On September 14, 2021, the Bruton’s tyrosine kinase inhibitor zanubrutinib was granted accelerated approval for adults with relapsed or refractory marginal zone lymphoma (MZL) who have had at least one prior anti-CD20–based regimen.1
Supporting Efficacy Data
Approval was based on findings in the multicenter trials BGB-3111-214 (ClinicalTrials.gov identifier NCT03846427), which evaluated 66 patients with at least one prior anti-CD20–based therapy, and BGB-3111-AU-003 (NCT02343120), which included 20 patients with previously treated MZL.1 Zanubrutinib was administered orally at 160 mg twice daily or 320 mg once daily.
On independent review committee assessment, using the 2014 computed tomography–based Lugano criteria, objective response was observed in 37 patients (56%, 95% confidence interval [CI] = 43%–68%) in BGB-3111-214, with a complete response in 13 (20%), and in 16 patients (80%, 95% CI = 56%–94%) in BGB-3111-AU-003, with a complete response in 4 (20%). The median time to response was 2.9 months (range = 1.8–11.1 months) and 2.9 months (range = 2.6-–3.1 months) in the two studies. The median duration of response was not reached (95% CI = not estimable to not estimable) and not reached (95% CI = 8.4 months to not estimable) in the two trials; estimated rates of responses maintained at 1 year were 85% and 72%.
How It Is Used
The recommended zanubrutinib dosage is 160 mg twice daily or 320 mg once daily until disease progression or unacceptable toxicity. The recommended dose for patients with severe hepatic impairment is 80 mg twice daily.
Product labeling provides instructions on dosage modification, including dose reduction, for hematologic toxicities and grade 3 or 4 nonhematologic toxicities. Labeling provides information on concomitant use with moderate and strong CYP3A inhibitors and moderate or strong CYP3A inducers.
Among 88 patients receiving zanubrutinib in the BGB-3111-214 and BGB-3111-AU-003 trials, the most common adverse events of any grade were musculoskeletal pain (27%), upper respiratory tract infection (26%), diarrhea (25%), bruising (24%), hemorrhage (23%), rash (21%), and fatigue (21%). The most common grade 3 or 4 adverse events included pneumonia (6%), upper respiratory tract infection (3.4%), and diarrhea (3.4%). The most common grade 3 or 4 laboratory abnormalities were neutropenia (15%), thrombocytopenia (10%), and lymphopenia (8%).
Serious adverse events occurred in 40% of patients, most commonly pyrexia (8%) and pneumonia (7%). Adverse events led to treatment discontinuation in 6% of patients. Fatal adverse events occurred in two patients, due to myocardial infarction and COVID-19–related death.
Zanubrutinib has warnings/precautions for hemorrhage, infections, cytopenias, second primary malignancies (including skin cancers), cardiac arrhythmia, and embryofetal toxicity. Patients should be advised not to breastfeed while receiving zanubrutinib.
1. Brukinsa (zanubrutinib) capsules prescribing information, BeiGene, Ltd., September 2021. Available at https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/213217s005lbl.pdf. Accessed October 4, 2021.