Review of Bruton Tyrosine Kinase Inhibitors for the Treatment of Relapsed or Refractory Mantle Cell Lymphoma

Abstract

Mantle cell lymphoma (MCL) is a rare subtype of aggressive B-cell non-Hodgkin lymphoma that remains incurable with standard therapy. Patients typically require multiple lines of therapy, and those with relapsed or refractory (R/R) disease have a very poor prognosis. The Bruton tyrosine kinase (BTK) inhibitor ibrutinib has proven to be an effective agent for patients with R/R MCL. Although usually well tolerated, ibrutinib can be associated with unique toxicities, requiring discontinuation in some patients. Effective and well-tolerated alternatives to ibrutinib for patients with R/R MCL are therefore needed. Novel btk inhibitors such as acalabrutinib, zanubrutinib, and tirabrutinib are designed to improve on the safety and efficacy of first-generation btk inhibitors such as ibrutinib. Data from single-arm clinical trials suggest that, compared with ibrutinib, second-generation btk inhibitors have comparable efficacy and might have a more favourable toxicity profile. Those newer btk inhibitors might therefore provide a viable treatment option for patients with R/R MCL.