Addition of BTK inhibitor Orelabrutinib to Rituximab improved anti-tumor effects in B cell lymphoma

Abstract 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 IL2-inducible T-cell kinase (ITK) may reduce rituximab’s 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 antibody-dependent cellular cytotoxicity (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.