Selinexor: A First-in-Class Nuclear Export Inhibitor for Management of Multiply Relapsed Multiple Myeloma

Ann Pharmacother. 2020 Jun;54(6):577-582. doi: 10.1177/1060028019892643. Epub 2019 Dec 2.

Abstract

Objective: To review the pharmacology, pharmacokinetics, efficacy, and safety of selinexor for management of relapsed multiple myeloma (MM). Data Sources: A literature search was performed of PubMed and MEDLINE databases (January 1, 2000, to November 14, 2019), abstracts from the American Society of Hematology and the American Society of Clinical Oncology, and ongoing studies from US National Institutes of Health ClinicalTrials.gov. Queries were performed using key words selinexor, SINE, XPO1, and Xpovio. Study Selection/Data Extraction: Human and animal studies related to the pharmacology, pharmacokinetics, efficacy, and safety of selinexor were identified. Data Synthesis: Although numerous advances have been made in MM management, there remains an unmet need for treatment of heavily relapsed/refractory disease. Selinexor is a first-in-class selective inhibitor of nuclear export, which, through inhibition of exportin-1, causes accumulation of tumor suppressor proteins, reduction in oncoproteins, and apoptosis of plasma cells. Selinexor exhibited an overall response in 26% of patients with multiply relapsed MM. Median progression-free survival was 3.7 months, and overall survival was 8.6 months. Common adverse effects include thrombocytopenia, neutropenia, fatigue, and nausea. Ongoing studies are investigating combination therapies utilizing selinexor. Relevance to Patient Care and Clinical Practice: This review describes the efficacy, safety, and clinical applicability of selinexor, a novel agent with potential to meet an unmet need in refractory MM. Conclusion: Selinexor has demonstrated activity in a heavily refractory patient population. Given the adverse effect profile and associated costs, additional studies are needed to further elucidate the appropriate clinical scenario and combinations for selinexor use.

Keywords: clinical pharmacy; hematology; multiple myeloma; oncology; pharmacology.

Publication types

  • Review

MeSH terms

  • Active Transport, Cell Nucleus / drug effects
  • Animals
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / pharmacokinetics
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Cell Nucleus / drug effects*
  • Cell Nucleus / metabolism
  • Female
  • Humans
  • Hydrazines / administration & dosage
  • Hydrazines / adverse effects
  • Hydrazines / pharmacokinetics
  • Hydrazines / therapeutic use*
  • Karyopherins / antagonists & inhibitors*
  • Male
  • Multiple Myeloma / drug therapy*
  • Multiple Myeloma / metabolism
  • Multiple Myeloma / pathology
  • Plasma Cells / drug effects*
  • Plasma Cells / metabolism
  • Plasma Cells / pathology
  • Receptors, Cytoplasmic and Nuclear / antagonists & inhibitors*
  • Recurrence
  • Triazoles / administration & dosage
  • Triazoles / adverse effects
  • Triazoles / pharmacokinetics
  • Triazoles / therapeutic use*

Substances

  • Hydrazines
  • Karyopherins
  • Receptors, Cytoplasmic and Nuclear
  • Triazoles
  • exportin 1 protein
  • selinexor