According to the results of a subgroup analysis reported in Blood Advances, the highly selective Bruton’s tyrosine kinase inhibitor zanubrutinib yielded a high response rate and extended progression-free survival (PFS) in patients with relapsed/refractory (R/R) mantle cell lymphoma (MCL).

The participants were from a recently completed phase 1/2 first-in-human, multicenter, open-label study evaluating zanubrutinib in adult patients with B-cell malignancies ( Identifier: NCT02343120).

The report detailed the results for 32 patients with R/R MCL receiving a total daily dose of 320 mg of zanubrutinib, given orally once (320 mg; n=18) or twice (160 mg; n=14) daily in 28-day cycles until progressive disease (PD) or unacceptable toxicity. The primary efficacy endpoint was overall response rate (ORR), including partial response (PR) or complete response (CR), as assessed by an independent review committee (IRC; per the Lugano classification). Safety assessments included treatment-emergent adverse events (TEAEs) and predefined AEs of interest.

Continue Reading

The median study follow-up was 18.8 months. The ORR was 84% (27 of 32 patients), with 25% of patients achieving a CR (n=8). Stable disease and PD was reported for 2 patients (6.3%) each. The median time to response (CR+PR) and to CR were 2.8 months (range, 1.9-9.8) and 5.5 months (range, 1.9-11.1), respectively. Responses were not significantly different between the 160 mg twice daily or the 320 mg once daily dosing regimens and were independent of baseline characteristics. The median duration of response was 18.5 months, and the median PFS was 21.1 months.

Zanubrutinib was considered well tolerated. In total, 18 patients discontinued treatment (10 from PD and 8 from AEs; 1 AE was considered related to zanubrutinib treatment [peripheral edema]). AEs led to dose interruptions in 16 patients and dose reduction in 1 patient.

The most common TEAEs of any grade were diarrhea (43.8%), contusion (37.5%), constipation (31.3%), and upper respiratory tract infection (31.3%). The most common AEs of interest of any grade were infection (68.8%), bleeding (56.3%), second primary malignancies (18.8%), and anemia, neutropenia, and thrombocytopenia (12.5% each). Grade ≥3 AEs were reported in 59.4% of patients; these included anemia (12.5%), pneumonia (9.4%), and myalgia (9.4%).

The limitations of the study included the small sample size and single-arm design.

“[The results] add to a now large and growing body of zanubrutinib data, demonstrating its benefits, including potent durable responses and an encouraging safety profile in patients with MCL who have received ≥1 prior therapy,” the authors wrote. “Viewed in

the context of the poor outcomes associated with R/R MCL and currently available treatment options, the benefit-risk profile for zanubrutinib is favorable, suggesting that it offers a promising treatment option for patients with R/R MCL.”

Disclosure: This research was supported by BeiGene (Beijing) Co., Ltd. Please see the original reference for a full list of authors’ disclosures. 


Tam CS, Opat S, Simpson D, et al. Zanubrutinib for the treatment of relapsed or refractory mantle cell lymphoma. Blood Adv. 2021;5(12):2577-2585. doi:10.1182/bloodadvances.2020004074