Zanubrutinib is well tolerated and effective in patients with CLL/SLL intolerant of ibrutinib/acalabrutinib: updated results

作者：Mazyar Shadman, John M. Burke, Jennifer L. Cultrera, Habte Yimer, Syed F. Zafar, Jamal Misleh, Subramanya S. Rao, Charles M. Farber, Aileen Cleary Cohen, Hui Yao, Adam Idoine, Qi An, Ian W. Flinn, Jeff P. Sharman · 发表于：Blood Advances · 年份：2025 · DOI：10.1182/bloodadvances.2024015493 · 被引用次数：12 · 研究领域：Chronic Lymphocytic Leukemia Research

ABSTRACT: Bruton tyrosine kinase (BTK) inhibitors such as ibrutinib (ibr) revolutionized chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) treatment, although treatment-related toxicities limit the use of some BTK inhibitors. Zanubrutinib, a potent next-generation BTK inhibitor, has higher selectivity than ibrutinib or acalabrutinib. The ongoing phase 2, single-arm BGB-3111-215 study investigates the safety and efficacy of zanubrutinib in patients with B-cell malignancies who are intolerant of ibrutinib and/or acalabrutinib. Here, results in patients with CLL/SLL are presented. Patients received zanubrutinib 160 mg twice daily or 320 mg once a day. With a 34.5-month median follow-up, 71 patients (ibrutinib intolerant only, n = 44; acalabrutinib intolerant only, n = 17; ibrutinib and acalabrutinib intolerant, n = 10) received ≥1 zanubrutinib dose. On zanubrutinib, 54% (28/52) of ibrutinib-intolerant patients and 70% (19/27) of acalabrutinib-intolerant patients experienced no recurrence of intolerance adverse events (AEs); 60% and 72% of intolerance AEs did not recur, respectively. Of recurrent ibrutinib-intolerance AEs, 64% were lower grade; 44% of acalabrutinib-intolerance AEs were lower grade. No intolerance AEs recurred at a higher grade with zanubrutinib. The most common recurrent ibrutinib-intolerance and acalabrutinib-intolerance AEs were fatigue and diarrhea, respectively. The most common treatment-emergent AEs (TEAEs) with zanubrutinib were fatigue (32%...