Zanubrutinib Demonstrates Safety and Efficacy in Real-World CLL/SLL Treatment, Study Finds
Real-world data confirm the safety and effectiveness of zanubrutinib (brukinsa; BeOne) for patients with chronic lymphocytic leukemia (CLL) or small lymphocytic leukemia (SLL), regardless of prior treatment with ibrutinib (Imbruvica; Pharmacyclics and Johnson & Johnson). The findings, published in Cancer medicine, offer valuable insights into the drug’s performance outside of clinical trials.
A comprehensive analysis of patient data from the Kaiser Permanente health system revealed promising outcomes with zanubrutinib, a next-generation selective covalent Bruton tyrosine kinase inhibitor (BTKi). Initial clinical trials had already shown the drug to extend progression-free survival (PFS), but researchers, sought to further understand the impact of this shift in treatment strategy.
The study involved a retrospective review of pharmacy records, identifying 281 adult patients who had filled at least three months of prescriptions for zanubrutinib between October 2018 and September 2023. Patients participating in clinical trials or not continuously enrolled in the Kaiser Permanente Health Plan for at least six months prior to their first prescription were excluded from the analysis. Investigators tracked treatment duration, dose adjustments, discontinuations, mortality rates, and the occurrence of adverse events. Notably, 190 of the patients had previously been treated with ibrutinib.
The patient cohort was largely male (64%), with three-quarters identifying as White, and a median age of 71 years. Demographic characteristics and pre-existing cardiac conditions were generally similar between those with and without prior ibrutinib exposure, even though patients new to BTKi therapy tended to be slightly older, with a median age of 74 compared to 69 in the ibrutinib-experienced group.
Among those who switched from ibrutinib, the majority (57%) did so as a direct result of the formulary change implemented by Kaiser Permanente, while 12% transitioned due to disease progression on their previous therapy.
the rates of adverse events were comparable between patients receiving zanubrutinib and those on ibrutinib.However, the study found that treatment-limiting adverse events and cardiac-related adverse events were less frequent with zanubrutinib. For patients on ibrutinib, atrial fibrillation (1.6%) and fatigue (1.6%) were the most common reasons for discontinuing treatment. In contrast, cytopenia (1.4%) and rash/bruising (1%) were the primary causes for zanubrutinib discontinuation. Interestingly, 12 patients who had experienced adverse events while on ibrutinib saw a recurrence of the same events when switched to zanubrutinib.
The data indicated a lower incidence of atrial fibrillation with zanubrutinib; 11 patients on ibrutinib developed the condition, leading to treatment discontinuation in three cases, while four patients on zanubrutinib experienced atrial fibrillation, with one discontinuing therapy.
At the end of the follow-up period,79% of patients who initiated zanubrutinib remained on treatment. However, the length of follow-up varied considerably depending on whether patients were starting zanubrutinib as a first-line therapy or switching from ibrutinib.Of the 59 patients who discontinued treatment, the reasons included treatment-limiting adverse events (22 patients), disease progression (16 patients), death (12 patients), patient request (6 patients), and non-adherence (3 patients).
“to our knowledge, this is the largest cohort for real-world analysis of zanubrutinib treatment patterns with the unique component of formulary change in an integrated community oncology practice,” the investigators concluded. Their findings support the use of zanubrutinib as a safe and effective treatment option for CLL/SLL, both in patients previously treated with ibrutinib and in those initiating BTKi therapy. However,the researchers emphasized the need for further investigation with longer follow-up periods,more detailed reporting of low-grade adverse events,and studies exploring the optimal sequencing of different BTKi therapies.
