The following is a summary of “Zanubrutinib Versus Ibrutinib in Symptomatic Waldenström Macroglobulinemia: Final Analysis From the Randomized Phase III ASPEN Study,” published in the November 2023 issue of Oncology by Dimopoulos, et al.

The ASPEN study’s phase III trial initially demonstrated the comparable efficacy and enhanced safety profile of zanubrutinib compared to ibrutinib in patients with Waldenström macroglobulinemia (WM). For a study, researchers sought to provide long-term follow-up outcomes from the ASPEN study. The primary endpoint was the sum of very good partial response (VGPR) + complete response (CR) rates, with secondary and exploratory endpoints also considered.

Cohort 1 consisted of 201 patients (myeloid differentiation primary response 88–mutant WM: 102 receiving zanubrutinib; 99 receiving ibrutinib), while cohort 2 included 28 patients (myeloid differentiation primary response 88 wild-type WM: 28 zanubrutinib; 26 efficacy evaluable). The follow-up duration was a median of 44.4 months.

At the 44.4-month median follow-up, VGPR + CR rates were 36.3% with zanubrutinib versus 25.3% with ibrutinib in cohort 1 and 30.8% with one CR in cohort 2. In patients with CXC motif chemokine receptor 4 mutation, VGPR + CR rates were 21.2% with zanubrutinib versus 10.0% with ibrutinib (cohort 1). Median progression-free survival and overall survival were not reached. Any-grade adverse events (AEs) such as diarrhea (34.7% vs. 22.8%), muscle spasms (28.6% vs. 11.9%), hypertension (25.5% vs. 14.9%), atrial fibrillation/flutter (23.5% vs. 7.9%), and pneumonia (18.4% vs. 5.0%) were more common with ibrutinib versus zanubrutinib. Neutropenia (20.4% vs. 34.7%) was less common with ibrutinib versus zanubrutinib (cohort 1). Zanubrutinib was associated with a lower risk of AE-related treatment discontinuation.

The findings affirmed the enduring high-quality response and tolerability of zanubrutinib in treating Waldenström macroglobulinemia.

Source: ascopubs.org/doi/full/10.1200/JCO.22.02830