Zanubrutinib for the treatment of relapsed or refractory mantle cell lymphoma

• Published in: Blood advances 2021-06, Vol.5 (12), p.2577-2585
• Main Authors: Tam, Constantine S., Opat, Stephen, Simpson, David, Cull, Gavin, Munoz, Javier, Phillips, Tycel J., Kim, Won Seog, Rule, Simon, Atwal, Siminder Kaur, Wei, Rachel, Novotny, William, Huang, Jane, Wang, Michael, Trotman, Judith
• Format: Article
• Language: English
• Subjects: Clinical Trials and Observations
• ISSN: 2473-9529; 2473-9537
• DOI: 10.1182/bloodadvances.2020004074

•Zanubrutinib provided a high response rate (84%) and extended PFS (median 21 months) in patients with R/R MCL.•Tolerability was favorable, with few adverse events requiring treatment discontinuation or dose reduction. [Display omitted] Zanubrutinib, a highly selective Bruton tyrosine kinase inhibitor, was evaluated in a phase 1/2 study in patients with various B-cell malignancies. In the subgroup of patients with relapsed/refractory (R/R) mantle cell lymphoma (MCL), zanubrutinib was administered as 160 mg twice daily (n = 14), 320 mg once daily (n = 18), or ≤160 mg total dose (n = 5). Herein, we report results for patients receiving a total daily dose of 320 mg (N = 32). Median study follow-up was 18.8 months. Eighteen patients discontinued treatment, 10 because of progressive disease and 8 because of adverse events (AEs); 1 AE (peripheral edema) was considered to be related to zanubrutinib treatment. The most common AEs were diarrhea (43.8%), contusion (37.5%), constipation (31.3%), and upper respiratory tract infection (31.3%). Infection was the most commonly reported AE of interest (18.8% of patients experienced grade ≥3 infection). At least 1 AE of grade ≥3 was reported in 59.4% of patients; grade ≥3 AEs that were reported in >2 patients were anemia (12.5%), pneumonia (9.4%), and myalgia (9.4%). Overall response rate was 84%, with 25% achieving a complete response. Median duration of response was 18.5 months. Median progression-free survival (PFS) was 21.1 months. Zanubrutinib was well tolerated and demonstrated activity in patients with R/R MCL. The trial is registered at www.clinicaltrials.gov as #NCT02343120.