Abstract
Objective: Mucosa-associated lymphoid tissue (MALT) lymphoma represents a distinct subtype among marginal zone lymphomas (MZL). The stomach is the most frequently involved site in MALT lymphoma, but the disease can occur in mucosa-associated lymphoid tissue of all organs, including the orbit, lung, and salivary glands. Current clinical studies indicate BTK inhibitors exhibit promising efficacy in MZL. As a novel BTK inhibitor, Orelabrutinib reduces adverse reactions associated with off-target effects and improves patient tolerance. Nevertheless, clinical data on Orelabrutinib combined with Anti-CD20 monoclonal antibody for treating MALT lymphoma remains insufficient. Therefore, this study aims to evaluate the effectiveness and safety of the Orelabrutinib combined with Anti-CD20 monoclonal antibody regimen in treating MALT lymphoma through a single-center retrospective analysis.
Methods: Clinical data of MALT lymphoma patients diagnosed and treated with the Orelabrutinib combined with Anti-CD20 monoclonal antibody regimen at Union Hospital, Tongji Medical College, Huazhong University of Science and Technology between June 2023 and April 2025 were retrospectively analyzed. Treatment efficacy was assessed based on PET-CT/CT imaging or gastrointestinal endoscopy results before and after medication. Primary endpoints included: objective response rate (ORR), complete response rate (CR), progression-free survival (PFS), overall survival (OS), and incidence of adverse events.
Results: Baseline Characteristics By April 2025, this study enrolled 12 evaluable MALT lymphoma patients, comprising 4 males and 8 females. The median age was 61 years (range 30-73). Among them, 25% (3/12) had Ann Arbor stage III-IV disease, with 1 case presenting bone marrow involvement. Primary sites included gastric (n=4) and non-gastric (n=8), with non-gastric subtypes comprising pulmonary MALT lymphoma (n=4), orbital MALT lymphoma (n=2), parotid MALT lymphoma (n=1), and colonic MALT lymphoma (n=1). According to MALT-IPI stratification, 8 cases (66.7%) were low-risk and 4 cases (33.3%) were intermediate-low risk. Ten treatment-naïve MALT lymphoma patients received the Orelabrutinib combined with Anti-CD20 monoclonal antibody regimen as first-line treatment. One treatment-naïve patient received it as second-line therapy due to prior chemotherapy intolerance, while one refractory patient received this regimen as second-line treatment.
Efficacy and safety The ORR for the entire cohort was 100%, with a CR rate of 75% (9/12). The gastric MALT lymphoma subgroup comprised 4 patients with a median follow-up of 11 months. All patients received first-line treatment, achieving a CR rate of 75% (3/4). The non-gastric MALT lymphoma subgroup included 8 patients with a median follow-up of 13 months, attaining a CR rate of 87.5% (7/8). All four pulmonary MALT lymphoma patients achieved a 100% CR rate. Among them: one patient was assessed as PR after 4 cycles of R-miniCDOP regimen but switched to Orelabrutinib combined with Anti-CD20 monoclonal antibody regimen due to chemotherapy intolerance, subsequently achieving CR after 4 cycles; another patient showed progressive disease after 2 cycles of R-CDOP regimen but attained CR after switching to 4 cycles of Orelabrutinib combined with Anti-CD20 monoclonal antibody regimen. Both orbital MALT lymphoma patients achieved 100% CR. The single colonic MALT lymphoma patient reached 100% CR. One parotid MALT lymphoma patient was preliminarily assessed as PR after 2 treatment cycles. No disease progression, relapse, or death occurred among all patients; therefore, OS and PFS were not evaluated. Hematological adverse events were observed in 25% (3/12) of cases, including two grade 1 leukopenia events and one grade 2 thrombocytopenia event. No non-hematological adverse events were reported.
Conclusion: Despite the limited sample size in this retrospective study, the results indicate that the Orelabrutinib combined with Anti-CD20 monoclonal antibody regimen demonstrates favorable safety and efficacy in MALT lymphoma patients, providing an effective and safe treatment option for this population.
