What is the recommended use and dosage of Zanobrutinib (Bruton's tyrosine kinase inhibitor) for patients with mantle cell lymphoma or chronic lymphocytic leukemia?

Zanubrutinib Treatment Recommendations for MCL and CLL

Zanubrutinib is recommended at a dose of 160 mg twice daily orally for patients with relapsed/refractory mantle cell lymphoma (MCL) and chronic lymphocytic leukemia (CLL), and is considered a preferred category 1 treatment option due to its high efficacy and favorable safety profile compared to other BTK inhibitors. 1

Dosing and Administration

• Standard dose: 160 mg twice daily orally
• Administration: Continuous dosing until disease progression or unacceptable toxicity
• No dose adjustments needed for most patients

Efficacy in Mantle Cell Lymphoma

Zanubrutinib has demonstrated impressive efficacy in relapsed/refractory MCL:

• Overall response rate (ORR) of 83.7% with 77.9% complete response rate in long-term follow-up 2
• Median progression-free survival (PFS) of 33.0 months 2
• 36-month PFS and overall survival rates of 47.6% and 74.8%, respectively 2
• Durable responses with median duration of response not reached after 35.3 months of follow-up 2

Efficacy in Chronic Lymphocytic Leukemia

In CLL, zanubrutinib has shown superior efficacy compared to standard treatments:

• Superior efficacy compared to bendamustine-rituximab in the SEQUOIA trial with a PFS hazard ratio of 0.42 (p<0.0001) 1
• Particularly beneficial for patients with high-risk features 1

Safety Profile and Advantages

Zanubrutinib offers significant safety advantages over first-generation BTK inhibitors:

• Reduced cardiac toxicity with lower incidence of atrial fibrillation (4% vs 17% with ibrutinib) 1

• Most common adverse events are typically grade 1-2 and include:

  • Neutropenia (reported in up to 46.5% of patients) 2
  • Upper respiratory tract infection (38.4%) 2
  • Rash (36%) 2
  • Decreased white blood cell count (33.7%) 2
  • Decreased platelet count (32.6%) 2
  • Diarrhea (reported in 43.8% of patients in some studies) 3

• Rates of infection, neutropenia, and bleeding are highest in the first 6 months of therapy and decrease thereafter 2

Patient Selection

Zanubrutinib is particularly beneficial for:

• Patients with cardiac comorbidities who may not tolerate ibrutinib's cardiovascular side effects 1
• Patients with high-risk CLL features 1
• Patients who experienced toxicity with other BTK inhibitors 1

Management of Common Adverse Events

• Grade 3-4 neutropenia: Consider G-CSF support 1
• Infections: Appropriate antimicrobial therapy; prophylaxis may be considered in high-risk patients 1
• Bleeding events: Temporary interruption for procedures or active bleeding 1

Clinical Pearls and Pitfalls

• Monitor complete blood counts regularly, especially during the first 6 months of treatment when cytopenias are most common
• Unlike ibrutinib, zanubrutinib has not been associated with atrial fibrillation in clinical trials, making it a preferred option for patients with cardiac risk factors 2
• No cases of tumor lysis syndrome were reported in clinical trials, but monitoring is still recommended when initiating therapy in high-risk patients 2
• Be vigilant for infections, which can be serious (grade ≥3 infections reported in 18.8% of patients) 3