Zanubrutinib for the treatment of adults with Waldenstrom macroglobulinemia

ABSTRACT

Introduction

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.

Areas covered

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.

Expert opinion

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.

KEYWORDS:

• Acalabrutinib
• Bruton tyrosine kinase
• BTK
• ibrutinib
• Waldenström macroglobulinemia
• zanubrutinib

Article highlights

• Bruton tyrosine kinase (BTK) inhibition plays an important role in the treatment of patients with Waldenström macroglobulinemia.

• The currently available BTK inhibitors share a side effect profile that includes infection, cytopenias, bleeding, and atrial arrhythmia.

• Ibrutinib was the first FDA-approved treatment for Waldenström macroglobulinemia (WM).

• Zanubrutinib, also FDA-approved for the treatment of WM, offers an equivalent hematologic response rate with an improved side effect profile.

Declaration of interest

S Sarosiek has received research funding from Acrotech Biopharma and ADC Therapeutics, JJ Castillo has received research funding and consulting fees from Abbvie, AstraZeneca, Beigene, Janssen, Pharmacyclics, Polyneuron, Roche and TG Therapeutics. AR Branagan has received research funds and consulting fees from Pharmacyclics/Janssen, Genzyme, Adaptive Biotechnologies, BeiGene, Karyopharm Therapeutics and CSL Behring. SP Treon has received research funds or consulting fees from Abbvie, Beigene, BMS, Janssen, Lilly, Pharmacyclics and X4. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

The authors have no funding to report.