New and emerging Bruton tyrosine kinase inhibitors for treating mantle cell lymphoma - where do they fit in?

Despite recent prognostic improvements, mantle cell lymphoma (MCL) remains incurable. Bruton tyrosine kinase (BTK) is a key receptor in B-cell tumorigenesis, and the benefits of the first BTK inhibitor, ibrutinib, are becoming clear in MCL. However, off-target activities, which contribute to ibrutinib-related adverse events, suggest potential for further improvement of this drug class. Areas covered: The authors systematically interrogated ClinicalTrials.gov for trials containing keywords for BTK and MCL. Published literature for new and emerging BTK inhibitors being investigated in MCL was then identified (PubMed and Embase), summarized, and placed in the context of treatment guidelines. Expert commentary: Reduced off-target effects of new and emerging covalent, irreversible BTK inhibitors under investigation in patients with MCL offer the potential of improved safety compared with ibrutinib. Efficacy may also be favorable based on trial data for acalabrutinib, which has just been approved in the USA as second-line therapy for MCL. The role of BTK inhibitors in treating MCL will evolve substantially over the coming years as results from a number of trials become available, particularly in relation to potential upfront use and possible synergy with other targeted therapies such as B-cell lymphoma 2, phosphoinositide 3-kinase and checkpoint inhibitors.