Clinical use of PI3K inhibitors in B-cell lymphoid malignancies: today and tomorrow

ABSTRACT

Introduction: PI3K inhibitors are an important new therapeutic option for the treatment of relapsed and refractory B-cell lymphoid malignancies. Idelalisib is a PI3Kδ inhibitor that has been approved for the treatment of lymphoma and chronic lymphocytic leukemia in the relapsed/refractory setting, and several other PI3K inhibitors are being developed targeting other isoforms of the PI3K enzyme, which results in distinct toxicities and variable efficacy in the clinical setting.

Areas covered: We provide a general overview of PI3K inhibitors, recommended applications, and the mechanism and management of toxicities. We further review trials, ongoing and completed, leading to the approval of idelalisib as well other PI3K inhibitors currently in development. Articles were obtained from PubMed, and abstracts were searched for the past 5 years from the websites for ASCO, ASH, EHA, and ICML/Lugano.

Expert commentary: PI3K inhibitors provide an important and powerful pharmacologic tool in the armamentarium against hematologic malignancies, especially for relapsed/refractory B-cell lymphoid malignancies. Unique toxicities are associated with inhibition of different isoforms of the PI3K enzyme, as demonstrated with the infectious and autoimmune toxicities associated with the PI3Kδ inhibitor, idelalisib. Due to these unique toxicities, PI3K inhibitors should only be used in formally approved combinations and settings.

KEYWORDS:

• PI3K inhibitor
• lymphoma
• non-Hodgkin’s lymphoma
• clinical trial
• toxicity
• autoimmune
• infection
• idelalisib

Declaration of interest

J Cohen has had research funding from Bristol-Myers Squibb, Novartis, Millennium/Takeda, Pharmacyclics, Seattle

Genetics, Infinity, Abbvie, Celgene, LRF, ASH. K Blum has had research funding from Celgene, Novartis, BMS, Constellation Pharmaceuticals, Millennium, Janssen,

Morphosys, NCI. The authors have no other 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 apart from those disclosed.

supplemental data

The supplemental data for this article can be accessed here.

Additional information

Funding

This article was not funded.