Zanabrutinib Adverse Event Profile

Hematologic Adverse Events

• The National Comprehensive Cancer Network recommends monitoring for neutropenia, as any grade neutropenia occurs in 29% of patients, and grade ≥3 neutropenia occurs in 20-23% of patients, compared to 13% and 8% with ibrutinib, respectively 1, 2
• A larger proportion of patients require granulocyte colony-stimulating factor support compared to ibrutinib 1, 2

Cardiovascular Adverse Events

• Zanabrutinib has a significantly lower rate of atrial fibrillation, occurring in only 4% of patients, compared to 17% with ibrutinib, with grade ≥3 cases in 1.9% 1, 2, 3
• Hypertension occurs in 3-5% of patients, with grade ≥3 in 2-3% 4

Bleeding Events

• The overall bleeding risk is 26-39% for any grade, and 2% for grade ≥3 4
• Avoid concomitant warfarin use, and carefully evaluate the benefit-risk in patients requiring anticoagulation 4
• Hold zanubrutinib 3-7 days before and after surgical procedures 5

Gastrointestinal Adverse Events

• Nausea occurs in variable frequencies 5
• Gastrointestinal adverse events occur at lower rates than with ibrutinib 1, 2

Other Common Adverse Events

• Fatigue occurs in 10-21% of patients 4, 5

Key Clinical Pitfalls to Avoid

• Do not overlook neutropenia monitoring, as zanabrutinib has higher neutropenia rates requiring more vigilant CBC monitoring and potential G-CSF support 1, 2
• Do not assume all BTK inhibitors have equivalent cardiac toxicity, as zanabrutinib's 4-fold lower atrial fibrillation rate makes it preferable in patients with cardiac risk factors 1, 2, 3
• Do not combine zanabrutinib with warfarin, and use alternative anticoagulation strategies if needed 4