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The development of Bruton tyrosine kinase (BTK) inhibitors has significantly changed the treatment landscape for patients with Waldenström macroglobulinemia (WM). Ibrutinib was the first BTK inhibitor to receive FDA approval for this disease, but in recent years additional more selective BTK inhibitors have become available. Zanubrutinib, the most recently FDA-approved therapy for WM, has demonstrated comparable efficacy regarding hematologic response, but with an improved side effect profile compared to other BTK inhibitors. In this review, we highlight the pivotal studies that have formed the foundation for the use of zanubrutinib in WM, including safety and efficacy data from prospective clinical trials of the currently available BTK inhibitors. BTK inhibitors are very effective in WM and have an overall response rate higher than 90%. The side effect profile of these medications is manageable but does include a risk of atrial fibrillation, infection, and bleeding. The newer BTK inhibitors, such as acalabrutinib and zanubrutinib, are known to have less off-target effects and are potential treatment options. BTK inhibitors should be considered as a treatment option in treatment-naïve and previously treated disease depending on the individual patient preferences, comorbidities, and molecular profile.

Zanubrutinib for the treatment of adults with Waldenstrom macroglobulinemia