Bruton Tyrosine Kinase Inhibitors for the Frontline Treatment of Chronic Lymphocytic Leukemia

Chronic lymphocytic leukemia (cll) is the most commonly diagnosed adult leukemia in Canada. Biologic heterogeneity of cll between patients results in variable disease trajectories and responses to therapy. Notably, compared with patients lacking high-risk features, those with such features—such as deletions in chromosome 17p, aberrations in the TP53 gene, or unmutated immunoglobulin heavy chain variable region genes—experience inferior outcomes and responses to standard chemoimmunotherapy. Novel agents that target the B cell receptor signalling pathway, such as Bruton tyrosine kinase (btk) inhibitors, have demonstrated clinical efficacy and safety in patients with treatment-naïve cll, particularly those with high-risk features. However, given the current lack of head-to-head trials comparing btk inhibitors, selection of the optimal btk inhibitor for patients with cll is unclear and requires consideration of multiple factors. In the present review, we focus on the efficacy, safety, and pharmacologic features of the btk inhibitors that are approved or under clinical development, and we discuss the practical considerations for the use of those agents in the Canadian treatment landscape.