Orelabrutinib, a next-generation BTK inhibitor, demonstrated sustained efficacy against relapsed/refractory marginal zone lymphoma (MZL), regardless of disease subtype, in a phase 2 trial. The safety profile was manageable and orelabrutinib was considered well tolerated, according to the data presented at the International Conference on Malignant Lymphoma 2023.

The open-label, phase 2 trial treated 90 patients with centrally-confirmed relapsed/refractory MZL with orelabrutinib (ClinicalTrials.gov identifier: NCT03797456). The primary endpoint was objective response rate (ORR) and the secondary endpoints included progression-free survival (PFS), duration of response (DOR), and overall survival.

The median age at baseline was 62 years and 54.4% of patients were male. The most common MZL subtype in the cohort was mucosal at 42%, followed by nodal at 32% and other at 16%. The median number of prior lines of therapy was 2 (range, 1-3), with 92.2% of patients previously treated with an anti-CD20 agent. Prior BTK inhibitor treatment was not allowed. There were 35.6% of patients who were refractory to their last treatment.

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The ORR was 58.9%, which included 11% of patients who achieved a complete response. When stratified by MZL subtype, the ORR was 75% for patients with nodal disease, 48% with mucosal, and 56% for other subtypes. The median DOR was 34.3 months, the median PFS was not yet reached, and the 2-year rate as 75.8%.

The most common treatment-related adverse events (TRAEs) of any grade were hematologic and blood present in the urine. The most common grade 3 or higher TRAEs were neutrophil count decrease and pneumonia. There were no cases of atrial fibrillation or flutter.

“The results of this study support orelabrutinib as an effective treatment option for relapsed/refractory MZL patients,” the authors concluded in their presentation.

Disclosures: This research was supported by Beijin InnoCare Pharma Tech Co., Ltd.


Song Y, LI Z, Zhang H, et al. Orelabrutinib for the treatment of relapsed or refractory marginal zone lymphoma: a phase 2, multicenter, open-label study. ICML 2023. June 13-17, 2023. Abstract 283.