Researchers Report Further Analysis of Zanubrutinib Monotherapy for R/R MCL

In a recent report, researchers reported pooled data from 2 studies to explore the efficacy of zanubrutinib monotherapy in relapsed/refractory (R/R) mantle cell lymphoma (MCL).

MCL almost always relapses, and before the advent of Bruton tyrosine kinase (BTK) inhibitors, therapeutic options were limited. Zanubrutinib is a next-generation, targeted, and potent BTK inhibitor approved by the FDA in 2019. Besides being approved for MCL, it is also approved for Waldenström macroglobulinemia.

A total of 112 patients were included in the 2 studies, 33 from BGB-3111-AU-003 and 79 from BGB-3111-206; these 2 studies were used in its 2019 US approval. Researchers used patient-level data from the phase 1 and 2 trials to add additional knowledge about zanubrutinib’s efficacy.

Median follow-up durations were 24.7 and 24.9 months for BGB-3111-AU-003 and BGB-3111-206, respectively.

Overall, across the 2 trials, 77% of the patients were male with a mean age of 61.5. Most had advanced disease (stage III or stage IV). A little more than half had bone marrow involvement, while 8% had bulky disease and 13% had blastoid variant.

Most also had low-to-intermediate MCL International Prognostic Index (MIPI) risk scores (79%).

Before weighting, there were 41 patients in the second-line group and 71 patients in the later-line group. Compared with the later-line group, patients in the second-line group had higher age, body mass index (BMI) and a higher percentage with high MIPI risk scores and lower percentages with extra nodal disease and blastoid subtype.

After weighting, covariates were balanced between the 2 groups.

The effective sample sizes were 27 in the second-line group and 59 in the later-line group, with median treatment durations of 22 and 18.8 months, respectively.

After weighting, the progression-free survival (PFS; median, not estimable [NE] vs. 21.1 months, P = .235) and overall survival (OS; median, NE vs. 38.2 months, P = .057) were similar but numerically better in the second-line than later-line group.

In second- and later-line therapy groups, prior treatment regimens included:

  • Cyclophosphamide/vincristine/doxorubicin/dexamethasone (hyper-CVAD) or hyper-CVAD-like regimens, 9% and 19%, respectively
  • Lenalidomide, 0% and 14%
  • Bortezomib, 1% and 10%
  • Autologous stem cell transplantation, 2% and 10%

The percentage of patients who received prior bendamustine was low in both groups (4% in second-line and 5% in later-line).

Overall response rate (ORR) and complete response (CR) rate were 84.8% and 62.5%.

Median duration of response, PFS, and OS were 24.9, 25.8 and 38.2 months, respectively.

The authors said zanubrutinib was well-tolerated. Treatment discontinuation and dose reduction for adverse events (AEs) were 12.5% and 2.7% of patients, respectively.

Hypertension, major hemorrhage and atrial fibrillation/flutter rates were 11.6%, 5.4% and 1.8%, respectively.


Zhou K, Zhou D, Zhou J, et al. Zanubrutinib monotherapy in relapsed/refractory mantle cell lymphoma: a pooled analysis of two clinical trials. J Hematol Oncol. Published online October 14, 2021. doi: 10.1186/s13045-021-01174-3.