Abstract 2033: Testing the combined effects of low dose olaparib plus ibrutinib on MCL cytotoxicity

Abstract

Abstract Mantle cell lymphoma (MCL) presents a therapeutic challenge, with frequent relapses after therapy due to high levels of DNA damage and disease evolution. One currently approved MCL therapeutic, ibrutinib, is a tissue-specific agent with relatively few adverse effects. However, ibrutinib is administered at high dose for MCL and provides only a short progression-free survival time. To potentially improve ibrutinib therapy for MCL, we tested the effects of combining ibrutinib with the DNA damage response inhibitor, olaparib, on MCL cells in vitro. We confirmed that ibrutinib monotherapy is cytotoxic to MCL cell lines only at high doses (> 25 μM). In contrast, single-agent olaparib treatment is cytotoxic at lower concentrations (10 μM). Importantly, the addition of low dose olaparib to ibrutinib has an additive cytotoxic effect. Notably, the effects of ibrutinib alone and in combination are dependent on cell medium composition. Our findings support clinical testing of ibrutinib plus olaparib therapy to reduce MCL cell burden initially and to potentially slow MCL cell evolution in the longer term. Our data also suggest the possibility for more effective ibrutinib-based therapy via manipulation of the MCL cell niche. Citation Format: Adam D. Curtis, Todd A. Hoffert, Sheila S. Rajan, Jens Rueter, Lindsay S. Shopland. Testing the combined effects of low dose olaparib plus ibrutinib on MCL cytotoxicity [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 2033. doi:10.1158/1538-7445.AM2017-2033