Selinexor in multiple myeloma

Expert Opin Pharmacother. 2024 Mar;25(4):421-434. doi: 10.1080/14656566.2024.2333376. Epub 2024 Mar 25.

Abstract

Introduction: Selinexor, an XPO1 inhibitor, has emerged as a promising therapeutic option in the challenging landscape of relapsed/refractory multiple myeloma (RRMM).

Areas covered: This article provides a review of selinexor, with a focus on available clinical studies involving MM patients and its safety profile. Clinical trials, such as STORM and BOSTON, have demonstrated its efficacy, particularly in combination regimens, showcasing notable overall response rates (ORR) and prolonged median progressionfree survival (mPFS). Selinexor's versatility is evident across various combinations, including carfilzomibdexamethasone (XKd), lenalidomidedexamethasone (XRd), and pomalidomidedexamethasone (XPd), with efficacy observed even in tripleclass refractory and highrisk patient populations. However, challenges, including resistance mechanisms and adverse events, necessitate careful management. Realworld evidence also underscores selinexor's effectiveness in RRMM, though dose adjustments and supportive measures remain crucial. Ongoing trials are exploring selinexor in diverse combinations and settings, including pomalidomidenaïve patients and postautologous stem cell transplant (ASCT) maintenance.

Expert opinion: The evolving landscape of selinexor's role in the sequencing of treatment for RRMM, its potential in highrisk patients, including those with extramedullary disease, as revealed in the most recent international meetings, and ongoing investigations signal a dynamic era in myeloma therapeutics. Selinexor emerges as a pivotal component in multidrug strategies and innovative combinations.

Keywords: MM; Selinexor; XPO1; therapy.

Publication types

  • Review

MeSH terms

  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Exportin 1 Protein
  • Humans
  • Hydrazines* / adverse effects
  • Hydrazines* / therapeutic use
  • Karyopherins / antagonists & inhibitors
  • Multiple Myeloma* / drug therapy
  • Progression-Free Survival
  • Receptors, Cytoplasmic and Nuclear / antagonists & inhibitors
  • Triazoles* / adverse effects
  • Triazoles* / therapeutic use

Substances

  • selinexor
  • Hydrazines
  • Triazoles
  • Karyopherins
  • Exportin 1 Protein
  • Receptors, Cytoplasmic and Nuclear
  • Antineoplastic Agents