Brukinsa/rituximab cuts progression risk 43% in mantle cell lymphoma

Brukinsa (zanubrutinib) plus rituximab reduced the risk of progression or death by 43% in adult patients with previously untreated mantle cell lymphoma (MCL) in a phase 3 trial that compared the combination with bendamustine plus rituximab.

Mantle cell lymphoma is an aggressive form of non-Hodgkin lymphoma (NHL), representing roughly 5% of non-Hodgkin lymphoma cases. Mantle cell lymphomas are more common in men and in older adults. In mantle cell lymphoma, relapse after initial treatment is common. Standard treatment for mantle cell lymphoma has been chemoimmunotherapy, such as bendamustine plus rituximab.

“For patients with newly diagnosed MCL, chemotherapy is currently the default," said Amit Agarwal, M.D., Ph.D., chief medical officer, hematology, at BeOne Medicines, which developed and markets Brukinsa. “MANGROVE demonstrates for the first time that Brukinsa plus rituximab, a chemotherapy-free regimen, can deliver unprecedented improvements in progression-free survival, potentially redefining the treatment paradigm globally.”

Brukinsa is an oral medication and an inhibitor of Bruton’s tyrosine kinase (BTK). BTK is a signaling molecule of the B-cell antigen receptor and cytokine receptor pathways. In nonclinical studies, Brukinsa inhibited growth of malignant B cells and reduced tumor growth.

Brukinsa is indicated for the treatment of several cancers, including mantle cell lymphoma, marginal zone lymphoma, chronic lymphocytic leukemia or small lymphocytic lymphoma, follicular lymphoma, and Waldenström’s macroglobulinemia. The wholesale acquisition cost, or list price, of Brukinsa is $16,673 per bottle, before discounts or rebates, according to a company spokesperson. Patients with commercial insurance may be eligible for a $0 copay for Brukinsa, with an annual limit of $25,000.

MANGROVE is a randomized trial to evaluate a BTK inhibitor therapy with rituximab, a monoclonal antibody, compared with standard chemoimmunotherapy in patients with mantle cell lymphoma. The trial enrolled 510 patients across 176 sites worldwide. In the experimental arm, patients received Brukinsa at 160 mg orally twice daily plus rituximab during the initial treatment period, followed by Brukinsa monotherapy until disease progression or intolerance. In the control arm, patients received bendamustine plus rituximab for six cycles.

The trial met the primary endpoint of progression-free survival, demonstrating a clinically meaningful improvement for Brukinsa plus rituximab compared with bendamustine plus rituximab. This Brukinsa-based regimen led to a 43% reduction in the risk of progression or death.

The safety profile of Brukinsa plus rituximab was consistent with the known safety profile of both medicines, with no new safety signals identified. In a pooled analysis of 1,729 patients, the most common adverse reactions, including laboratory abnormalities, in patients who received Brukinsa were neutrophil count decreased (51%), platelet count decreased (41%), upper respiratory tract infection (38%), hemorrhage (32%), and musculoskeletal pain (31%).

Full results from Brukinsa will be shared at an upcoming medical meeting. BeOne in discussions with global regulatory authorities with planned submissions in the second half of 2026.