Bruton Tyrosine Kinase Inhibitors in B-Cell Malignancies: Their Use and Differential Features

Declarations

Funding The preparation of this review was not supported by any external funding.

Authorship and Conflict of interest Matt Shirley is a salaried employee of Adis International Ltd/Springer Nature, is responsible for the article content and declares no relevant conflicts of interest.

Ethics approval, Consent to participate, Consent to publish, Availability of data and material, Code availability Not applicable.

Additional information about this Adis Drug Review can be found here.

Abstract

Starting with the first-in-class agent ibrutinib, the development of Bruton tyrosine kinase (BTK) inhibitors has led to dramatic improvements in the management of B-cell malignancies. Subsequently, more-highly selective second-generation BTK inhibitors (including acalabrutinib, zanubrutinib, tirabrutinib and orelabrutinib) have been developed, primarily with an aim to reduce off-target toxicities. More recently, third-generation agents including the non-covalent BTK inhibitors pirtobrutinib and nemtabrutinib have entered later-stage clinical development. BTK inhibitors have shown strong activity in a range of B-cell malignancies, including chronic lymphocytic leukaemia/small lymphocytic lymphoma, mantle cell lymphoma, Waldenström’s macroglobulinaemia and marginal zone lymphoma. The agents have acceptable tolerability, with adverse events generally being manageable with dosage modification. This review article summarises the evidence supporting the role of BTK inhibitors in the management of B-cell malignancies, including highlighting some differential features between agents.

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