Outcomes following transition from ibrutinib to zanubrutinib in patients with Waldenström macroglobulinemia from ASPEN Open Access

• In patients who transitioned from ibrutinib to zanubrutinib after ASPEN, BTK inhibitor-associated treatment-emergent AEs were rare

• Overall response at the end of ASPEN was maintained or improved in 96% (n=44/46) of efficacy-evaluable patients in the BGB-3111-LTE1 study

Zanubrutinib is a next-generation covalent Bruton tyrosine kinase (BTK) inhibitor designed to provide complete and sustained BTK occupancy for efficacy across disease-relevant tissues, with fewer off-target adverse events (AEs) than other covalent BTK inhibitors. In the phase 3 ASPEN study (BGB-3111-302), comparable efficacy and a favorable safety profile versus ibrutinib were demonstrated in patients with MYD88-mutated Waldenström macroglobulinemia (WM), leading to approval of zanubrutinib for patients with WM. BGB-3111-LTE1 (LTE1) is a long-term extension study to which eligible patients, including patients from comparator treatment arms, could enroll following participation in various parent studies of zanubrutinib to treat B-cell malignancies. Here, safety and efficacy are reported in the 47 patients who transitioned from ibrutinib treatment in ASPEN to zanubrutinib in LTE1. The median time from ibrutinib treatment initiation to LTE1 enrollment was 50.4 months (range, 26-59.3). At median LTE1 study follow-up of 15.3 months (range, 6.0-35.1), 85% of patients in this subgroup remained on zanubrutinib treatment. The median zanubrutinib treatment duration was 15.3 months. Despite advanced and increasing age, most ibrutinib treatment-emergent AEs of interest for BTK inhibitors did not recur or worsen with zanubrutinib. WM disease response was maintained or improved in 96% (44/46) of efficacy-evaluable patients (n = 2 converted to negative immunofixation). While limited by sample size and nonrandomized/ad-hoc analyses, data suggest that patients who tolerate ibrutinib may switch to zanubrutinib without compromising safety or efficacy. Long-term follow-up is ongoing. Registration: NCT03053440, NCT04170283.