A Retrospective Analysis of the Efficacy and Safety of Orelabrutinib-Containing Regimens in Marginal Zone Lymphoma
Authors: Zhang Hongyong , Cheng Zhipeng , Mei Heng , Sun Chunyan , Wu Yingying , Liao Danying , Zhao Fei , Hu Yu , Xia Linghui , Fang Jun 
Published: December 2024

Background and Objective: Marginal zone lymphoma (MZL) is a prevalent indolent B-cell non-Hodgkin lymphoma (NHL) that remains incurable with standard therapy. The associated treatment toxicity further constrains therapeutic options. Orelabrutinib, a novel BTK inhibitor, is known to inhibit the BCR signaling pathway, thereby reducing the abnormal activation and proliferation of B cells. It also mitigates adverse reactions caused by off-target effects, enhancing patient tolerability. Orelabrutinib is the first and the only approved BTK inhibitor for previously treated MZL patients in China. However, clinical data on the combined regimens with orelabrutinib in MZL treatment are scarce. This retrospective study aimed to evaluate the efficacy and safety of orelabrutinib-containing regimens in the treatment of MZL.

Methods: We retrospectively analyzed clinical data from MZL patients and treated with orelabrutinib-containing regimens in our center from June 2023 to July 2024. Treatment efficacy was assessed by PET-CT/CT. The main indicators observed in the study were the overall response rate (ORR), complete response (CR), progression-free survival (PFS), overall survival (OS), and the incidence of grade 3 or higher adverse events.

Results: As of July 2024, 12 MZL patients were enrolled with 5 males and 7 females. The median age was 60 years old（range 36-79）. MALT patients account for 58.3% (7/12), with 1 primary gastric MALT and 6 non-primary gastric MALT. Nodal MZL accounted for 41.7% (5/12). The Ann Arbor staging showed 58.3% (7/12) in stages III-IV, with 3 cases of bone marrow infiltration. 50% (6/12) of the patients had an International Prognostic Index score of 1-2, while 25% (3/12) had a score of 3 or higher. International According to MALT-IPI, 28.6% of patients (2/7) are low risk, 57.1% (4/7) are low-intermediate risk, and 14.2% (1/7) are high-intermediate risk. Immunohistochemical staining indicated an average Ki67(+) rate of 10% (range 5%-20%) for MALT and 25% (range 10%-40%) for NMZL. The treatment regimens included orelabrutinib combined with anti-CD20 monoclonal antibody therapy (75%, 9/12), with R-CHOP combination in 16.7% (2/12), and BR in 8.3% (1/12). Considering the advanced age and reluctance to receive chemotherapy and radiotherapy of the patients, combination therapy including orelabrutinib was used for first-line treatment in 33.3% (4 /12) and for second-line or later in 66.7% (8 /12).

The overall ORR for all patients was 100%, with a CR rate of 50%（6/12）. The median follow-up time for the 7 MALT patients was 4 months (range 3-12 months). Among these, 3 patients completed 6 or more cycles of treatment, and 4 patients used 2-5 cycles. The best CR rate was 42.8% (3/7), all achieved with orelabrutinib combined with anti-CD20 monoclonal antibodies; PR rate was 57.2% (4/7), maintaining an ORR of 100%. For the 5 NMZL patients, the median follow-up time was 3 months (range 2-4 months), with all patients using 2-5 cycles. The best CR rate was 60% (3/5), with 2 patients using orelabrutinib in combination with anti-CD20 monoclonal antibodies and 1 patient using with BR; the PR rate was 40% (2/5), and the ORR was 100%. No disease progression, recurrence, or death was observed, precluding the assessment of OS and PFS. No bleeding, atrial fibrillation, or renal function adverse events were reported. No grade 3 or more severe adverse events were noted.

Conclusion: Despite the limited patient sample, the findings suggest that orelabrutinib-containing regimens demonstrate promising safety and efficacy in MZL. Notably, the combination of orelabrutinib with anti-CD20 monoclonal antibodies emerges as a effective and safe therapeutic option for MALT MZL,which deserves further investigation.