A Retrospective Analysis of Orelabrutinib-Containing Regimen for Marginal Zone Lymphoma

Background: Marginal zone lymphoma (MZL) is the second most prevalent B-cell lymphoma in China, with a proportion of 12.4%. To date, there is no established standard systemic treatment for MZL. Traditional immunochemotherapy regimens such as BR and R-CHOP are commonly used, but they are associated with a high incidence (60-70%) of grade 3 or higher adverse events, which severely limits patient benefit. There is an urgent need for safer and effective treatment strategy. Orelabrutinib, a novel Bruton's tyrosine kinase inhibitor, offers higher kinase selectivity and a favorable safety profile. A phase II study of orelabrutinib monotherapy for relapsed/refractory MZL showed an objective response rate (ORR) of 58.9%, with a median duration of response of 34.3 months, and orelabrutinb has been approved in China for the treatment of previously treated MZL. This study retrospectively analyzed the efficacy and safety of treatment orelabrutinib-containing regimens for MZL.

Methods: This retrospective study included 15 MZL patients treated with orelabrutinib-containing regimens at our center between April 2023 and June 2024. Each treatment cycle was 28 days. The regimens included orelabrutinib monotherapy (O), orelabrutinib combined with rituximab (OR), orelabrutinib combined with rituximab and lenalidomide (OR2), and orelabrutinib combined with rituximab and pomalidomide (POR), every 28 day for a cycle. The specific dosages were: orelabrutinib 150 mg, once daily; rituximab 375 mg/m², d1; lenalidomide 20 mg, d1-d21; pomalidomide 4 mg, d1-d21. The primary endpoint was objective response rate (ORR), and secondary endpoints included complete response rate (CR), progression-free survival (PFS), overall survival (OS), and safety.

Results: Fifteen patients (6 males, median age 60, range 33-69) were included in the study, comprising 14(93.3%) cases of extranodal MZL and 1(6.7%) case of nodal MZL. Nine(60.0%) patients were in stages III-IV, 3(20%) patients had an MZL-IPI score ≥3, 3(20%) had Hepatitis B virus, 1(6.7%) had Epstein Barr virus, and 1(6.7%) had Helicobacter pylori(Hp). One(6.7%) patient had received local treatment (anti-Hp therapy), and 6(40%) had received systemic treatment. For the current regimens, 2(13.3%) patients received orelabrutinib monotherapy, 4(26.7%) received OR treatment, 7(46.7%) received OR2 treatment, and 2(13.3%) received POR treatment. Among the 10 evaluable patients, the ORR was 80.0% (5 CR, 3 PR), with 2 (20.0%) cases of disease progression. Three (20.0%) patients experienced adverse events: 1 had neutropenia (Grade 3) and lymphopenia (Grade 2), 1 had a rash (Grade 2), and 1 had a hemoptysis (Grade 2). No BTKi-related adverse events were observed.

Conclusion:This retrospective study preliminarily confirmed that orelabrutinib-containing regimens are effective and safe for treating MZL. Further long-term follow-up and additional studies are anticipated to validate these findings.

No relevant conflicts of interest to declare.