Frontline zanubrutinib plus rituximab demonstrated significant efficacy compared with SOC chemoimmunotherapy in patients with mantle cell lymphoma.
Zanubrutinib (Brukinsa) in combination with rituximab (Rituxan) generated statistically significant improvements in progression-free survival (PFS) over standard-of-care (SOC) chemoimmunotherapy in the first-line setting in patients with mantle cell lymphoma (MCL), according to data from the phase 3 MANGROVE trial (NCT04002297).1
Patients who received zanubrutinib plus rituximab experienced a 43% reduction in the risk of disease progression or death compared with those who received SOC chemoimmunotherapy (HR, 0.57; 95% CI, 0.43-0.76; P < .0001). Moreover, overall survival (OS) data, although immature at the time of this analysis, indicated trends in favor of the zanubrutinib-based combination. The investigators noted that OS data will be evaluated as part of the trial’s final analysis.
Full results from MANGROVE are planned for presentation at a future medical meeting. BeOne Medicines, the drug’s developer, also plans to submit the MANGROVE data to global regulatory authorities for potential regulatory approval in the second half of 2026.
“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 a news release. “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.”
Zanubrutinib was previously approved by the FDA in
Investigators of the trial sought to evaluate the efficacy of zanubrutinib plus rituximab, a chemotherapy-free regimen, vs SOC chemoimmunotherapy in the frontline setting for MCL.
Frontline Zanubrutinib Plus Rituximab Yields PFS Benefit Over SOC Chemoimmunotherapy in MCL: MANGROVE Highlights
The randomized, global, open-label study enrolled patients aged at least 70 years at the time of informed consent or at least 60 years with comorbidities precluding autologous stem cell transplantation.4 Patients also needed to have a histologically confirmed diagnosis of MCL, have received no prior systemic lines of therapy for MCL, have an ECOG performance status of 2 or less, and have adequate bone marrow and organ function.
If patients had known central nervous system involvement by lymphoma, clinically significant cardiovascular disease, a history of severe bleeding disorders, or active fungal, bacterial, or viral infections that required systemic therapy, they were not included in the trial.
The trial enrolled 510 patients. Patients in the zanubrutinib arm received zanubrutinib 160 mg twice daily alongside rituximab during the initial treatment period, followed by zanubrutinib monotherapy until disease progression or treatment intolerance.1 Patients in the SOC chemoimmunotherapy arm received 6 cycles of bendamustine plus rituximab.
The trial’s primary end point is PFS assessed by independent review committee, and OS is the key secondary end point. Investigator-assessed PFS, overall response rate, safety, duration of response, and patient-reported outcomes also serve as secondary end points.
Common adverse effects (AEs) experienced by patients in the pooled safety population of the trial who received zanubrutinib (n = 1729) were decreased neutrophil count (51%), decreased platelet count (41%), upper respiratory tract infection (38%), hemorrhage (32%), and musculoskeletal pain (31%).
Investigators also noted that serious AEs, such as hemorrhage, infections, second primary malignancies, cardiac arrhythmias, cytopenias, and hepatotoxicity, have occurred among patients who have received zanubrutinib.
