Targeting the B-cell receptor pathway: a review of current and future therapies for non-Hodgkin’s lymphoma

ABSTRACT

Introduction: The B-cell receptor (BCR) pathway is a crucial aspect of mature lymphocytes and is maintained in B-cell neoplasms. Many small module inhibitors targeting kinases within the BCR pathway are approved, with others in development, offering alternative treatment options to standard chemoimmunotherapy.

Areas covered: This review covers both approved inhibitors and investigational inhibitors of spleen tyrosine kinase (SYK), Bruton’s tyrosine kinase (BTK), and phosphoinositide-3-kinase (PI3K) in the treatment of B-cell lymphomas. To collect relevant articles, a literature search was completed through the use of PubMed and abstracts from ASH and ASCO national meetings. Search terms including non-Hodgkin lymphoma, and BCR inhibitors, as well as the individual drug names, were utilized. The majority of included studies are dated from 2012 to March 2018.

Expert opinion: BCR pathway inhibitors, such as ibrutinib and idelalisib, are novel treatments for non-Hodgkin lymphomas. While providing alternative treatment options to those with high-risk disease, poor functional status, and relapsed disease, outside of chronic lymphocytic leukemia (CLL), they have been limited to the relapsed/refractory setting. Their mechanisms of action, off/on-target effects, and resistance patterns create unique therapeutic dilemmas. It is our opinion that more specific inhibitors, as well as combination therapy, will define the future for BCR inhibitors.

KEYWORDS:

• Acalabrutinib
• Ibrutinib
• Idelalisib
• Copanlisib
• Phosphoinositide-3-kinase (PI3K)
• Bruton’s Tyrosine Kinase (BTK)
• Non-Hodgkin’s Lymphoma (NHL)
• B-Cell Receptor (BCR)
• Lymphoma

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties. A reviewer on this manuscript has disclosed honorarium from Epizyme, Roche, Sandoz, Legend, Abbvie and Novartis and research funding from Kite, Astra-Zeneca, Acerta, Celgene, Incyte, and Merck.

Additional information

Funding

This paper was not funded.