Zanubrutinib/Rituximab Improves PFS in Frontline Mantle Cell Lymphoma

The addition of zanubrutinib (Brukinsa) to rituximab (Rituxan) produced superior progression-free survival (PFS) outcomes vs bendamustine (Treanda) plus rituximab (BR) for the frontline treatment of adult patients with mantle cell lymphoma (MCL) in the phase 3 MANGROVE trial (NCT04002297), according to a news release from the developer, BeOne Medicines.¹

Findings revealed that MANGROVE met its primary end point for PFS, with the investigational regimen showing a statistically significant and clinically meaningful improvement vs BR per independent review committee (IRC) assessment. Specifically, a 43% reduction in the risk of progression or death (HR, 0.57; 95% CI, 0.43-0.76; P <.0001) was observed with the zanubrutinib-based regimen vs BR.

Moreover, overall survival (OS), a key secondary end point, showed a strong trend in favor of the investigational regimen despite being immature at the time of the analysis. Additionally, the safety profile of zanubrutinib/rituximab was consistent with the known profiles of each agent in this MCL population, with no new signals identified.

According to the developers, the full results from the phase 3 trial will be shared at an upcoming medical meeting, with submissions to global regulatory authorities planned for the second half of 2026. They further noted that the trial was conducted to evaluate a chemotherapy-free regimen for patients with untreated MCL, noting toxicity risks carried by chemoimmunotherapy including myelosuppression, prolonged immune suppression, and heightened infection risk, which could be burdensome for older patients.

“For patients with newly diagnosed MCL, chemotherapy is currently the default. MANGROVE demonstrates for the first time that [zanubrutinib] plus rituximab, a chemotherapy-free regimen, can deliver unprecedented improvements in [PFS], potentially redefining the treatment paradigm globally,” Amit Agarwal, MD, PhD, chief medical officer of Hematology at BeOne Medicines, said in the news release.¹ “We believe it would be very meaningful for patients to be free from the burden of frequent infusions. This is what it means to state that [zanubrutinib] is foundational: another study where it anchors frontline therapy and extends its leadership across B-cell malignancies.”

A total of 510 patients across 176 sites in the phase 3 protocol were randomly assigned to receive intravenous rituximab at a dose of 375 mg/m² on day 1 of cycles 1 to 6 and either 160 mg of zanubrutinib given as two 80-mg capsules orally twice daily or bendamustine at a dose of 90 mg/m² on days 1 and 2 of cycles 1 to 6.² Following the initial treatment period, zanubrutinib was given as a monotherapy in the absence of disease progression or unacceptable toxicity.

The primary end point of the trial was PFS per IRC evaluation. OS, investigator-assessed PFS, overall response rate, duration of response, patient-reported outcomes, and safety were among the secondary end points.

Eligibility criteria for the MANGROVE trial included patients 70 years and older or between 60 and 69 years old with comorbidities precluding autologous stem cell transplantation, a histologically confirmed MCL diagnosis, no prior systemic treatments for MCL, and measurable disease by CT/MRI. Additional inclusion criteria were an ECOG performance status of 0 to 2, as well as adequate marrow and organ function.

Patients excluded from the trial protocol included those with known central nervous involvement, clinically significant cardiovascular disease, and a history of severe bleeding disorder. Moreover, those undergoing therapy for the aim of debulking prior to stem cell transplantation; those unable to swallow capsules or with disease impacting gastrointestinal function; those with active fungal, bacterial, and/or viral infections requiring systemic therapy; and those who require ongoing treatment with a CYP3A inhibitor or inducer were among those ineligible for trial enrollment.

References

1. BeOne Medicines announces positive phase 3 results for BRUKINSA in frontline mantle cell lymphoma. News release. BeOne Medicines Ltd. June 30, 2026. Accessed July 1, 2026. https://tinyurl.com/t2mwvdn2
2. A study to investigate the efficacy of zanubrutinib plus rituximab compared with bendamustine plus rituximab in adults with previously untreated mantle cell lymphoma who are ineligible for stem cell transplantation (MANGROVE). ClinicalTrials.gov. Updated May 18, 2026. Accessed July 1, 2026. https://tinyurl.com/48c2pck5