Selinexor, Venetoclax, and Dexamethasone in t(11;14)-Positive Relapsed/Refractory Multiple Myeloma (SELVEDge Study)

Background and Significance: Patients with multiple myeloma (MM) harboring translocation t(11;14) have been shown to benefit from the apoptosis-inducing drug venetoclax; however, the drug lacks FDA approval for the treatment of multiple myeloma thus far. Selinexor is an inhibitor of nuclear export that is FDA-approved for patients with multiple myeloma refractory to multiple lines of therapy. We recently reported that in four patients with multiple myeloma with t(11;14), the concomitant administration of venetoclax and selinexor was safe and associated with disease response (Nguyen et al. Nature Precision Oncology 2022). Moreover, the combination was synergistic in t(11;14) multiple myeloma cell lines and caused decreased levels of Cyclin D1 (which is overexpressed due to the CCND1-IGH fusion) when given in combination as compared to single agents ( Figure 1). These data suggested that the combination of venetoclax and selinexor is effective and t(11;14) may serve as a therapeutic marker for response and target for future clinical trials. We have therefore developed an investigator-initiated study of selinexor and venetoclax in patients with relapsed, refractory multiple myeloma harboring translocation t(11;14)- the SELVEDge study.