In November 2023, a study led by Professor Jun Zhu from Peking University Cancer Hospital and Institute was published in the prestigious international academic journal ——American Journal of Hematology (IF=12.8). The title of the study is "Orelabrutinib for the treatment of relapsed or refractory marginal zone lymphoma: A phase 2, multicenter, open-label study". This study findings indicate that Orelabrutinib exhibits a high response rate, durable disease remission, and good tolerability in Chinese patients with relapsed/refractory (r/r) marginal zone lymphoma (MZL).
Marginal zone lymphoma (MZL) is a subtype of non-Hodgkin lymphoma characterized by a slow progression. It originates from B cells in the marginal zone of lymphoid tissues and is associated with chronic inflammation. MZL encompasses three distinct entities: extranodal MZL of mucosa-associated lymphoid tissue (MALT lymphoma), nodal MZL, and splenic MZL. Despite being considered indolent, treatment options for relapsed or refractory (r/r) MZL are limited, and the disease can significantly impact patients’ quality of life.
Bruton’s tyrosine kinase (BTK) plays a crucial role in B cell receptor (BCR) signaling, which is pivotal for the survival and proliferation of malignant B cells. Orelabrutinib, a novel, highly selective, and irreversible BTK inhibitor, has emerged as a potential therapeutic agent for B cell malignancies, including MZL. By inhibiting BTK, orelabrutinib interferes with BCR signaling, leading to the death of malignant B cells.
This phase 2, single-arm, open-label study was conducted across multiple centers in China. It enrolled 111 patients with previously treated r/r MZL who had received at least one prior line of therapy. Participants were administered orelabrutinib 150 mg orally once daily until disease progression or unacceptable toxicity was observed.
The primary endpoint of the study was the overall response rate (ORR), determined by an Independent Review Committee (IRC) according to the Lugano 2014 classification for lymphomas. Secondary endpoints included the safety profile, pharmacokinetic profile, duration of response (DoR), progression-free survival (PFS), and overall survival (OS) rates.
The study reported an ORR of 58.9% at a median follow-up of 24.3 months, with complete response (CR) observed in 11.1% of patients and partial response (PR) in 47.8%. The median DoR was 34.3 months, indicating durable responses in a significant proportion of patients. PFS and OS rates were promising, with a 12-month PFS rate of 82.8% and a 12-month OS rate of 91.0%.
Treatment-related adverse events (TRAEs) were generally manageable and included anemia, neutrophil count decrease, and rash as the most common all-grade events. The safety profile was consistent with that observed in other BTK inhibitor studies, suggesting that orelabrutinib is well-tolerated among r/r MZL patients.
