Application progress of novel Bruton tyrosine kinase inhibitors in B-cell lymphoma

Abstract

The Bruton tyrosine kinase (BTK) inhibitor ibrtinib has excellent results in B-cell lymphoma. However, there are still unmet treatment needs in clinical practice. New BTK inhibitors are highly selective and specific, reducing off-target effects. The overall response rate (ORR) of acalabrutinib combination therapy is more than 90%, and high rates of peripheral blood and bone marrow minimal residual disease (MRD)-negative are obtained. Orelabrutinib is a new domestic BTK inhibitor, the results of a phase Ⅱ study showed that the ORR in relapsed/refractory chronic lymphocytic leukemia/small lymphocytic lymphoma is 88.5%, and in mantle cell lymphoma is 82.5%. Another new domestic BTK inhibitor zanubrutinib, international multi-center study showed that ORR is 95.9% in relapsed/refractory CLL, and in treatment-naive chronic lymphocytic leukemia with del (17p) is 92.2%. In addition, non-covalent BTK inhibitors are also emerging, which are expected to overcome the problem of resistance to BTK inhibitors. Key words: Lymphoma, B-cell; Protein-tyrosine kinases; Protein kinase inhibitors; Bruton tyrosine kinase