Orelabrutinib-Bruton Tyrosine Kinase Inhibitor-Based Regimens in the Treatment of Marginal Zone Lymphoma: A Retrospective Study
Authors: LI He , Liu Jiazhuo , Chen Yuhui , Tuohuti Pazilaiti , Wang Yutong , Tang Xinzhu , Xiang Bing , Jia Yongqian , Wu Yu , Tang Yun , Guo Yong , Wang Jie , Zheng Yuhuan , Liu Yu , Niu Ting 
Published: December 2024

Background:
Marginal zone lymphoma (MZL) is a subtype of indolent non-Hodgkin lymphomas. The optimal frontline management of MZL is not well defined. Approximately 20% of patients with marginal zone lymphoma (MZL) relapse or experience disease progression within 2 years after first-line treatment. These patients with relapsed/refractory (r/r) MZL have poor clinical. In recent years, advances in the understanding of MZL have revealed the importance of the B-cell receptor signaling pathway and the involvement of Bruton tyrosine kinase (BTK) in the B-cell receptor's downstream transduction pathway. Orelabrutinib is a novel, oral, and covalent next-generation BTK inhibitor with high target selectivity. Orelabrutinib has shown favorable efficacy and safety in MZL and has been approved in China for the treatment of MZL in patients who have received at least one prior treatment. Thus, we conducted a retrospective study to evaluate the efficacy and safety of orelabrutinib-based regimens for MZL.
Methods:
This is a retrospective study involving all patients with marginal zone lymphoma who had been evaluated for response to orelabrutinib at the Department of Haematology, West China Hospital of Sichuan University, China. We analyzed the characteristics and real-world clinical outcomes of patients with MZL.
Results:
As of Jul. 19, 2024, 25 patients(pts) were enrolled. Of 25 pts, the median age was 59.0 (range, 24.0-81.0) years. MZL subtypes included extranodal (mucosa associated lymphoid tissue) in 72%, nodal in 20% and splenic in 8% of pts. Other baseline characteristics included 80% stage II-IV disease, 32% Ki67 index (≥20%), 80% intermediate and high-risk MZL-IPI scores and 20% B symptoms. Orelabrutinib was administered as a first-line treatment for 14 pts and as a second-line or later-line treatment for 11 patients. Among the 14 untreated pts with a median age of 58.5 years, the treatment regimens were as follows: orelabrutinib alone for 2 pts, orelabrutinib combined with anti-CD20 monoclonal antibody for 10 pts, orelabrutinib combined with anti-CD20 monoclonal antibody and lenalidomide for 1 pt, and orelabrutinib combined with chlorambucil for 1 pt. With a median follow-up time of 9 (range 4.3 - 27.1) months, the overall response rate (ORR) was 85.7%, with 5 pts achieving a complete response (CR). The 24-month progression-free survival (PFS) rate was 80%. Regarding the 11 pts who received later-line therapy, the median age was 67 years, with treatment regimens including orelabrutinib monotherapy for 8 pts, orelabrutinib plus an anti-CD20 monoclonal antibody for 2 pts, and orelabrutinib plus BR (bendamustine and rituximab) for 1 pt. The median follow-up time in this group was 4.5 months (range 2.9-20.9 months), with an ORR of 91% and 4 pts achieving CR. The 12-month PFS rate was 87.5%. Among 25 pts in the study, 12 (48.0%) experienced adverse events, and 4 pts had grade 3 or higher adverse events. The most common grade 3 or higher adverse events was neutropenia (12.0%). At the time of data cut-off, no deaths were observed.
Conclusions:
This retrospective data indicates promising anti-tumor activity of chemotherapy-free regimens based on orelabrutinib in MZL. Prospective studies are warranted to guide orelabrutinib in MZL.