Combination venetoclax and selinexor effective in relapsed refractory multiple myeloma with translocation t(11;14)

Patients with multiple myeloma-bearing translocation t(11;14) have recently been shown to benefit from the apoptosis-inducing drug venetoclax; however, the drug lacks FDA approval in multiple myeloma thus far due to a potential safety signal in the overall patient population. Selinexor is an inhibitor of nuclear export that is FDA-approved for patients with multiple myeloma refractory to multiple lines of therapy. Here, we report 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. 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. These data suggest 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.

Automated summary

In this study, the safety and therapeutic effects of simultaneous administration of venetoclax and selinexor in patients with t(11;14) multiple myeloma were reported. The combination showed synergistic effects in t(11;14) multiple myeloma cell lines and resulted in decreased levels of Cyclin D1. These findings suggest that the combination of venetoclax and selinexor may be a promising approach for the treatment of multiple myeloma.