Abstract 1061: Characterization of synergistic selinexor combinations with dexamethasone, pomalidomide, elotuzumab, and daratumumab in primary MM cells
Introduction. Multiple myeloma (MM) is an all but incurable plasma cell malignancy without predictive biomarkers for approved therapies. Selinexor (SELI), a nuclear export inhibitor targeting exportin 1 (XPO1), is approved with dexamethasone (DEX) with promising SELI-combination studies ongoing. We investigated SELI combinations ex vivo to identify synergistic combinations and companion biomarkers. Methods. We established a platform to perform parallel RNA/exome sequencing and ex vivo drug sensitivity assessment on CD138+ cells from MM patient bone marrow aspirates. At the time of this analysis, 844 different samples with clinical, WES and RNA sequencing data were treated ex vivo with the following agents: SELI (n=75), DEX (192), pomalidomide (POM, 268), elotuzumab (ELO, 21), daratumumab (DARA, 117), SELI+DEX (22), SELI+POM (20), SELI+ELO (21), SELI+DARA (27). Cells were cultured with autologous macrophages, stroma, collagen matrix and patient-derived serum. Cell death (LD50 and AUC) was assessed through digital image analysis. Sequencing was performed through ORIEN/AVATAR. Links between non-synonymous mutations in coding genes and cell death were calculated using T-tests with multiple test correction. Results. Our analysis identified SELI+DEX (number of samples=60, pCitation Format: Praneeth Reddy Sudalagunta, Mark B. Meads, Rafael Renatino Canevarolo, Maria Coelho Silva, Christopher Cubitt, Gabriel DeAvila, Raghunandan Reddy Alugubelli, Constantine N. Logothetis, Amit Kulkarni, Qi Zhang, Oliver Hampton, Christopher J. Walker, Yosef Landesman, Kenneth Shain, Ariosto Siqueira Silva. Characterization of synergistic selinexor combinations with dexamethasone, pomalidomide, elotuzumab, and daratumumab in primary MM cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 1061.