Zanubrutinib for treating Waldenstrom's macroglobulinaemia

Zanubrutinib for treating Waldenstrom's macroglobulinaemia (WM)

Zanubrutinib is a next-generation Bruton tyrosine kinase (BTK) inhibitors that was developed to achieve BTK inhibiting efficacy while reducing the off-target adverse events documented with ibrutinib therapy

• has high specificity for the BTK adenosine triphosphate binding site for cysteine 481, zanubrutinib covalently binds to this site, resulting in irreversible, sustainable kinase inhibition
• ibrutinib, showed great efficacy in treating WM
  • however, response rates were dependent on whether patients had the CXCR4 mutation, a molecular aberration that may confer resistance to BTK inhibitors
  • ibrutinib's toxicities, most notably hypertension and atrial arrhythmia, led to dose reductions or discontinuation
  • toxicity profile of ibrutinib can be attributed to the inhibition of additional kinases that are structurally related to BTK

NICE state:

• Zanubrutinib is recommended as an option for treating Waldenstrom's macroglobulinaemia in adults who have had at least 1 treatment, only if:
  • bendamustine plus rituximab is also suitable and
  • the company provides it according to the commercial arrangement

Reference:

• Deshpande A, Munoz J. Zanubrutinib in Treating Waldenstrom Macroglobulinemia, the Last Shall Be the First. Ther Clin Risk Manag. 2022 Jun 23;18:657-668.
• NICE (October 2022). Zanubrutinib for treating Waldenstrom's macroglobulinaemia