Zanubrutinib Receives FDA Approval for Treatment-Resistant and Recurrent Mantle Cell Lymphoma

For treatment-resistant or relapsed (recurrent) mantle cell lymphoma , developed for treatment and demonstrating high levels of tumor regression response in clinical studies, zanubrutinib (Brukinsa) , a capsule-form drug, received accelerated approval on 14 November 2019 from the US Food and Drug Administration (FDA).

Mantle cell lymphoma generally responds well to initial treatment, but then stops responding and cancer cells proliferate again. In clinical studies of this drug developed for this life-threatening condition, in 84% of patients, tumor regression was observed. In patients whose disease is relapsed (recurrent) or refractory (treatment-resistant), secondary treatments may provide another remission (period of recovery).

The single-arm clinical study of Brukinsa evaluated 86 patients who had received at least one previous treatment. The study observed how many patients experienced complete or partial tumor shrinkage after Brukinsa treatment. Tumor shrinkage was observed in 84% of patients, with a median response duration of 19,5 months (median duration of response—the time from the initial response until disease progression or relapse). This observation was supported by another single-arm study of 32 patients. In this supporting study, tumor shrinkage was also observed in 84% of patients, with a median response duration of 18,5 months.

Common side effects include decreased white blood cell (leukocyte) counts (leukocytes fight infections in our body), decreased platelet counts (blood cells that initiate and enable clotting), upper respiratory tract infections, decreased hemoglobin (the oxygen-carrying protein in red blood cells), rash, bruising, diarrhea and cough. During treatment, patients should be monitored for bleeding risk, signs and symptoms of infection, cytopenia (reduced blood cell counts) and cardiac arrhythmias (irregular heartbeat). Protection against sunlight is also recommended because some other malignancies, including skin cancer, may increase. Patients of reproductive potential and their partners should also be told to use effective contraception during treatment. Pregnant and breastfeeding patients should not use this drug.

What Is Mantle Cell Lymphoma?

Mantle cell lymphoma is a subtype of mature B-cell non-Hodgkin lymphoma (NHL), accounting for 3-10% of all non-Hodgkin lymphomas. Its course varies but is generally aggressive. By the time mantle cell lymphoma is diagnosed, it has usually spread to lymph nodes, bone marrow and other organs. In relapsed lymphoma, disease progresses again after a period of remission or stability, whereas in refractory lymphoma it never responds to treatment or responds only briefly. Median overall survival in mantle cell lymphoma with intensive treatment is 8-10 years.

• Related topic: What Is the Difference Between Leukemia and Lymphoma?

How Does Zanubrutinib Work?

Zanubrutinib is an inhibitor developed against the Bruton Tyrosine Kinase (BTK) enzyme. BTK plays a role in B cells , in the regulation of proliferation, as part of a cellular signaling pathwayand its receptor . Inhibiting BTK can prevent uncontrolled B-cell proliferation in B-cell malignancies. Zanubrutinib binds covalently to BTK, leading to irreversible inhibition of the enzyme.