The Evolving Use of Phosphatidylinositol 3-Kinase Inhibitors for the Treatment of Chronic Lymphocytic Leukemia

Benjamin L Lampson; Jennifer R Brown

doi:10.1016/j.hoc.2021.03.009

The Evolving Use of Phosphatidylinositol 3-Kinase Inhibitors for the Treatment of Chronic Lymphocytic Leukemia

Hematol Oncol Clin North Am. 2021 Aug;35(4):807-826. doi: 10.1016/j.hoc.2021.03.009. Epub 2021 May 27.

Authors

Benjamin L Lampson¹, Jennifer R Brown²

Affiliations

¹ Department of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, MA 02215, USA.
² Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, CLL Center, 450 Brookline Avenue, Boston, MA 02215, USA. Electronic address: jennifer_brown@dfci.harvard.edu.

Abstract

B cells express 4 phosphatidylinositol 3-kinase (PI3K) isoforms and have a dependence on p110δ for survival. The design of isoform-selective inhibitors is possible, and pharmacologic inhibition of p110δ is toxic to neoplastic chronic lymphocytic leukemia (CLL) cells for both cell-intrinsic and cell-extrinsic reasons. Idelalisib is a first-in-class p110δ inhibitor that exhibits efficacy for the treatment of relapsed CLL irrespective of adverse prognostic features. Duvelisib is a p110γ/δ inhibitor with a similar efficacy and safety profile to idelalisib. Recent data indicate that umbralisib, a p110δ/CK-1ε dual inhibitor, is safe and effective when administered to patients with CLL.

Keywords: Chronic lymphocytic leukemia; Duvelisib; Idelalisib; PI3-kinase inhibitors; Parsaclisib; Umbralisib; Zandelisib.

Publication types

Research Support, N.I.H., Extramural
Review

MeSH terms

Antineoplastic Agents* / therapeutic use
Humans
Leukemia, Lymphocytic, Chronic, B-Cell* / drug therapy
Phosphoinositide-3 Kinase Inhibitors / therapeutic use*

Substances

Antineoplastic Agents
Phosphoinositide-3 Kinase Inhibitors

Grants and funding

R01 CA213442/CA/NCI NIH HHS/United States