Zanubrutinib plus rituximab as front-line treatment for mucosa-associated lymphoid tissue (MALT) lymphoma: A single-arm, phase II study (ZAMA).

Abstract

7080 Background: Mucosa-associated lymphoid tissue (MALT) lymphoma is the most common subtype of marginal zone lymphoma and follows an indolent clinical course. For patients with advanced-stage disease with an indication for treatment, rituximab-based immunochemotherapy is recommended as frontline therapy; however, toxicity and tolerability remain concerns. Zanubrutinib, a next-generation Bruton tyrosine kinase inhibitor, has shown promising antitumor activity with a manageable safety profile in marginal zone lymphoma. This study aimed to evaluate zanubrutinib plus rituximab as frontline treatment for MALT lymphoma. Methods: The ZAMA study (NCT06647732), a multicenter, single-arm, phase II trial, enrolled patients aged ≥18 years with histologically confirmed CD20-positive MALT lymphoma. Eligible patients had newly diagnosed advanced-stage disease or relapsed disease after prior local therapy, had not received prior systemic treatment, and had at least one measurable lesion. Patients received rituximab (375 mg/m 2 ) plus zanubrutinib (160 mg twice daily) in 28-day cycles. Treatment was administered for six cycles, after which patients achieving complete response (CR) entered observation, while those with partial response or stable disease received two additional cycles. The primary endpoint was the CR rate as best response. Results: From October 30, 2024 to December 12, 2025, 39 patients were enrolled. At the data cutoff of January 10, 2026, 23 patients had completed protocol-specified treatment, including 14 patients who received six cycles and 9 patients who received eight cycles. The median age was 58 years (range 24–75); 7 patients were males (30.4%). Most patients (n = 21, 91.3%) had an ECOG performance status of 0–1, and 21 patients (91.3%) had Ann Arbor stage III–IV disease; two patients had relapsed disease after prior local therapy. Eighteen patients (78.2%) achieved CR, and the remaining five patients achieved PR. Treatment-emergent adverse events (TEAEs) occurred in 20 patients (87.0%); hematologic toxicity were most common: neutropenia (n = 2, 8.7%), and thrombocytopenia (n = 2, 8.7%). Grade ≥ 3 TEAEs occurred in 4 patients (17.4%), most frequently neutropenia (n = 2, 8.7%), and thrombocytopenia (n = 2, 8.7%). Conclusions: Preliminary results from the ZAMA study show that frontline zanubrutinib plus rituximab provides encouraging efficacy with manageable safety in MALT lymphoma. The study is ongoing, and patient enrollment is continuing. Clinical trial information: NCT06647732 . Baseline characteristics. Characteristics Patients (n=23) Age, years (median [range]) 58 (24-75) Sex MaleFemale 7 (30.4%)16 (69.6%) ECOG PS 0-12 21 (91.3%)2 (8.7%) Ann Arbor stage III-IV 21 (91.3%) Prior local therapy 2 (8.7%) MALT-IPI score 0 1 (4.3%) 1 21 (91.3%) 2 1 (4.3%) Bone marrow involvement 4 (17.4%)