Spotlight on ibrutinib and its potential in frontline treatment of chronic lymphocytic leukemia

Abstract

Chronic lymphocytic leukemia (CLL) is the most prevalent leukemia in the adult population. Current efforts are focused on better understanding the intricate pathophysiology of the disease to develop successful targeted therapies. Ibrutinib is emerging as an important agent in this new age of targeted treatment for CLL. As a Bruton’s tyrosine kinase inhibitor, it blocks the signaling pathway that malignant B-lymphocytes need for growth and maturation. Ibrutinib’s role in therapy was further expanded recently when the US Food and Drug Administration approved its use in both frontline and salvage treatment for patients with CLL. This review assesses the effectiveness of ibrutinib in the frontline setting, its efficacy in various types of patients with CLL, and its safety and tolerability.

Precision medicine and lymphoma

“…Running in tandem with efforts at exploiting genetic data for defining risk, access to genetic profiles are also pointing the way towards novel therapies. Ibrutinib, which inhibits the BTK enzyme responsible for propagating pro-survival signals from the BCR, which is constitutively active in ABC-DLBCLs (Figure 1) [36], has proved to be revolutionary in the treatment of chronic lymphocytic leukemia [37], and accumulating data suggest that it may be efficacious in poor-risk, BCR/NF-κBdependent ABC-DLBCL patients. In a Phase I/II trial of 80 patients, single agent ibrutinib was well tolerated and had an overall response rate (ORR) of 37% in ABC-DLBCL, compared to only 5% in GCB-DLBCL patients [36], and it is encouraging that all non-GCB patients achieved complete remission in a Phase I study examining ibrutinib in combination with rituximab-based chemotherapy [38].…”

Ibrutinib Therapy and Mycobacterium chelonae Skin and Soft Tissue Infection

“…We describe a patient who developed disseminated cutaneous M. chelonae infection while on ibrutinib, an irreversible oral inhibitor of Bruton’s tyrosine kinase (BTK) that is approved for the treatment of several B-cell malignancies. Since accelerated Food and Drug Administration approval in 2013, ibrutinib has revolutionized the treatment of CLL [ 5 , 6 ]. However, a growing concern is emerging as a result of increasing reports of opportunistic infections, particularly invasive fungal infections [ 7–9 ], which typically do not occur frequently in patients with BTK deficiency (X-linked agammaglobulinemia).…”

Unusual Relapse of Chronic Lymphocytic Leukemia After Remission

“…The treatment of relapsed CLL has been revolutionized with the advent of oral inhibitors of B-cell receptor (BCR) signal transduction [ 5 - 6 ]. Ibrutinib is one of the irreversible Bruton's tyrosine kinase (BTK) inhibitor, which leads to deactivation of microenvironment survival signaling and pro-survival pathways [ 7 ].…”