Transient antagonism of anti-CD20 monoclonal antibodies and PI3K inhibitor idelalisib in DLBCL cell lines

Introduction: PI3K inhibitors are evaluated for relapsed and refractory Diffuse large B-cell lymphoma (DLBCL) patients.

Objective: As rituximab has shown to influence B-cell receptor (BCR) signaling, we investigated the interaction of anti-CD20 antibody rituximab and the new type II glycoengineered anti-CD20 antibody obinutuzumab in combination with the PI3K delta inhibitor idelalisib.

Methods: Established DLBCL cell lines were treated with either rituximab or obinutuzumab alone or in combination with PI3K delta inhibitor idelalisib.

Results: Rituximab and to a lesser extent obinutuzumab monotherapy resulted in a temporary upregulation of p-Akt, p42/44, and p38 signaling pathways. Idelalisib reduced p-Akt expression. Rituximab antagonized the p-Akt downregulation at early time points, while obinutuzumab did not interfere with idelalisib's effects. In cell growth analysis, early antagonism could also be detected.

Conclusion: The combination of idelalisib with CD antibodies shows an initial antagonism of rituximab but not obinutuzumab in downregulation of PI3K-signaling targets.