Ibrutinib in Chronic Lymphocytic Leukemia: Clinical Applications, Drug Resistance, and Prospects

Bruton’s tyrosine kinase (BTK), a pivotal component of B-cell receptor (BCR) signaling, has been recognized as an important driver of the pathogenesis of chronic lymphocytic leukemia. Ibrutinib is a highly active and selectively irreversible inhibitor of BTK, which has been approved to be effective in both frontline and recurrent therapy of CLL. Acquired resistance has become a greater problem than initially anticipated with the widespread use of ibrutinib. An ongoing exploration of the mechanisms of ibrutinib resistance (IR) in CLL has revealed potentially useful therapeutic targets. New drugs expected to overcome IR in CLL are in the early stages of clinical development. This study aimed to summarize the possible mechanisms of IR and retrospectively analyze promising therapies that might have superior efficacy in overcoming IR.