Journal
NPJ PRECISION ONCOLOGY
Volume 6, Issue 1, Pages -Publisher
NATURE PORTFOLIO
DOI: 10.1038/s41698-022-00315-2
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Funding
- American Society of Hematology
- National Institutes of Health [1K08CA230319]
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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.
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.
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