Zanubrutinib Associated With Lower Switching Rates vs Other Covalent BTK Inhibitors in CLL/SLL

Javier Pinilla-Ibarz, MD, PhD

Findings from a real-world study showed that zanubrutinib (Brukinsa) was associated with lower rates of treatment switching and patients receiving subsequent therapy compared with acalabrutinib (Calquence) and ibrutinib (Imbruvica) in patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL).

Data presented at the 2024 SOHO Annual Meeting showed that irrespective of whether patients were treated with a BTK inhibitor in the first or second line, the switching rate at 60 days or less and 61 to 89 days was lower for patients receiving zanubrutinib compared with those receiving acalabrutinib and ibrutinib (for both first and second line, P < .0001).

In the first-line setting, the rate of patients switching therapies before 90 days was 10.2% for zanubrutinib (n = 157) compared with 20.5% for acalabrutinib (n = 1238) and 15.9% for ibrutinib (n = 1421). In the second-line setting, the switch rate before 90 days was 7.5% for zanubrutinib (n = 107), 13.2% for acalabrutinib (n = 672), and 21.1% for ibrutinib (n = 474).

“This study highlighted the real-world advantages of zanubrutinib compared [with] other BTK inhibitors in patients with CLL/SLL,” lead study author Javier Pinilla-Ibarz, MD, PhD, and colleagues, wrote in a poster presentation of the data. “Future studies with extended follow-up are necessary to facilitate evaluation of emerging therapies and to assess long-term real-world outcomes.”

Pinilla-Ibarz is a senior member and head of Lymphoma Section in the Department of Malignant Hematology at Moffitt Cancer Center in Tampa, Florida.

The retrospective study utilized the Integra Connect database, which includes electronic medical records from community-based oncology practices, to evaluate real-world switching and sequencing to next-line therapies among patients with CLL or SLL initiating BTK inhibitors in the first-line or second-line setting.

The study period spanned from December 1, 2019, to March 31, 2023, with an index period between January 1, 2020, and February 28, 2023. Investigators gathered data for patients at least 18 years of age with CLL or SLL who initiated treatment with acalabrutinib, ibrutinib, or zanubrutinib during the index period.

On the study, a total of 2816 patients initiated first-line BTK inhibitor therapy; 1253 patients began second-line treatment. In the first-line setting, ibrutinib was the most frequently used BTK inhibitor (50.5%), followed by acalabrutinib (44.0%) and zanubrutinib (5.6%). In the second-line setting, acalabrutinib was most commonly used (53.6%), followed by ibrutinib (37.8%) and zanubrutinib (8.54%).

Demographic and clinical characteristics were assessed at baseline, and study authors noted that there were no significant differences in age, sex, payer type, or Rai stage among the 3 cohorts. The median follow-up duration in the first-line setting was 123 days (interquartile range [IQR], 63-335) for zanubrutinib, 406 days (IQR, 196-659) for acalabrutinib, and 637 days (IQR, 326-921) for ibrutinib (P <.0001). In the second-line setting, median follow-up durations were 133 days (IQR, 62-385) for zanubrutinib, 503 days (IQR, 265-799) for acalabrutinib, and 524 days (IQR, 259-856) for ibrutinib (P <.0001).

Treatment switching was measured by identifying patients who initiated another treatment within the same line or advanced to the next line of therapy within 90 days. Sequencing to the next line of therapy was calculated using Kaplan-Meier analysis, and the proportion of patients receiving the next line of therapy at 180 days was reported.

Additional data showed the switching rates before 60 days in the first-line setting were 10.2% for zanubrutinib, 17.1% for acalabrutinib, and 13.1% for ibrutinib. The respective switching rates from 61 to 89 days were 0%, 3.4%, and 2.5%. In the second-line setting, the switching rates before 60 days were 7.5% for zanubrutinib, 10.7% for acalabrutinib, and 17.1% for ibrutinib. The switching rates from days 61 to 89 were 0%, 2.5%, and 4.0%, respectively.

The proportion of patients who received their next line of therapy at 180 days was lowest for those treated with zanubrutinib. In the first-line setting, 13.9% of patients treated with zanubrutinib received next-line therapy by day 180 compared with 24.5% of patients treated with acalabrutinib and 21.1% of patients treated with ibrutinib. In the second-line setting, these rates were 9.1% for zanubrutinib, 18.6% for acalabrutinib, and 29.2% for ibrutinib.

Authors noted that the study was limited by a United States–based population, which may not be applicable to all patient populations. They also explained data may be limited by the real-world nature of the study.

Reference

Pinilla-Ibarz J, Xue M, Wu E, et al. Real-world treatment switching and sequencing to next line of therapy of zanubrutinib, acalabrutinib, and ibrutinib in CLL/SLL. Presented at: 2024 SOHO Annual Meeting; September 4-7, 2024; Houston, TX. Abstract CLL-354.