A review of the therapeutic role of the new third-generation TKI olverembatinib in chronic myeloid leukemia

Abstract

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Several tyrosine kinase inhibitors (TKIs) have been developed as targeted therapies to inhibit the oncogenic activity of several tyrosine kinases in chronic myeloid leukemia (CML), acute lymphoid leukemia (ALL), gastrointestinal stromal tumor (GIST), and other diseases. TKIs have significantly improved the overall survival of these patients and changed the treatment strategy in the clinic. However, approximately 50% of patients develop resistance or intolerance to imatinib. For second-generation TKIs, approximately 30%–40% of patients need to change therapy by 5 years when they are used as first-line treatment. Clinical study analysis showed that the T315I mutation is highly associated with TKI resistance. Developing new drugs that target the T315I mutation will address the dilemma of treatment failure. Olverembatinib, as a third-generation TKI designed for the T315I mutation, is being researched in China. Preliminary clinical data show the safety and efficacy in treating CML patients harboring the T315I mutation or who are resistant to first- or second-line TKI treatment. Herein, we review the characteristics and clinical trials of olverembatinib. We also discuss its role in the management of CML patients.

Keywords

• olverembatinib
• chronic myeloid leukemia
• tyrosine kinase inhibitors
• breakpoint cluster region protein and abelson tyrosine-protein kinase 1
• T315I mutation