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

• DOI: 10.1016/j.omto.2021.03.015
• Publication Date: 2021-04-04T00:11:37Z
• Authors: Hui Yu; Xing Wang; Jiao Li; Yingying Ye; Dedao Wang; Wei Fang; Lan Mi; Ning Ding; Xiaogan Wang; Yuqin Song; Jun Zhu
• Keywords: anti-CD20 antibody; 0303 health sciences; 03 medical and health sciences; combined effects; BTK inhibitor; Neoplasms. Tumors. Oncology. Including cancer and carcinogens; Original Article; RC254-282; B cell lymphoma; 3. Good health

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.