Zanubrutinib — Drug Monograph
Brand names: Brukinsa
Drug class: BTK Inhibitor
Mechanism of Action
Third-generation, highly selective, irreversible covalent BTK inhibitor. Designed to maximize BTK occupancy throughout the dosing interval with a pharmacokinetic profile that minimizes off-target effects. Binds covalently to Cys481 in the BTK active site. Like acalabrutinib, zanubrutinib has minimal off-target activity against EGFR, ITK, and TEC. Achieves greater and more sustained BTK occupancy in lymph nodes, peripheral blood, and bone marrow compared to ibrutinib.
FDA Indications
- Chronic lymphocytic leukemia (CLL) / small lymphocytic lymphoma (SLL) — first-line and relapsed/refractory
- Mantle cell lymphoma (MCL) — relapsed/refractory
- Waldenström macroglobulinemia (WM) — any line
- Marginal zone lymphoma (MZL) — relapsed/refractory after ≥1 anti-CD20 therapy
- Relapsed/refractory follicular lymphoma (FL) — in combination with obinutuzumab
Common Side Effects
- Bruising/contusion
- Diarrhea
- Fatigue
- Neutropenia
- Upper respiratory tract infection
- Musculoskeletal pain
- Rash
- Cough
Clinical Pearl
ALPINE trial (zanubrutinib vs. ibrutinib in R/R CLL) demonstrated superior PFS (HR 0.65) and significantly lower AF rates (5.2% vs. 13.3%) with zanubrutinib — the first head-to-head trial showing BTK inhibitor superiority in CLL. Zanubrutinib does NOT have the PPI interaction problem seen with acalabrutinib (no capsule pH-dependent absorption), making it preferred in patients on gastric acid suppression therapy.
Related Therapies & Mechanisms
- Acalabrutinib (Calquence) — BTK Inhibitor · Lymphoma
- Pirtobrutinib (Jaypirca) — BTK Inhibitor · Lymphoma
- Bendamustine (Treanda) — Lymphoma
- Brexucabtagene autoleucel (Tecartus) — Lymphoma