A Brukinsa regimen has delivered a large progression-free survival (PFS) benefit in what BeOne Medicines called a “new chemotherapy-free standard” in first-line mantle cell lymphoma.
The BTK inhibitor, combined with rituximab, reduced the risk of progression or death by 43% compared with bendamustine and rituximab (BR) in the phase 3 Mangrove study, BeOne announced Tuesday.
Overall survival (OS), a key secondary endpoint, remained immature but showed a “strong trend” in favor of the Brukinsa regimen, the company said.
The Mangrove study, also known as BGB-3111-306, is meant to serve as the confirmatory trial for Brukinsa’s accelerated approval in previously treated MCL. Granted in 2019, that FDA nod kicked off Brukinsa’s blockbuster journey. BeOne said it’s in discussions with regulatory authorities on planned submissions in 2026.
OS outcomes will likely be key in BeOne’s approval bid with the FDA. Previously, AbbVie and Johnson & Johnson withdrew Imbruvica’s MCL indication in the U.S. after the phase 3 Shine study showed a statistically significant reduction in the risk of disease progression or death, but a negative OS trend, for the addition of Imbruvica to bendamustine and rituximab.
In early 2025, the FDA greenlighted AstraZeneca’s rival BTK drug Calquence, used in tandem with bendamustine and rituximab, in first-line MCL patients who are ineligible for autologous stem cell transplant. In the phase 3 Echo study, the Calquence regimen cut the risk of disease progression or death by 27% versus bendamustine and rituximab. At the time of the PFS analysis, OS data remained immature but favored the Calquence regimen, with patient deaths reported in 32% of the Calquence arm versus 35% in the control arm.
Then, in July 2025, based on the phase 3 Triangle study conducted in Europe, J&J convinced the European Commission to approve Imbruvica as part of a multi-drug combination, which involves the R-CHOP combo for first-line MCL patients who would be eligible for an autologous stem cell transplant. In that study, Imbruvica plus chemoimmunotherapy with or without transplant significantly reduced the risk of death by 47.8% versus transplant and chemoimmunotherapy.
Now, without bendamustine and rituximab maintenance, Brukinsa plus rituximab have shown “unprecedented improvements” in PFS, “potentially redefining the treatment paradigm globally,” BeOne’s chief medical officer of hematology, Amit Agarwal, M.D., Ph.D., said in a June 30 statement.
“We believe it would be very meaningful for patients to be free from the burden of frequent infusions,” he added.
Sparing patients the toxicity burden of upfront chemotherapy could be beneficial in MCL, as the non-Hodgkin lymphoma subtype predominantly affects older adults, according to BeOne.
An approval in first-line MCL could help Brukinsa pull further ahead of Calquence in revenue as the two drugs eat away at Imbruvica’s market share. In the first quarter, Brukinsa global sales reached $1.1 billion, versus $923 million for Calquence.