Orelabrutinib with anti-CD20 monoclonal antibodies is highly effective and well-tolerated as first-line therapy for marginal zone lymphoma

Marginal zone lymphoma (MZL) is an indolent subtype of non-Hodgkin lymphoma with heterogeneous clinical features. First-line treatment typically involves anti-CD20 monoclonal antibodies with or without chemotherapy. Although Bruton’s tyrosine kinase (BTK) inhibitors have demonstrated efficacy in relapsed/refractory (R/R) MZL, their role as first-line therapy remains unclear. This single-center retrospective study included 25 treatment-naïve patients with MZL who received orelabrutinib (150 mg once daily) plus either rituximab or obinutuzumab for 6 cycles, followed by orelabrutinib maintenance for up to 6 months. The primary endpoint was overall response rate (ORR), assessed according to the 2014 Lugano criteria. Secondary endpoints included progression-free survival (PFS), overall survival (OS), and safety. The ORR was 96.0%, comprising 12 complete response (CR) and 12 partial response (PR), with 1 case of stable disease (SD). Among the 13 patients with ocular adnexal MZL (OAML), 5 achieved CR, and 8 achieved PR. In the rituximab subgroup (n = 10), 5 patients achieved CR and 5 achieved PR, whereas in the obinutuzumab subgroup (n = 15), 7 achieved CR, 7 achieved PR, and 1 had SD; there was no significant difference in CR rate between the 2 groups (50.0% vs 46.7%, p = 1.000). Treatment-related adverse events (AEs) occurred in 32.0% of patients, with neutropenia (20.0%) and thrombocytopenia (12.0%) being the most common. Grade 3 to 4 events occurred in 12.0% of patients, with no significant differences in safety profiles between the rituximab and obinutuzumab subgroups. In conclusion, CD20 monoclonal antibodies combined with orelabrutinib may represent a feasible, low-toxicity first-line option for MZL, with favorable short-term efficacy and tolerability observed in this cohort. These preliminary findings warrant confirmation in larger prospective randomized studies to establish long-term benefits and safety.