Orelabrutinib, a new‐generation bruton tyrosine kinase inhibitor, demonstrates safety and efficacy in relapsed/refractory marginal zone lymphoma

Abstract

Introduction: Marginal zone lymphoma (MZL) is an indolent type of non-Hodgkin lymphoma that develops through pathological B cell receptor signaling. Orelabrutinib, a new-generation oral small molecule Bruton’s tyrosine kinase (BTK) inhibitor, was evaluated in relapsed/refractory (r/r) MZL patients. Methods: Previously treated r/r MZL patients received orelabrutinib 150 mg once daily in a phase 2, multicenter, single-arm study conducted in China. The primary endpoint was overall response rate (ORR) assessed by an Independent Review Committee (IRC) based on the Lugano 2014 classification. Other efficacy, safety, and pharmacokinetic parameters were evaluated as secondary outcome measures. Results: Between April 2019 and November 2021, 111 Chinese patients with a median age of 60 y/o (range 23–77) were enrolled. Among those, 83 patients who received at least 1 prior therapy with an anti-CD20 antibody-containing regimen were confirmed with MZL by the central pathological review, who were mainly with extranodal MZL of mucosa-associated lymphoid tissue (MALT, 45.8%) and nodal MZL (36.1%). The majority had late-stage diseases, the stage IV accounting for 75.9%. After a median follow-up of 22.3 months, the IRC-assessed ORR was 57.8% (95% CI, 46.5% to 68.6%). Ten patients achieved a complete response (CR, 12%), and 38 achieved a partial response (PR, 45.8%). The IRC-assessed median duration of response (DoR) and median progression-free survival (PFS) was 34.3 months and 36.0 months, respectively, with a 12-month PFS rate of 84.3% (95% CI, 73.9% to 90.8%). The rate of overall survival (OS) was 91.5% (95% CI, 82.9% to 95.8%) at 12 months. Treatment was well tolerated with most treatment-related adverse events (TRAE) being grade 1 or 2. In all the 111 patients, common all-grade TRAEs included anemia (27.9%), neutrophil count decrease (23.4%), white blood cell count decrease (18.0%), platelet count decrease (17.1%), rash (14.4%), and upper respiratory tract infection (10.8%). Thirty-four patients (30.6%) experienced grade 3 or higher TRAEs. Serious TRAEs occurred in 18 patients (16.2%), of which pneumonia (5.4%) was the most common. Seven patients (6.3%) discontinued orelabrutinib due to TRAEs. Conclusions: Orelabrutinib demonstrated high response rates with durable disease remission and was well tolerated in Chinese patients with r/r MZL. This trial is registered at ClinicalTrials.gov as NCT03797456. Keyword: Indolent non-Hodgkin lymphoma No conflicts of interests pertinent to the abstract.