TY - JOUR
T1 - Selinexor for the treatment of multiple myeloma
AU - Podar, Klaus
AU - Shah, Jatin
AU - Chari, Ajai
AU - Richardson, Paul G
AU - Jagannath, Sundar
N1 - Funding Information:
K Podar has received speaker’s honoraria from Celgene, Amgen Inc. and Janssen Pharmaceuticals as well as consultancy fees from Celgene, Takeda and Janssen Pharmaceuticals. He has also received research support from Roche Pharmaceuticals. A. Chari received grant support and consulting fees from Millennium/Takeda, grant support, advisory board fees, and consulting fees from Celgene, Novartis Pharmaceuticals, Amgen, and Janssen, and consulting fees from Bristol-Myers Squibb. A Chari has received advisory board fees from Sanofi and Oncopeptides, grant support from Pharmacyclics, and grant support and advisory board fees from Seattle Genetics. P Richardson has received grant support and honoraria from Oncopeptides, Celgene, and Takeda, grant support from Bristol-Myers Squibb, and honoraria from Amgen, Janssen, and Karyopharm Therapeutics. S Jagannath has received advisory board fees and consulting fees from Celgene, Bristol-Myers Squibb, Janssen Pharmaceuticals and Merck & Co. Finally, J Shah is employed by Karyopharm Therapeutics. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.
Publisher Copyright:
© 2020, © 2020 Informa UK Limited, trading as Taylor & Francis Group.
PY - 2020/3/3
Y1 - 2020/3/3
N2 - Introduction: Despite unprecedented advances in the treatment of multiple myeloma (MM), almost all patients develop a disease that is resistant to the five most commonly used and active anti-MM agents. The prognosis for this patient population is particularly poor resulting in an unmet need for additional therapeutic options. Exportin-1 (XPO-1) is a major nuclear export protein of macromolecular cargo frequently overexpressed in MM. Selinexor is a first-in-class, oral Selective-Inhibitor-of-Nuclear-Export (SINE) compound that impedes XPO-1. Based on results of the STORM-trial, selinexor in combination with dexamethasone was granted accelerated FDA approval for patients with penta-refractory MM in July 2019.Areas covered: This article summarizes our up-to-date knowledge on the pathophysiologic role of XPO-1 in MM. Furthermore, it reviews the most recent clinical data on selinexor in combination with dexamethasone and other anti-MM agents; and discusses its safety profile, management strategies; and potential future developments.Expert opinion: Selinexor represents a next-generation-novel agent with an innovative mechanism of action that marks a significant advance in the treatment of heavily pretreated MM patients. Ongoing studies investigate its therapeutic potential also in earlier lines of therapy. Additional data is needed to confirm that selinexor and other SINE compounds are a valuable addition to our current therapeutic armamentarium.
AB - Introduction: Despite unprecedented advances in the treatment of multiple myeloma (MM), almost all patients develop a disease that is resistant to the five most commonly used and active anti-MM agents. The prognosis for this patient population is particularly poor resulting in an unmet need for additional therapeutic options. Exportin-1 (XPO-1) is a major nuclear export protein of macromolecular cargo frequently overexpressed in MM. Selinexor is a first-in-class, oral Selective-Inhibitor-of-Nuclear-Export (SINE) compound that impedes XPO-1. Based on results of the STORM-trial, selinexor in combination with dexamethasone was granted accelerated FDA approval for patients with penta-refractory MM in July 2019.Areas covered: This article summarizes our up-to-date knowledge on the pathophysiologic role of XPO-1 in MM. Furthermore, it reviews the most recent clinical data on selinexor in combination with dexamethasone and other anti-MM agents; and discusses its safety profile, management strategies; and potential future developments.Expert opinion: Selinexor represents a next-generation-novel agent with an innovative mechanism of action that marks a significant advance in the treatment of heavily pretreated MM patients. Ongoing studies investigate its therapeutic potential also in earlier lines of therapy. Additional data is needed to confirm that selinexor and other SINE compounds are a valuable addition to our current therapeutic armamentarium.
KW - Active Transport, Cell Nucleus/drug effects
KW - Antineoplastic Combined Chemotherapy Protocols/administration & dosage
KW - Cell Line, Tumor
KW - Cell Nucleus/drug effects
KW - Clinical Trials as Topic
KW - Dexamethasone/therapeutic use
KW - Drug Evaluation, Preclinical
KW - Humans
KW - Hydrazines/administration & dosage
KW - Karyopherins/antagonists & inhibitors
KW - Multiple Myeloma/drug therapy
KW - Prognosis
KW - Receptors, Cytoplasmic and Nuclear/antagonists & inhibitors
KW - Triazoles/administration & dosage
KW - Multiple myeloma
KW - selective inhibitor of nuclear export (sine) compounds
KW - penta-refractoriness
KW - exportin-1
UR - http://www.scopus.com/inward/record.url?scp=85078320845&partnerID=8YFLogxK
U2 - 10.1080/14656566.2019.1707184
DO - 10.1080/14656566.2019.1707184
M3 - Review article
C2 - 31957504
SN - 1465-6566
VL - 21
SP - 399
EP - 408
JO - Expert Opinion on Pharmacotherapy
JF - Expert Opinion on Pharmacotherapy
IS - 4
ER -