The preclinical discovery and development of orelabrutinib as a novel treatment option for B-cell lymphoid malignancies

Bruton's tyrosine kinase (BTK) inhibitors have recently been approved for clinical use against several B-cell indolent lymphoid malignancies, both as single agents or in combination. One second-generation BTK inhibitor that is being developed for the treatment of B-cell hematological malignancies, as well as for autoimmune disorders, is orelabrutinib.This paper reviews recent developments in the use of orelabrutinib against B-cell indolent lymphoid malignancies such as chronic lymphocytic leukemia, mantle cell lymphoma, diffuse large B-cell lymphoma, Waldenstrom macroglobulinemia and central nervous system lymphoma. Google Scholar and PubMed were initially searched for articles, and the corpus of articles was broadened by reviewing the references of the identified papers. All were in English. The corpus comprised papers from 2016 to April 2023. In addition, a manual search was performed of conference proceedings from the last five years of The American Society of Hematology, American Society of Clinical Oncology and the European Hematology Association.Orelabrutinib is an active drug in indolent and aggressive B-cell lymphoid malignancies. It demonstrates high selectivity, good efficacy and an excellent safety profile. Nevertheless, further clinical trials are required to optimize its use. In addition, several other highly selective BTK inhibitors are being examined in early-phase studies.