Abstract 2366: Targeting PI3 pathway in ibrutinib resistant diffuse large B-cell lymphoma

Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of non-Hodgkin lymphoma (NHL) and approximately 30% of patients with DLBCL develop relapsed/refractory disease that becomes a major cause of mortality and morbidity. The Bruton kinase (BTK) inhibitor ibrutinib successfully blocks B-cell receptor signaling and shows clinical benefit in leukemia and lymphomas, including mantle cell lymphoma (MCL) and DLBCL. Ibrutinib elicits overall desirable response rate with relapsed/refractory MCL and ABC DLBCL. However, in spite of these encouraging results, responses are variable and generally incomplete, acquired resistance is common, and recurrence and persistence of lymphoma is a problem. We undertook a study of factors underlying acquired ibrutinib resistance (IR) in initially ibrutinib-sensitive DLBCL cell lines. In this study, IR DLBCL cell lines were generated by continuous culturing of parental (PT) cell lines in increasing concentrations of ibrutinib. Once established, IR cell lines were removed from ibrutinib, expanded, and cultured under the same conditions as the PT cell lines for further experiments. Of 5 ABC DLBCL cell lines tested, two (OCI-LY3, U2932) were initially resistant to ibrutinib (IC 50 >10µM).Three (TMD8, OCI-LY10, HBL1) were sensitive (IC 50 Note: This abstract was not presented at the meeting. Citation Format: Neeraj Jain, Lalit Sehgal, Stephen Joseph Shuttleworth, Felipe Samaniego. Targeting PI3 pathway in ibrutinib resistant diffuse large B-cell lymphoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2366. doi:10.1158/1538-7445.AM2017-2366