In August 2023, a study led by Professor Jun Zhu from Peking University Cancer Hospital and Institute was published in the prestigious international academic journal ——Blood Advances (IF=7.642). The title of the study is "Orelabrutinib for the treatment of relapsed or refractory MCL: a phase 1/2, open-label, multicenter, single-arm study". This study findings indicate that Orelabrutinib exhibits significant efficacy and good tolerability in patients with relapsed/refractory (r/r) mantle cell lymphoma (MCL).
Mantle cell lymphoma (MCL) represents a distinct subtype of B-cell non-Hodgkin lymphoma, characterized by its aggressive nature and poor prognosis, particularly in the relapsed or refractory (r/r) setting. The advent of Bruton’s tyrosine kinase (BTK) inhibitors marked a significant advancement in the treatment landscape of MCL, with ibrutinib being the pioneering agent in this class. Despite its effectiveness, ibrutinib is associated with several toxicities that can lead to treatment discontinuation. In this context, orelabrutinib emerges as a novel, next-generation BTK inhibitor with enhanced selectivity and an improved safety profile, aiming to address the limitations of existing therapies.
This multicenter, open-label phase 1/2 study was meticulously designed to evaluate the therapeutic potential of orelabrutinib in patients with r/r MCL. We enrolled patients across various centers who were then administered oral orelabrutinib at dosages of either 150 mg once daily or 100 mg twice daily. Treatment continued until either disease progression was observed or unacceptable toxicity levels were reached. The investigation primarily focused on determining the overall response rate (ORR) to orelabrutinib treatment. Secondary endpoints included evaluating the duration of response (DOR), progression-free survival (PFS), and overall survival (OS), which provided a comprehensive understanding of the drug’s efficacy.
The study’s findings, after a median follow-up period of 23.8 months, underscored the significant efficacy of orelabrutinib in treating r/r MCL. The ORR stood at an impressive 81.1%, with complete responses observed in 27.4% of the patients and partial responses in 53.8%. The analysis of secondary endpoints revealed a median DOR of 22.9 months and a median PFS of 22.0 months, indicating the durability of orelabrutinib’s therapeutic effect. Moreover, the median OS had not been reached by the study’s end, with a 24-month OS rate of 74.3%, underscoring the potential life-extending benefits of the treatment. Notably, orelabrutinib was generally well-tolerated among patients, with the majority of adverse events classified as Grade 1 or 2 in severity. The most commonly reported adverse events included thrombocytopenia, upper respiratory tract infections, and neutropenia, indicating a manageable safety profile.
(Blood Adv. 2023 Aug 22;7(16):4349-4357. )
The study’s outcomes firmly establish orelabrutinib as a potent therapeutic option for patients with r/r MCL, demonstrating both high efficacy and an acceptable safety profile. The high ORR and durable responses highlight orelabrutinib’s potential to fill the therapeutic gap left by existing treatments. Furthermore, the manageable toxicity profile of orelabrutinib represents a significant improvement over older BTK inhibitors, potentially leading to better treatment adherence and outcomes for patients. These findings are particularly promising in the context of MCL’s aggressive nature and the limited options available for relapsed or refractory cases.
The phase 1/2 study of orelabrutinib in patients with r/r MCL has provided compelling evidence of its efficacy and safety, marking it as a promising addition to the MCL treatment paradigm. The results suggest that orelabrutinib could offer patients a highly effective treatment option with a manageable side effect profile, addressing a crucial need in the MCL patient community. Future studies are necessary to further validate these findings and to directly compare orelabrutinib’s performance against other BTK inhibitors in head-to-head trials, which could definitively position orelabrutinib within the broader oncological treatment landscape.
