Real-World Efficacy and Safety of Orelabrutinib in Marginal Zone Lymphoma: A Retrospective Analysis of Mucosa-Associated Lymphoid Tissue Lymphoma Patients
Authors: Zheng Miao , Li Tongjuan , Hong Zetong , Liu Min , Ma Yaxian , Yin Qing , Hong Zhaoyang , Zhao Lei , Wei Jia , Zhang Yicheng 
Published: December 2024

Background: Mucosa-associated lymphoid tissue lymphoma (MALT) constitutes a subtype of marginal zone lymphoma (MZL). Treatment with Bruton's tyrosine kinase (BTK) inhibitors has emerged as a promising therapeutic strategy in B-cell lymphoma, as evidenced by previous studies. BTK, a member of the TEC family of non-receptor kinases, plays a crucial role in B-cell development and its dysregulation is linked to B-cell malignancies. In the therapy of MALT, BTK inhibitors have been applied to a certain extent and have shown certain application prospects. Orelabrutinib is a novel and highly selective BTK inhibitor, and relevant clinical trials have been conducted in MALT therapy, but real-world studies are still scarce. This retrospective study aimed to evaluate the efficacy and safety of orelabrutinib-based chemotherapy and monotherapy in a real-world MALT patient population.

Methods: This retrospective study included patients aged 18 to 80 years old who had received at least 2 cycles of orelabrutinib combined with chemotherapy or monotherapy. The effectiveness of the treatment was assessed by PET/CT or other examination items in accordance with the Lugano 2014 evaluation criteria. The safety of the treatment was evaluated through observation and follow-up in accordance with CTCAE-Version 5.0. The primary endpoints were the overall response rate (ORR), and the secondary endpoints were the complete response rate (CR), progression-free survival (PFS), overall survival (OS), and safety.

Results: The study population comprised 19 patients with MALT lymphoma, including 9 males and 10 females. The majority, 17 patients, were newly diagnosed, with the remaining 2 presenting with recurrent-refractory disease. The median age was 54 years, with an age range of 33 to 75 years. The disease primarily affected sites such as the lungs, parotid gland, mediastinum, stomach, rectum, and orbital cavity, with two cases noted for bone marrow infiltration. According to the Lugano staging criteria from 2014, 36.84% (7/19) of patients were classified as stage III or higher. Within this group, 31.58% (6/19) scored 2 or higher on the International Prognostic Index (IPI).

At the time of analysis on July 31, 2024, the median follow-up time was 242 days, with a median treatment duration (DOT) with orelabrutinib of 138 days. Throughout the course of the study, there were no instances of disease progression or mortality among the participants, underscoring the positive outcomes associated with the treatment approach. Among the 18 patients assessed, the ORR was 94.44%（17/18）, the CR was 33.33%（6/18）. Hematological adverse events occurred in 9 patients (47.37%), of which 6 cases were grade 1. Leukopenia was the most common abnormality, and 1 case had hematological adverse events of grade 3 or above. No grade 4 adverse events. 52.63%(10/19) had non-hematological adverse events, the most common being respiratory tract infection. Among them, 4 patients (21.5%) had grade 3 adverse events (all respiratory tract infections). No patients discontinued the drug due to adverse events, and 2 patients had a temporary reduction of orelabrutinib due to adverse events (rash), and the adverse events improved after observation. Generally, most patients had mild adverse events and improved after treatment or observation.

Conclusion: The findings from this retrospective study suggest that orelabrutinib-based combined chemotherapy or maintenance therapy is highly effective in newly diagnosed MALT patients and shows promise in treating relapsed and refractory MALT in the real world. Orelabrutinib is a viable option for both initial and maintenance therapy in MALT. Furthermore, orelabrutinib treatment was found to be safe, with patients exhibiting good compliance.