Longevity & AgingZanubrutinib Outperforms Ibrutinib in Waldenström Macroglobulinemia with Better Safety
Waldenström Macroglobulinemia (WM) is a rare IgM-secreting B-cell lymphoma driven largely by MYD88 mutations. The second-generation BTK inhibitor zanubrutinib was designed to improve on ibrutinib's efficacy and tolerability by more selectively targeting BTK. The landmark ASPEN phase III trial showed zanubrutinib achieved VGPR or better in 36.3% of patients versus 25.3% with ibrutinib at 44 months follow-up, with significantly fewer cardiovascular adverse events including atrial fibrillation and hypertension. Patients with CXCR4 or TP53 mutations still fare worse, highlighting unmet needs. This review synthesizes clinical trial data, pharmacology, genetic subtype impacts, and adverse event management to guide real-world use of zanubrutinib in WM.
