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Clinical Utility of Selinexor/Dexamethasone in Patients with Relapsed or Refractory Multiple Myeloma: A Review of Current Evidence and Patient Selection

Authors Malandrakis P, Ntanasis-Stathopoulos I, Gavriatopoulou M, Terpos E

Received 2 May 2020

Accepted for publication 21 June 2020

Published 1 July 2020 Volume 2020:13 Pages 6405—6416


Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 2

Editor who approved publication: Prof. Dr. Geoffrey Pietersz

Panagiotis Malandrakis,* Ioannis Ntanasis-Stathopoulos,* Maria Gavriatopoulou, Evangelos Terpos

Department of Clinical Therapeutics, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece

*These authors contributed equally to this work

Correspondence: Evangelos Terpos
Department of Clinical Therapeutics, School of Medicine, National and Kapodistrian University of Athens, Alexandra General Hospital, 80 Vas. Sofias Avenue, Athens 11528, Greece
Tel +30-213-216-2846
Fax +30-213-216-2511

Abstract: Multiple myeloma (MM) is one the most common hematological malignancies, and despite the survival prolongation offered by proteasome inhibitors (PIs), immunomodulatory drugs (IMiDs) and anti-CD38 monoclonal antibodies, the need for novel agents is prominent. Selinexor is a first-in-class, oral, selective inhibitor of exportin-1 (XPO1), a vital protein for the exportation of more than 200 tumor suppressor proteins from the nucleus. Both in solid tumors and hematologic malignancies, selinexor-mediated inhibition of nucleus export seems to effectively lead to cancer cell death. Selinexor in combination with dexamethasone (Sd) received an accelerated FDA approval on July 2019 for heavily pretreated patients with relapsed/refractory MM (RRMM) based on the promising results of the Phase II STORM trial. The preliminary results of the randomized Phase III BOSTON trial have shown a 47% increase in progression-free survival among PI-sensitive, RRMM patients who received selinexor with bortezomib-dexamethasone compared with bortezomib-dexamethasone alone. Several different selinexor-containing triplet regimens are currently being tested in the RRMM setting in an umbrella trial, and the preliminary results seem promising. Furthermore, the addition of selinexor in other anti-myeloma agents seems to overcome drug-acquired resistance in preclinical studies. The main toxicities of selinexor are gastrointestinal disorders and hematologic toxicities (mainly thrombocytopenia); however, they are manageable with proper supportive measures. In conclusion, selinexor is a new anti-myeloma drug that seems to be effective in patients who have no other therapeutic options, including patients who have received novel cellular therapies such as CAR-T cells. Its potential role earlier in the therapeutic algorithm of MM is currently under clinical investigation.

Keywords: selinexor, exportin, selective inhibitor of nuclear export, relapsed/refractory, myeloma

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