The U.S. Food and Drug Administration (FDA) has granted accelerated approval of zanubrutinib (Brukinsa) to treat adult patients with relapsed or refractory (R/R) marginal zone lymphoma (MZL) who have received at least one anti-CD20-based regimen.

MZL is a group of indolent mature B-cell non-Hodgkin lymphomas (NHLs) that are generally considered a chronic and incurable disease. With an annual incidence of approximately 8,200 newly diagnosed patients in the United States, MZL is the third most common B-cell NHL, accounting for approximately 10% of all NHL cases.

The FDA’s Accelerated Approval process is for medications that treat serious conditions that fill an unmet medical need and based on  preliminary results that are reasonably likely to predict a clinical benefit to patients. Since zanubrutinib was approved on a phase II study, it is likely that further clinical trials to verify and describe zanubrutinib’s clinical benefit – either by the FDA and/or by insurance companies – will be necessary.

The accelerated approval was largely based on the Phase 2 MAGNOLIA trial (NCT03846427) in patients with R/R MZL who received at least one anti-CD20-based regimen, a total of 66 patients were evaluated, including 26 with extranodal subtype, 26 with nodal subtype, 12 with splenic subtype, and four with unknown subtype. The study observed an overall response rate (ORR) of 56% and complete response (CR) rate of 20% using CT scans. With PET-CT scan, the ORR was 67% and the CR rate of 26%. Further, median duration of response was not reached at the median follow-up time of 8.3 months and 85% of responders were still in remission at 12 months.

Common adverse reactions were decreased neutrophil count, upper respiratory tract infection, decreased platelet count, hemorrhage, decreased lymphocyte count, rash, and musculoskeletal pain.

Zanubrutinib is a Bruton’s tyrosine kinase (BTK) inhibitor. In a press release, Stephen Opat, FRACP, FRCPA, MBBS, at Monash University, and lead principal investigator of the MAGNOLIA trial stated, ““BTK plays a critical role in B-cell receptor signaling, a driver in the development of marginal zone lymphoma. In the MAGNOLIA trial, Brukinsa demonstrated impressive overall response and complete remission rates, with responses observed in all MZL subtypes. In addition, this next-generation BTK inhibitor was well-tolerated in these patients, with low rate of discontinuation due to adverse reactions. We are optimistic that Brukinsa  will bring clinically meaningful benefit to patients with relapsed or refractory marginal zone lymphoma.”

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