Switching from Ibrutinib to Zanubrutinib Maintains Efficacy and Safety in Waldenström Macroglobulinemia Patients
核心洞察
Interim data from 47 Waldenström macroglobulinemia (搜索) patients showed that 85% remained on zanubrutinib treatment after switching from ibrutinib at median 15.3 months follow-up.
The transition maintained high clinical efficacy with 96% best overall response rate, with responses either maintained in 63% or improved in 33% of patients.
Most ibrutinib-related adverse events did not recur or worsen on zanubrutinib, with no new hypertension (搜索) episodes and no recurrence of resolved atrial fibrillation (搜索).
Patients with Waldenström macroglobulinemia (搜索) (WM) who switch from ibrutinib to zanubrutinib can maintain comparable clinical outcomes while potentially experiencing improved safety profiles, according to interim data from a long-term extension study published in Blood Advances.
The analysis examined 47 patients who transitioned from ibrutinib treatment in the phase 3 ASPEN trial to zanubrutinib in the long-term extension study (BGB-3111-LTE1; NCT04170283). At a median follow-up of 15.3 months, 85% of patients remained on zanubrutinib treatment, demonstrating sustained tolerability of the newer BTK (搜索) inhibitor.
Efficacy Outcomes Maintained After Switch
Among 46 efficacy-evaluable patients, the transition to zanubrutinib yielded a high best overall response rate of 96%. Notably, responses were either maintained in 63% of patients or improved in 33% compared to their last response in the ASPEN study, suggesting that switching BTK (搜索) inhibitors does not compromise treatment effectiveness.
"Although 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," wrote study authors García-Sanz et al.
Safety Profile Shows Improvement
The safety analysis revealed that most ibrutinib treatment-emergent adverse events (TEAEs) of interest associated with BTK (搜索) inhibitors did not recur or worsen following the switch to zanubrutinib. Treatment-emergent adverse events occurred in 80.9% of patients, with 36.2% deemed treatment-related.
Grade ≥3 and serious TEAEs occurred in 23.4% and 12.8% of patients, respectively, during zanubrutinib treatment. Importantly, no new episodes of hypertension (搜索) occurred, and no resolved or ongoing atrial fibrillation (搜索) or flutter recurred or worsened after the transition.
ASPEN Trial Background
The findings build upon results from the ASPEN trial, a global, randomized, open-label phase 3 study that compared zanubrutinib versus ibrutinib in 201 patients with MYD88 (搜索)-mutated WM. The study included 164 patients with relapsed or refractory disease and 37 with treatment-naive disease.
Results from ASPEN showed higher rates of very good partial response with zanubrutinib compared to ibrutinib (28.4% vs 19.2%) as assessed by an independent review committee. Additional 2-year follow-up data confirmed the durability of this trend, with continued higher VGPR rates of 36.3% with zanubrutinib versus 25.3% with ibrutinib after 60 months of treatment.
Zanubrutinib's safety profile was favored over ibrutinib primarily due to fewer cardiovascular toxicities such as atrial fibrillation (搜索) and hypertension (搜索). The most common adverse events with zanubrutinib included neutropenia (搜索), upper respiratory infection, and diarrhea, while ibrutinib was associated with diarrhea, upper respiratory infection, contusion, and muscle spasms.
Study Limitations and Ongoing Research
The extension study includes patients from 15 parent studies of zanubrutinib and was initiated to facilitate long-term access to the drug for patients with B-cell malignancies while collecting long-term safety and efficacy data. Patients receive zanubrutinib at 160 mg twice daily or the last dose level received in the parent study.
The authors acknowledged limitations including the small sample size and nonrandomized nature of the analysis. Follow-up for the study remains ongoing to provide additional long-term data on the safety and efficacy of zanubrutinib in WM patients.