Written by: Kayla Randle, PharmD, BCPS, BCOP, Kaiser Permanente Georgia Oncology
The purpose of this PQI is to identify differentiating characteristics which would indicate zanubrutinib (Brukinsa®) as a preferred treatment option in Mantle Cell Lymphoma as well as discussing key counseling and monitoring criteria to improve patient outcomes.
Zanubrutinib is a potent, highly specific, and irreversible inhibitor of Bruton’s tyrosine kinase (BTK) and is an investigational treatment for B-cell malignancies including chronic lymphocytic leukemia (CLL), mantle cell lymphoma (MCL), and Waldenström macroglobulinemia (WM)1. Zanubrutinib received FDA breakthrough therapy designation for the treatment of adult patients with MCL following at least one prior therapy on November 14, 2019 based on data from a phase I and a phase II trial. 3,5
Zanubrutinib has shown greater selectivity for BTK with fewer off-target receptor interactions compared to the currently approved agents in the class.2 Potential side effects seen with BTK inhibitors are likely related to off-target interaction with other receptors including epidermal growth factor receptor (EGFR) and interleukin-2-inducible T-cell kinase (ITK). 3-5 A phase I/II trial evaluated zanubrutinib 160 mg twice daily or 320 mg once daily in 144 patients with various B-cell malignancies. Safety analysis in these patients showed a less than 2% incidence of both Atrial fibrillation (Afib) and major hemorrhage which are potential grade 3/4 adverse effects seen with other BTK inhibitors.5
Upon receipt of an order for zanubrutinib:
- Ensure patient is appropriate candidate for zanubrutinib based on indication
- Patient comorbidities may make zanubrutinib a safer option (i.e., history of Afib, recent hemorrhage, hypertension, concomitant PPI or H2R antagonists)
- Dose of zanubrutinib is either 160 mg twice daily or 320 mg once daily based on patient preference/ability to adhere to twice daily medication
- Reduce zanubrutinib dose accordingly if co-administered with:
- Strong CYP3A inhibitor – 80 mg once daily
- Moderate CYP3A inhibitor – 80 mg twice daily
- Moderate or strong CPY3A inducer – avoid concomitant use
- Reduce zanubrutinib dose to 80 mg twice daily in patients with severe hepatic impairment (Child-Pugh Class C)
- Consider prophylaxis for herpes simplex virus, Pneumocystis jirovecii pneumonia, and other infections according to standard of care in patients at increase risk for infections. Grade 3 or higher infections occurred overall in 23% of patients on zanubrutinib with pneumonia being the most common infection.
- Verify monitoring parameters:
- CBC with differential, hepatic function
- Signs/symptoms of Afib/flutter, bleeding, or infections including opportunistic infections
Patient Centered Activities:
- Provide Oral Chemotherapy Education (OCE) sheet
- Counsel to administer orally
- Review once a day vs. twice a day dosing
- Review baseline labs and chronic medications – dose adjustment needed with concomitant CYP3A4 inhibitors
- Proper sign/symptom monitoring
- Evaluate if patients have missed any doses between cycles to determine if interventions are needed such as reminders, calendars, pill box, etc.
- See full prescribing information for dose modifications with Grade 3 or worse adverse effects
- BeiGene Presents Updated Head to Head Results from Phase 3 Trial of Zanubrutinib vs. Ibrutinib in Patients with Waldenström’s Macroglobulinemia at the 2020 American Society of Clinical Oncology (ASCO) Virtual Scientific Program [news release]: BeiGene. Published May 29, 2020. http://ir.beigene.com/news-releases/news-release-details/beigene-presents-updated-head-head-results-phase-3-trial?loc=US
- Flinsenberg TWH, et al. Differential effects of BTK inhibitors ibrutinib and zanubrutinib on NK cell effector function in patients with mantle cell lymphoma. Haematologica. June 6, 2019. Epub ahead of print.
- Song Y, Zhou K, Zou D, et al. Safety and activity of the investigational Bruton tyrosine kinase inhibitor zanubrutinib (BGB-3111) in patients with mantle cell lymphoma from a phase 2 trial. In: Proceedings from the 2018 ASH Annual Meeting; December 1-4, 2018; San Diego, CA. Abstract 148.
- Tam CS, et al. A head-to-head Phase III study comparing zanubrutinib versus ibrutinib in patients with Waldenström macroglobulinemia.Future Oncol. 2018 Sep;14(22):2229-2237.
- Tam CS, et al. Phase I study of selective BTK inhibitor zanubrutinib in B-cell malignancies and safety and efficacy evaluation in CLL. Blood. July 24, 2019. Epub ahead of print.
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