with zanubrutinib without encountering a recurrence of the AEs that had prompted discontinuation of a prior BTK inhibitor, he says. In patients with CLL/SLL who were intolerant to ibrutinib, 65 intolerance-related AEs did not recur during treatment with zanubrutinib, 22 recurred at a lower grade, and 8 recurred at the same grade. In patients with CLL/SLL who were intolerant to acalabrutinib, 15 intolerance-related AEs did not recur with zanubrutinib, 2 recurred at lower grades, and 4 recurred at the same grade.

Safety findings for zanubrutinib showed that any-grade treatment-emergent AEs (TEAEs) occurred in 93.4% of patients (n = 61), including 50.8% of patients who had grade 3 or higher TEAEs. The most common grade 3 or higher TEAEs were neutropenia (11.5%), COVID-19 (6.6%), and pneumonia (6.6%). TEAEs led to treatment discontinuation in 8.2% of patients, and 1 TEAE led to death (COVID-19 pneumonia).

This study holds significant practical implications, especially for health care providers treating patients with CLL, as this could represent a treatment option for patients who derive benefit from BTK inhibitors but face challenges due to AEs, Shadman emphasizes. Long-term follow-up data from this study showed that in patients with CLL/SLL evaluable for efficacy (n = 57), zanubrutinib elicited an overall response rate of 71.9% (95% CI, 58.5%-83.0%) and a disease control rate of 94.7% (95% CI, 85.4%-98.9%).

Findings from this study continue to reinforce the notion that tailoring treatments to individual patients is essential when making decisions for those with CLL, Shadman says. These findings contribute to the growing body of evidence supporting personalized medicine approaches, underscoring the importance of ongoing clinical trials to refine and expand treatment options for those with CLL who are intolerant to certain BTK inhibitors, he concludes.