FDA grants Priority Review to Brukinsa plus rituximab for previously untreated mantle cell lymphoma
The US Food and Drug Administration (FDA) has accepted BeOne Medicines’ supplemental New Drug Application for Brukinsa (zanubrutinib) in combination with rituximab, granting it Priority Review. The application covers adults with previously untreated mantle cell lymphoma (MCL).
If approved, the combination would become the first and only chemotherapy-free, BTK inhibitor-based regimen for this group of patients. Chemoimmunotherapy is currently the standard approach.
MANGROVE results
The application is based on MANGROVE, a global, randomised, open-label Phase 3 trial. It enrolled 510 adults with previously untreated MCL and compared Brukinsa plus rituximab with bendamustine plus rituximab (BR).
Brukinsa plus rituximab cut the risk of disease progression or death by 43% compared with BR (HR 0.57; 95% CI 0.43–0.76; p<0.0001). This met the trial’s primary endpoint of progression-free survival, as assessed by an independent review committee. The safety profile matched the known profiles of both medicines, and no new safety signals were seen.
In the experimental arm, patients took Brukinsa 160 mg orally twice daily alongside rituximab during the initial treatment period, then continued on Brukinsa alone until disease progression or intolerance. Patients in the control arm received six cycles of BR. Overall survival is a key secondary endpoint.
Full results will be presented at the Plenary Scientific Session of the 68th American Society of Hematology (ASH) Annual Meeting on 13 December 2026.
Amit Agarwal, MD, PhD, Chief Medical Officer, Hematology at BeOne Medicines, said: “In newly diagnosed mantle cell lymphoma, chemoimmunotherapy remains a mainstay of frontline treatment despite the toxicity burden it carries. The FDA’s acceptance of our application brings us closer to a chemotherapy-free, BRUKINSA-based option that significantly reduces the risk of disease progression or death.”
Regulatory picture
Applications for Brukinsa in MCL have also been submitted to the European Medicines Agency and accepted by China’s National Medical Products Administration.
In the US, Brukinsa is already approved for relapsed or refractory MCL. It is also approved for chronic lymphocytic leukaemia/small lymphocytic lymphoma, Waldenström’s macroglobulinaemia, relapsed or refractory marginal zone lymphoma, and relapsed or refractory follicular lymphoma.
About Brukinsa
Brukinsa is a next-generation Bruton tyrosine kinase (BTK) inhibitor designed for complete and sustained BTK inhibition. It is approved in more than 80 markets and has been used to treat over 310,000 patients worldwide.
Serious adverse reactions, including fatal events, have occurred with Brukinsa. These include haemorrhage, infections, cytopenias, second primary malignancies, cardiac arrhythmias and hepatotoxicity.
Source: BeOne Medicines
The filing is backed by Phase 3 MANGROVE data showing a 43% reduction in the risk of progression or death compared with bendamustine plus rituximab.
