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

Autor: Nina Nguyen, Sana Chaudhry, Tulasigeri M. Totiger, Robert Diaz, Evan Roberts, Skye Montoya, Gabriel Pardo, Alejandro Pardo, Jumana Afaghani, Maurizio Affer, Jacob Jahn, Terrence Bradley, Francesco Maura, Dickran Kazandjian, Daniel Bilbao, Jennifer Chapman, Ola Landgren, James Hoffman, Justin Taylor
Jazyk: angličtina
Rok vydání: 2022
Předmět:
Zdroj: npj Precision Oncology, Vol 6, Iss 1, Pp 1-7 (2022)
Druh dokumentu: article
ISSN: 2397-768X
DOI: 10.1038/s41698-022-00315-2
Popis: Abstract 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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