Brukinsa From BeiGene, Ltd

The FDA has approved zanubrutinib (Brukinsa, BeiGene) for the treatment of adults with Waldenström macroglobulinemia (WM).¹

Zanubrutinib also received approval for adults with relapsed or refractory marginal zone lymphoma (MZL) who have received at least 1 anti-CD20-based regimen. The MZL indication was approved under accelerated approval based on overall response rate, and its continued approval may be contingent upon description and verification of clinical benefit in a confirmatory trial.²

Pharmacology and Pharmacokinetics

Zanubrutinib is a small molecule inhibitor of Bruton tyrosine kinase. After oral administration, the median time to maximum concentration is 2 hours, and the elimination half-life is approximately 2 to 4 hours. Zanubrutinib is metabolized primarily by cytochrome P450 (CYP) 3A.²

Dosage and Administration

The recommended dose of zanubrutinib is 160 mg orally twice daily or 320 mg orally once daily. Patients with severe hepatic impairment should use 80 mg orally twice daily. The dose for patients who are concomitantly using a strong CYP3A inhibitor is 80 mg orally once daily. Patients concomitantly using a moderate CYP3A inhibitor should use 80 mg orally twice daily. Zanubrutinib should not be coadministered with a moderate or strong CYP3A inducer. Discontinuation, dose reduction, or interruption of treatment may be required if a grade 3 or higher adverse reaction occurs. The medication should be swallowed whole with water, with or without food.²

Clinical Trials

The efficacy of zanubrutinib in WM was evaluated in an active control, open-label, randomized trial (ASPEN; NCT03053440). Participants were randomized 1:1 to receive zanubrutinib 160 mg twice daily or ibrutinib 420 mg once daily until disease progression or unacceptable toxicity occurred. The major efficacy outcome was the response rate, which was 78% with zanubrutinib and 78% with ibrutinib. An additional efficacy outcome measure was duration of response, which at 12 months was 94% with zanubrutinib and 88% with ibrutinib.^2,3

The efficacy of zanubrutinib in MZL was assessed in a multicenter, open-label, single-arm trial of 66 patients who had received at least 1 prior anti–CD20-based therapy. Participants received zanubrutinib 160 mg orally twice daily until disease progression or unacceptable toxicity occurred. Efficacy was based on overall response rate (ORR) and the duration of response. The ORR based on CT scan assessment was 56% with a complete response (CR) rate of 20%. The ORR based on prioritizing positron emission tomography–CT scan was 67%, with a CR rate of 26%. The duration of response was not reached at the median follow-up of 8.3 months. At 12 months, 85% of the responders were still in remission.

Zanubrutinib was also evaluated in a multicenter, open-label, single-arm trial (NCT02343120) of 20 patients with previously treated MZL. Participants received zanubrutinib 160 mg orally twice daily or 320 mg once daily. The ORR based on CT scan assessment was 80%, with a CR rate of 20%. The median duration of response was not reached at the median follow-up time of 31.4 months. At 12 months, 72% of the responders were still in remission.^1,2

Contraindications, Warnings, and Precautions

There are no contraindications to treatment with zanubrutinib. Patients using zanubrutinib should be monitored for bleeding, and the medication should be discontinued if any grade of intracranial hemorrhage occurs. Fatal and serious infections have occurred during treatment with zanubrutinib. Because grade 3 or 4 cytopenias have occurred in patients using zanubrutinib monotherapy, complete blood counts should be monitored regularly during treatment. Second primary malignancies, including nonskin carcinoma, have occurred in patients taking zanubrutinib. Patients should be counseled to use sun protection during treatment. Atrial fibrillation and atrial flutter have been reported in patients receiving zanubrutinib monotherapy. Because zanubrutinib can cause fetal harm, both men and women should use effective contraception during treatment and for 1 week after the last dose. Women should not breastfeed while using zanubrutinib.

The most common adverse reactions are decreased lymphocyte count, decreased neutrophil count, decreased platelet count, hemorrhage, musculoskeletal pain, rash, and upper-respiratory tract infection.³

Monica Holmberg, PharmD, BCPS, is a pharmacist and Pharmacy Times contributor.

REFERENCES

1. U.S. FDA grants Brukinsa (zanubrutinib) approval in Waldenström’s macroglobulinemia. News release. BeiGene, Ltd; September 1, 2021. Accessed December 2, 2021. https://ir.beigene.com/news-details/?id=802fb825-acb1-455d-b916-c95068817a9d
2. U.S. FDA grants Brukinsa (zanubrutinib) accelerated approval in relapsed or refractory marginal zone lymphoma. News release. BeiGene, Ltd; September 15, 2021. December 2, 2021. https://ir.beigene.com/news-details/?id=0d5b56bb-d6cd-4606-a9bd-f49e85bb113b
3. Brukinsa. Prescribing information. BeiGene, Ltd; 2021. Accessed December 2, 2021. https://www.brukinsa.com/prescribing-information.pdf