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Despite advances in therapies for B-cell lymphoma, patients may still develop resistance and often relapse. Contributing factors may include interactions between lymphoma cells (LCs) or leukemia cells and bone marrow microenvironment (BMM). Overexpression of CXCR4WT and its ligand CXCL12 promote LC-BMM interactions, contributing to disease severity in lymphomas or leukemia such as diffuse large B-cell lymphoma (DLBCL), chronic lymphocytic leukemia (CLL), follicular lymphoma (FL), and mantle cell lymphoma (MCL). Mavorixafor is an investigational oral CXCR4 antagonist being evaluated in combination with the Bruton tyrosine kinase (BTK) inhibitor ibrutinib in patients with Waldenström’s macroglobulinemia (WM). In preclinical models of MYD88L265P CXCR4WT WM, mavorixafor restored sensitivity of WM cells to B-cell-targeted therapies in coculture of WM cells and bone marrow stromal cells (BMSCs); however, the effects of mavorixafor on other lymphomas with CXCR4WT have not been evaluated. We report the effects of mavorixafor alone or in combination with B-cell─targeted therapies on LCs in an in vitro preclinical model and assess the role of BMM in the pathogenesis of B-cell lymphomas in an in vitro coculture model of LCs and BMSCs. Bioinformatic analysis of publicly available gene expression datasets GSE11318 and GSE32918 showed patients with DLBCL and CXCR4hi have significantly inferior survival probability compared with those with CXCR4low (P Citation Format: Tom Kruitwagen, Thalia Martins Rebelo, Barbara Maierhofer, Gerwin Heller, Halenya Monticelli, Arthur G. Taveras, Chi Nguyen. Mavorixafor enhances apoptosis of tumor cells treated with ibrutinib or venetoclax in diffuse large B-cell lymphoma, follicular lymphoma, mantle cell lymphoma, and chronic lymphocytic leukemia [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 5866. |
