Zanubrutinib Approved for Relapsed/Refractory Marginal Zone Lymphoma

Marginal zone lymphoma cells.

The FDA has granted accelerated approval to zanubrutinib (Brukinsa®, BeiGene) for the treatment of patients with relapsed/refractory marginal zone lymphoma (MZL) who have received at least one anti–CD20-based regimen.

“Marginal zone lymphoma is rare and heterogeneous, and it has been difficult to define optimal therapeutic strategies,” wrote Stephen Opat, FRACP, FRCPA, MBBS, Director of Clinical Hematology at Monash Health in Australia, and colleagues, in their publication of the initial results of the MAGNOLIA trial (NCT03846427), one of the two trials on which the approval was based. “Like other indolent non-Hodgkin lymphomas, advanced stage disease is considered incurable, with most patients experiencing a continuing pattern of relapse and remission.”

MAGNOLIA, a single-arm multicenter phase 2 trial, evaluated 66 patients with relapsed/refractory MZL who had received at least one CD20-directed regimen. Patients received 160 mg zanubrutinib twice daily until disease progression or unacceptable toxicity. The primary end point was overall response rate, with secondary end points of duration of response, progression-free survival, and safety. Zanubrutinib produced an overall response rate of 56% and a complete response rate of 20%, based on computed tomography (CT) assessment; on positron emission tomography (PET)/CT assessment, the overall response rate and complete response rate were 67% and 26%, respectively. At 12 months, 85% of responders remained in remission. At a median follow-up of 8.2 months, the median duration of response had not been reached.

Efficacy was also assessed in BGB-3111-AU-003 (NCT02343120), a phase 1/2 trial of patients with B-cell malignancies, including 20 patients with MZL. In this trial, zanubrutinib produced an overall response rate of 80% and a complete response rate of 20%, based on CT assessment. At 12 months, 72% of responders remained in remission; at a median follow-up of 31.4 months, the median duration of response had not been reached.

Adverse events occurring in at least 30% of patients receiving zanubrutinib in both trials included decreased neutrophil count, upper respiratory tract infection, decreased platelet count, hemorrhage, decreased lymphocyte count, rash, and musculoskeletal pain.

The recommended dose of zanubrutinib is 160 mg twice daily or 320 mg once daily, taken orally with or without food. The dose may be adjusted for patients with severe hepatic impairment or certain drug interactions and for those experiencing adverse events.

For More Information

Opat S, Tedeschi A, Linton K, et al (2020). Efficacy and safety of zanubrutinib in patients with relapsed/refractory marginal zone lymphoma: initial results of the MAGNOLIA (BGB-3111-214) trial. Presented at: 62nd ASH Annual Meeting and Exposition. Abstract 339.

Tam CS, Trotman J, Opat S, et al (2019). Phase 1 study of the selective BTK inhibitor zanubrutinib in B-cell malignancies and safety and efficacy evaluation in CLL. Blood, 134(11):851-859. DOI:10.1182/blood.2019001160 (2021). Study of zanubrutinib (BGB-3111) in participants with marginal zone lymphoma (MAGNOLIA). NLM Identifier: NCT03846427. (2021). Study of the safety and pharmacokinetics of BGB-3111 in subjects with B-cell lymphoid malignancies. NLM identifier: NCT02343120.

Brukinsa® (zanubrutinib) prescribing information (2021). BeiGene. Available at:

BeiGene (2021). U.S. FDA grants Brukinsa® (zanubrutinib) accelerated approval in relapsed or refractory marginal zone lymphoma. Available at:

Image courtesy of Librepath. Licensded under CC BY-SA 3.0

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