The efficacy and safety of orelabrutinib-based regimens in the treatment of marginal zone lymphoma: A retrospective real-world study

Abstract

Abstract Background: Bruton's tyrosine kinase (BTK), a pivotal regulator of B-cell receptor (BCR) signaling, plays a critical role in the survival, proliferation, and migration of malignant B cells. Orelabrutinib, a novel, highly selective and irreversible BTK inhibitors, has emerged as a promising candidate for the treatment of B-cell lymphoma. This study was conducted to evaluate the preliminary efficacy and safety of Orelabrutinib-based regimens for marginal zone lymphoma (MZL) patients. Methods: This was a retrospective real-world study in patients with clinical and histopathological confirmed MZL in China. We retrospectively investigated the clinical information and treatment outcome of 38 MZL patients between 2022 and 2025. Results: 38 MZL patients were enrolled in the study. Among them, 17 patients (44.7%) received orelabrutinib-based regimens, with the median treatment duration of 4 months (range, 1 - 13 months). The median age was 66 years (range, 52 - 81 years), with 9 males (52.9%). There were 12 cases (70.6%) of extranodal MZL (involving the breast, stomach, kidney, bone marrow, chest wall, etc.), 3 cases (17.6%) of nodal MZL, and 2 cases (11.8%) of splenic MZL. Moreover, 10 patients (58.8%) had an ECOG score of 0–1, 6 patients (35.3%) had B symptoms, 11 cases (64.7%) were Ann Arbor stage III–IV, 15 cases (88.2%) had an MZL International Prognostic Index (MZL-IPI) score of 1–2, and 6 cases (35.3%) had bone marrow involvement. In the total of 38 MZL patients, 22 cases had evaluable response evaluation. MZL patients in the orelabrutinib-based regimens group (n=9) did not have a superior overall response rate (ORR) compared with control group [77.8% (7/9) vs. 76.9% (10/13)]. Interestingly, MZL patients received orelabrutinib-based regimens achieved a significantly higher complete response rate (CRR) [66.7% (6/9) vs. 15.4% (2/13)]. Notably, all 7 patients who received orelabrutinib maintenance therapy achieved an ORR of 100%, whereas the 2 patients without orelabrutinib maintenance therapy had an ORR of 0%. In the orelabrutinib–based regimens group (n=17), none of the remaining 8 MZL patients experienced disease progression, yielding an overall disease control rate (DCR) of 94.1% (16/17). With a median follow-up of 343 days (range, 36–1166 days), neither median overall survival (OS) nor progression-free survival (PFS) was reached. Moreover, no grade ≥3 adverse events were observed in the study. Conclusions: Our preliminary results suggested that orelabrutinib-based regimens may be a well-tolerated and effective regimen in MZL patients. Future studies with a large sample size and longer follow-up time are needed to validate the conclusion.