Addition of BTK inhibitor orelabrutinib to rituximab improved anti-tumor effects in B cell lymphoma

• Main Authors: Hui Yu, Xing Wang, Jiao Li, Yingying Ye, Dedao Wang, Wei Fang, Lan Mi, Ning Ding, Xiaogan Wang, Yuqin Song, Jun Zhu
• Format: Article
• Language: English
• Published: Elsevier 2021-06-01
• Series: Molecular Therapy: Oncolytics
• Subjects: anti-CD20 antibody; BTK inhibitor; B cell lymphoma; combined effects
• Online Access: http://www.sciencedirect.com/science/article/pii/S2372770521000498

Bruton tyrosine kinase (BTK) inhibitor ibrutinib has been validated as an effective drug to treat B cell malignancies. Combined therapies comprising ibrutinib and anti-CD20 antibodies like rituximab were designed as a backbone in many clinical trials. However, the off-target inhibition of ibrutinib on interleukin-2 (IL-2)-inducible T cell kinase (ITK) may reduce rituximab’s antibody-dependent cellular cytotoxicity (ADCC) efficacy. Orelabrutinib (Orel), a novel BTK inhibitor, was designed with high selectivity to BTK. In our study, we demonstrated in preclinical models that orelabrutinib in combination with rituximab could preserve NK-cell-mediated ADCC induced by rituximab and enhanced the apoptosis of tumor cells in vitro. The addition of orelabrutinib to rituximab had produced promising combined anti-tumor effects in B cell lymphomas in vivo. Collectively, combination therapy of orelabrutinib with rituximab would benefit patients with B cell lymphoma, especially those with relapsed or refractory disease.