Drug Class
- Second-generation BTK inhibitor (Bruton’s tyrosine kinase inhibitor)
- More selective than ibrutinib → designed to reduce off-target toxicity (e.g., atrial fibrillation, bleeding).
FDA-Approved Indications (as of 2025)
- Chronic lymphocytic leukemia (CLL) / small lymphocytic lymphoma (SLL)
- Waldenström macroglobulinemia (WM)
- Mantle cell lymphoma (MCL) (accelerated approval after ≥1 prior therapy)
- Marginal zone lymphoma (MZL) (after ≥1 anti-CD20–based regimen)
Typical Dosing
- 160 mg orally twice daily
OR - 320 mg orally once daily
(with or without food). - Continue until progression or unacceptable toxicity.
Key Toxicities
- Hematologic: neutropenia, thrombocytopenia, anemia
- Infections: bacterial, viral, fungal (consider prophylaxis in high-risk patients)
- Bleeding risk (less than ibrutinib but still present)
- Cardiac: atrial fibrillation/flutter, hypertension (lower incidence vs ibrutinib)
- Second primary malignancies (skin cancers)
- Other: diarrhea, rash, fatigue
Monitoring / Supportive Care
- CBC, liver function tests
- Monitor for bleeding and arrhythmias
- HBV screening before anti-CD20 if used in combination
- Infection prophylaxis in select cases
Clinical Pearls
- Better tolerated than ibrutinib: head-to-head trials (e.g., ALPINE) showed zanubrutinib had higher PFS and fewer atrial fibrillation events compared to ibrutinib in relapsed/refractory CLL.
- Can be used as frontline therapy in CLL, especially for patients with TP53 mutation or del(17p) where chemoimmunotherapy (like FCR) is less effective.
- Drug interactions: metabolized by CYP3A4 → avoid strong inhibitors/inducers.
Summary for oncology pharmacist:
Zanubrutinib is a next-gen BTK inhibitor with improved efficacy and safety over ibrutinib, making it an important option in CLL, WM, MCL, and MZL. In practice, it is now one of the preferred frontline agents for CLL in many guidelines.