Updated Efficacy and Safety Data Continue to Support Zanubrutinib Use in Released/Refractory MCL


Updated data from a pivotal trial that led to the approval of zanubrutinib for the treatment of patients with relapsed or refractory mantle cell lymphoma appears to highlight persistent benefit.

Long-term safety and efficacy data from the phase 2 BGB-3111-206 trial (NCT03206970) of single-agent zanubrutinib (Brukinsa) continues to show durable responses and a manageable safety profile in patients with relapsed/refractory mantle cell lymphoma (MCL), according to data published in Blood.1

With almost 3 years of follow-up, updated results from the study revealed an objective response rate (ORR) of 83.7% (95% CI, 74.2%-90.8%+) and a median response duration that was not reached (95% CI, 2.3-36.2+) in patients treated with the highly selective Bruton tyrosine kinase inhibitor. The pivotal clinical trial initially led to the accelerated approval of the agent in adult patients with MCL who have received at least 1 prior therapy in November 2019.2

“This phase 2 study in patients with [relapsed/refractory] MCL with extended 35.3-month follow-up data continued to demonstrate a favorable benefit–risk profile of zanubrutinib monotherapy. Approximately 50% of patients remain progression free at 36 months,” wrote the study authors who were led by Yuqin Song, MD, PhD.

The current analysis looked at results in 86 patients with MCL who received 160 mg of zanubrutinib twice daily. The primary end point of the trial was ORR and secondary end points included progression-free survival (PFS), time to response, duration of response, and safety.

Patients had a median age of 61 years (range, 34-75) and the majority were men (77.9%). Most participants had intermediate- or high-risk combined MCL International Prognostic Index (MIPI-b; 83.7%), stage III/IV disease (90.7%), and extranodal disease (70.9%). Blastoid variant disease was present in 14.0%.

Median treatment duration was 27.6 months (range, 0.2-41.6) and 45.3% of patients were still on treatment at the median follow-up. Of the patients who discontinued treatment, the most common reasons included progressive disease (43%), adverse events (AEs; 9.3%), physician’s decision (1.2%), and withdrawal of consent after achieving complete response (CR; 1.2%).

Responses were comprised of 67 CRs (77.9%) and 5 partial responses (5.8%). Eight patients (9.3%) had progression disease (PD) and 1 was reported as having stable disease (1.2%); 5 (5.8%) discontinued prior to first assessment. Median time to response was 2.7 months (range, 2.5-3.0) and median time to CR was 2.8 months (range, 2.5-16.7).

Median PFS was 33.0 months (95% CI, 19.4–not evaluable) and rates of PFS at 24 and 36 months were 58.3% (95% CI, 46.9%-68.2%) and 47.6% (95% CI, 36.2%-58.1%), respectively. The median OS was not reached, with rates at 24 and 36 months of 80.4% (95% CI, 69.9%-87.5%) and 74.8% (95% CI, 63.7%-83.0%), respectively.

No apparent response outcome variability was evident in patient subgroups, and this extended to those with poor prognosis. However, better duration of response and PFS were noted in those with low- or intermediate-risk MIPI-b scores, Ki67 index at or below 30%, few lines of therapy, and TP53 wild-type disease.

No new safety signals were noted at the updated analysis. Treatment-emergent AEs (TEAEs) occurring in 20% or more of patients, most of which were grade 1/2, were neutrophil count decreased (46.5%), upper respiratory tract infection (38.4%), rash (36.0%), white blood cell count decreased (33.7%), and platelet count decreased (32.6%). Common TEAEs of grade 3 or greater were neutrophil count decreased (18.6%), pneumonia (12.8%), platelet count decreased, white blood cell count decreased (7.0% each), and anemia (5.8%). Most AEs occurred during the earlier stages of treatment.


  1. Song Y, Zhou K, Zou DH, et al. Zanubrutinib in relapsed/refractory mantle cell lymphoma: long-term efficacy and safety results from a phase 2 study. Blood. Published March 18, 2022. doi:10.1182/blood.2021014162
  2. FDA grants accelerated approval to zanubrutinib for mantle cell lymphoma. News release. FDA. November 14, 2019. Accessed April 4, 2022. https://bit.ly/3x4T8IS

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