Zanubrutinib for the treatment of Waldenström Macroglobulinemia.

Introduction: Waldenstrom Macroglobulinaemia (WM) is a heterogeneous, incurable condition which often relapses after chemoimmunotherapy. Novel therapies such as Bruton tyrosine-kinase (BTK) inhibitors have shown to be efficacious in treating WM but with an established, significant toxicity profile seen in the first-generation inhibitor Ibrutinib. Zanubrutinib is a selective, potent BTK inhibitor with the potential to reduce toxicity and improve efficacy. Areas covered: This review examines the activity of Zanubrutinib in treating treatment-naive and relapsed refractory WM and it's toxicity profile when compared to Ibrutinib. Outcomes from the AU003 and ASPEN studies will be examined in detail including a particular focus on MYD88WT and CXCR4WHIM disease. Strengths and weaknesses of this treatment approach will be highlighted and future directions for research will be identified. Expert opinion: Zanubrutinib induces deeper responses and have greater activity in MYD88WT and CXCR4WHIM WM. Zanubrutinib also has a favorable toxicity profile when compared to Ibrutinib. This may potentially translate to lower discontinuation rates, improved quality of life and ultimately longer progression-free survival in patients with WM.