Ibrutinib in CLL/SLL: From bench to bedside (Review).

Abstract

B-cell receptor (BCR) signaling is important for the development and maturation of normal B-cells and plays a key role in B-cell malignancies. Bruton s tyrosine kinase (BTK), a crucial terminal kinase enzyme in BCR signaling, has emerged as an attractive target and has been successfully applied in the treatment of hematological malignancies. Ibrutinib, a BTK inhibitor, has demonstrated marked efficacy and tolerability in treatment-naïve, relapsed/refractory chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) and mantle cell lymphoma (MCL). Ibrutinib has been approved by the Food and Drug Administration (FDA) for the treatment of CLL/SLL, MCL, marginal zone lymphoma and Waldenström macroglobulinemia and by the China FDA for the treatment of CLL/SLL and MCL. Clinical trials of ibrutinib, as a single agent or combined with chemoimmunotherapy and other promising novel agents in the treatment of B-cell malignancy therapy, such as diffuse large B-cell lymphoma, follicular lymphoma, multiple myeloma, primary and secondary CNS lymphoma and acute lymphoblastic leukemia, T-cell lymphoma and myelodysplastic syndrome, are ongoing (https://clinicaltrials.gov/). The aim of the present review was mainly to cover the clinical developments regarding the use of ibrutinib in the treatment of CLL/SLL, as well as its safety and toxicity profile.