Combination Venetoclax and Selinexor Effective in Relapsed Refractory Multiple Myeloma with Translocation T(11;14)

Overview

Journal NPJ Precis Oncol

Publisher Springer Nature

Specialty Oncology

Date 2022 Oct 19

PMID 36261486

Authors

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

Affiliations

Soon will be listed here.

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.

Citing Articles

XPO1/Exportin-1 in Acute Myelogenous Leukemia; Biology and Therapeutic Targeting.

Bruserud O, Selheim F, Hernandez-Valladares M, Reikvam H Biomolecules. 2025; 15(2).

PMID: 40001478 PMC: 11852384. DOI: 10.3390/biom15020175.

Venetoclax in the treatment of secondary plasma cell leukemia with translocation t(11;14): a case report and literature review.

Elsabah H, Ghasoub R, El Omri H, Benkhadra M, Cherif H, Y Taha R Front Oncol. 2024; 14:1390747.

PMID: 39050574 PMC: 11266074. DOI: 10.3389/fonc.2024.1390747.

Treatment of multiple myeloma with selinexor: a review.

Huang Q, Zhao R, Xu L, Hao X, Tao S Ther Adv Hematol. 2024; 15:20406207231219442.

PMID: 38186637 PMC: 10771077. DOI: 10.1177/20406207231219442.

Mechanisms of action of the BCL-2 inhibitor venetoclax in multiple myeloma: a literature review.

Cao Q, Wu X, Zhang Q, Gong J, Chen Y, You Y Front Pharmacol. 2023; 14:1291920.

PMID: 38026941 PMC: 10657905. DOI: 10.3389/fphar.2023.1291920.

Effective venetoclax-based treatment in relapsed/refractory multiple myeloma patients with translocation t(6;14).

Cegledi A, Csukly Z, Fekete M, Kozma A, Szemlaky Z, Andrikovics H Pathol Oncol Res. 2023; 29:1611375.

PMID: 38025905 PMC: 10668022. DOI: 10.3389/pore.2023.1611375.

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