Phase 1/2 study of single-agent zanubrutinib in patients with relapsed/refractory marginal zone lymphoma.

Background: Marginal zone lymphoma (MZL) is the third most common lymphoma and represents approximately 5% to 15% of all non-Hodgkin lymphomas. Improved understanding of the disease biology, including genetic and molecular characteristics, has changed the therapeutic landscape of MZL, and there is increasing evidence that targeted therapies, including Bruton tyrosine kinase inhibitors, have improved efficacy and have shown tolerable toxicity profiles over chemotherapy- based approaches. Zanubrutinib, a potent and selective Bruton tyrosine kinase inhibitor, has established therapeutic activity in B-cell malignancies including chronic lymphocytic leukemia, mantle cell lymphoma, and Waldenstrom macroglobulinemia. Aim(s): To examine the safety and preliminary efficacy of single-agent zanubrutinib in a phase 1/2 study of patients with relapsed/refractory MZL. Method(s): Treatment consisted of oral zanubrutinib at 160 mg twice daily (n = 17) or 320 mg once daily (n = 3) until disease progression or unacceptable toxicity. Efficacy end points included the proportion of patients achieving a complete or partial response in accordance with Lugano classification (J Clin Oncol. 2014;32:3059). Result(s): Between September 2014 and August 2018, 20 patients with relapsed/refractory MZL started treatment with zanubrutinib; 65% of patients were aged > 65, and 15% were aged > 75 years. Patient distribution across MZL subtypes was as follows: extranodal (mucosa-associated lymphoid tissue), 45%; splenic, 30%; and nodal, 25%. The median number of prior therapies was 2, with RCVP (rituximab, cyclophosphamide, vincristine, and prednisone) being the most common type of therapy. At a median follow-up of 22.16 months, 60% of patients remained on treatment. Reasons for treatment discontinuation included disease progression (25%), adverse events (AEs) in 5% of patients (with 1 patient having treatment-related diarrhea), patient's withdrawal of consent (5%), and other (5%). Therapy was well-tole