Introduction: The covalent Bruton's tyrosine kinase (BTK) inhibitor ibrutinib has been approved in the USA for B cell malignancies for almost ten years and has improved the survival of patients with chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL). Orelabrutinib is a novel, highly selective covalent BTK inhibitor with proven efficacy and acceptable safety profile. In 2020, it was approved for the treatment of relapsed/refractory (R/R) CLL/SLL in China.
Areas covered: In this review, we summarized the current clinical trials exploring orelabrutinib monotherapy or orelabrutinib-based combination regimens in CLL/SLL, especially R/R CLL/SLL. Pharmacodynamics, pharmacokinetics, clinical efficacy and safety of orelabrutinib are also discussed.
Expert opinion: Orelabrutinib selectively inhibits BTK via covalent binding and exhibits linear pharmacokinetics. BTK is the only kinase targeted by orelabrutinib, and a few off-target toxicities of orelabrutinib have been reported. The phase I/II trial demonstrated the efficacy and safety of orelabrutinib in patients with R/R CLL/SLL; however, further clinical trials are needed to compare orelabrutinib with ibrutinib in patients with R/R CLL/SLL and to evaluate its efficacy and safety in patients with treatment-naive CLL/SLL.
Keywords: Orelabrutinib; bruton’s tyrosine kinase; chronic lymphocytic leukemia; inhibitor; relapsed/refractory; small lymphocytic lymphoma.