Selecting the optimal BTK inhibitor therapy in CLL: rationale and practical considerations

Bruton’s tyrosine kinase (BTK) inhibitors have dramatically changed the treatment of newly diagnosed and relapsed/refractory chronic lymphocytic leukemia (CLL). Ibrutinib, acalabrutinib, and zanubrutinib are Food and Drug Administration (FDA)-approved BTK inhibitors that have all demonstrated progression-free survival (PFS) benefit compared with chemoimmunotherapy. The efficacy of these agents compared to one another is under study; however, current data suggest they provide similar efficacy. Selectivity for BTK confers different adverse effect profiles, and longer follow-up and real-world use have characterized side effects over time. The choice of BTK inhibitor is largely patient-specific, and this review aims to highlight the differences among the agents and guide the choice of BTK inhibitor in clinical practice.