FDA Approves Zanubrutinib for Previously Treated MCL

The FDA has granted an accelerated approval to zanubrutinib for the treatment of adult patients with mantle cell lymphoma who have received at least 1 prior therapy.

The FDA has granted an accelerated approval to zanubrutinib (Brukinsa) for the treatment of adult patients with mantle cell lymphoma (MCL) who have received at least 1 prior therapy.

“Clinical trials showed that 84% of patients saw tumor shrinkage with this therapy. For patients whose disease relapses or becomes refractory, secondary therapies may be successful in providing another remission, and today’s approval will provide patients with another treatment option,” Richard Pazdur, MD, director of the FDA’s Oncology Center of Excellence and acting director of the Office of Oncologic Diseases in the FDA’s Center for Drug Evaluation and Research, said in a statement about the approval for zanubrutinib.

The approval was based on findings from a single-arm trial of 86 patients with previously treated MCL who received the BTK inhibitor as well as an additional single-arm trial of 32 patients with MCL.

The first trial was a single-arm, open-label, multicenter phase II trial conducted in China that included patients with relapsed or refractory MCL who had received 1 to 4 prior therapies. Patients were given zanubrutinib 160 mg twice daily until disease progression or unacceptable toxicity. The primary end point of the study was objective response rate (ORR) by an independent review committee using PET-based imaging, with responses assessed according to the Lugano classification.2

Patients had a median age of 60.5 years, 52.3% had refractory disease and 47.7% had relapsed MCL. A total of 78 patients (90.7%) had stage III/IV disease and 72 (83.7%) were intermediate or high risk by the Mantle Cell Lymphoma International Prognostic Index Combined Biologic Index.

According to findings presented at the 2018 ASH Annual Meeting, the ORR was 83.5% with a complete response rate of 58.8% as the best response and partial responses in 24.7% among 85 evaluable patients. Patients with blastoid variant had an ORR of 75%.

The median PFS was not met as of the data cutoff after a median follow-up of 35.9 weeks, and the median duration of response was 19.5 months. As of data cutoff, 21 patients had discontinued treatment, 13 due to progressive disease and 6 due to adverse events (AEs).

Common treatment-emergent AEs (TEAEs) included decreased neutrophil count (31.4%), upper respiratory tract infection (29.1%), rash (29.1%), decreased platelet count (22.1%), and decreased white blood cell (WBC) count (17.4%). Grade ≥3 TEAEs reported in at least 2 patients included decreased neutrophil count (11.6%), lung infection (5.8%), anemia (4.7%), and decreased WBC count (3.5%).

There were 4 deaths in the trial; 1 due to infection, 1 due to pneumonia, 1 due to cerebral hemorrhage, and 1 because of a traffic accident. TEAEs of special interest included diarrhea (10.5%), hypertension (8.1%), and petechiae/purpura/contusion (4.7%).

The second trial demonstrated tumor shrinkage in 84% of patients and had a median response duration of 18.5 months.1

“Mantle cell lymphoma usually responds well to initial treatment, but eventually returns or stops responding, and the cancer cells continue to grow. This is a life-threatening condition,” Pazdur added in the statement.

The FDA also noted in its approval that patients treated with zanubrutinib should be monitored for hemorrhage, signs and symptoms of infection, cytopenias, and cardiac arrhythmias. Additionally, there is a risk of other malignancies, including skin cancers, related to treatment with zanubrutinib, so the use of sun protection is encouraged.

Previously this year the FDA had also granted the BTK inhibitor with a breakthrough therapy designation in the same setting and the agent has also received an orphan drug designation.


  1. FDA approves therapy to treat patients with relapsed and refractory mantle cell lymphoma supported by clinical trial results showing high response rate of tumor shrinkage. FDA website. https://bit.ly/376jQ4i. Published November 14, 2019. Accessed November 14, 2019.
  2. 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.