Zanubrutinib Safe, Effective in Real-World CLL/SLL Cohort

New real-world data support the safety and efficacy of zanubrutinib (Brukinsa; BeOne) in patients with chronic lymphocytic leukemia (CLL) or small lymphocytic leukemia (SLL), regardless of whether they have previously been treated with ibrutinib (Imbruvica; Pharmacyclics and Johnson & Johnson).

The findings, which were based on patients in the Kaiser Permanente health system, were published in Cancer Medicine.¹

In clinical trials, the next-generation selective covalent Bruton tyrosine kinase inhibitor (BTKi) zanubrutinib was shown to extend progression-free survival (PFS) compared to chemoimmunotherapy in treatment-naive patients with CLL or SLL.² It also improved outcomes in relapsed or refractory patients, compared to ibrutinib.³

Corresponding author Jahan Tavakoli, MD, of Kaiser Permanente San Francisco, and colleagues, explained that those results led Kaiser Permanente Northern California to replace ibrutinib with zanubrutinib as the preferred BTKi for CLL/SLL, starting in August 2021.¹ The FDA later approved the therapy for CLL/SLL in 2023.

Tavakoli and colleagues aimed to understand the impact of zanubrutinib use among patients in their health system who were treatment-naive, BTKi-naive, or ibrutinib-treated. They consulted pharmacy records to identify adult patients who filled at least 3 months of prescriptions for zanubrutinib between October 2018 and September 2023 at a Kaiser Permanente pharmacy. Patients who were participating in a clinical trial or who were not on the Kaiser Permanente Health Plan within 6 months of their first prescription were excluded.

The investigators tracked a number of metrics, including treatment duration, dose modifications and discontinuations, mortality, and adverse events. They identified a total of 281 patients who met the study’s inclusion criteria, of whom 190 had previously been on ibrutinib.

Most patients in the cohort (64%) were male, three-quarters were White, and the median age was 71 years. Demographics and prior cardiac comorbidities were similar between the patients with and without prior ibrutinib, though the patients without previous ibrutinib had a median age of 74, compared to 69 in the other group.

Among those who switched from ibrutinib, the authors said most did so as a result of the practice’s change (57%), though 12% changed due to progression on their previous therapy.

Overall, Tavakoli and colleagues found that rates of adverse events were similar among patients on zanubrutinib and those on ibrutinib. However, they found rates of treatment-limiting adverse events and cardiac adverse events were lower on zanubrutinib. For ibrutinib, the most common treatment-limiting adverse events were atrial fibrillation (1.6%) and fatigue (1.6%). For zanubrutinib, the most common treatment-limiting adverse events were cytopenia (1.4%) and rash/bruising (1%). Among the 69 patients who had treatment-emergent adverse events while on ibrutinib, 12 patients experienced a recurrence of the same adverse event while on zanubrutinib.

The authors noted that 11 patients on ibrutinib developed atrial fibrillation, and 3 of those patients discontinued the therapy. Four patients developed atrial fibrillation on zanubrutinib, and one discontinued.

Overall, 79% of patients who received zanubrutinib remained on treatment at the end of follow-up. However, the median follow-up time varied significantly, depending on whether the patients started on zanubrutinib or switched from ibrutinib. Among the 59 patients who discontinued, 22 did so as a result of treatment-limiting adverse events, 16 discontinued due to progression, 12 patients discontinued due to death, 6 patients requested to stop, and 3 patients discontinued due to non-adherence.

“In summary, 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.

They said their data show that zanubrutinib is safe both in patients with prior ibrutinib use and in those without. However, they said additional research is needed with longer follow-ups, enhanced reporting of low-grade adverse events, and sequencing of multiple lines of BTKi therapy.

References

1. Krackeler ML, Chee BH, Orchanian AK, et al. Real-world treatment patterns and outcomes of zanubrutinib in chronic lymphocytic leukemia and small lymphocytic leukemia (CLL/SLL). Cancer Med. 2025;14(20):e71300. doi:10.1002/cam4.71300

2. Tam CS, Brown JR, Kahl BS, et al. Zanubrutinib versus bendamustine and rituximab in untreated chronic lymphocytic leukaemia and small lymphocytic lymphoma (SEQUOIA): a randomised, controlled, phase 3 trial. Lancet Oncol. 2022;23(8):1031-1043. doi:10.1016/S1470-2045(22)00293-5

3. Brown JR, Eichhorst B, Hillmen P, et al. Zanubrutinib or ibrutinib in relapsed or refractory chronic lymphocytic leukemia. N Engl J Med. 2023;388(4):319-332. doi:10.1056/NEJMoa2211582