Selinexor for the treatment of patients with relapsed or refractory multiple myeloma

J Oncol Pharm Pract. 2024 Apr;30(3):535-546. doi: 10.1177/10781552241235902. Epub 2024 Mar 8.

Abstract

Objective: Multiple myeloma cells resist standard therapies due to overexpression of the transport protein, exportin 1. Selinexor is a novel drug that targets the Exportin 1 protein in these cells.

Data source: A comprehensive search was done, and data showing the efficacy and safety of selinexor in relapsed/refractory multiple myeloma was collected using PubMed, Google Scholar, and clincialtrials.gov.

Data summary: Results from the clinical trials STORM, BOSTON, and STOMP were included. Parts I and II of the STORM trial revealed a progression-free survival (PFS) of 4.7 and 3.7 months, a median duration of response of 6.2 and 4.4 months, and an overall survival of 7.3 and 8.4 months, respectively. BOSTON trial's SVd arm (selinexor, bortezomib, and dexamethasone) had a median follow-up period of 13.2 months and an mPFS of 13.93 months. The Vd arm (bortezomib and dexamethasone) had a median follow-up duration of 16.5 months and an mPFS of 9.46 months. The STOMP trial is still active and has limited data available. The SKd arm (selinexor, carfilzomib, and dexamethasone) reported an overall response rate of 66.7% in patients with triple refractory multiple myeloma, and 82% in patients with high-risk cytogenetics. The SPd arm (selinexor, pomalidomide, and dexamethasone) shows an overall response rate of 54.30% in pomalidomide naïve-nonrefractory, 35.70% in pomalidomide refractory and 60% in those dosed at RP2D. SRd arm (selinexor, lenalidomide, and dexamethasone) shows an overall response rate of 91.7% in lenalidomide naïve and 12.5% in lenalidomide refractory patients. SVd (selinexor, bortezomib, and dexamethasone) arm reported an overall response rate of 63% in all patients while the SDd arm (selinexor, daratumumab, and dexamethasone) showed an overall response rate of 73%.

Conclusion: To improve the outcome of patients with relapsed/refractory multiple myeloma, it is critical to develop new therapies, assess potential therapeutic synergies, and overcome drug resistance by determining the efficacy of multiple myeloma therapies across multiple disease subgroups.

Keywords: Selinexor; exportin 1; multiple myeloma; refractory multiple myeloma.

Publication types

  • Review

MeSH terms

  • Antineoplastic Agents / therapeutic use
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Bortezomib / therapeutic use
  • Dexamethasone / therapeutic use
  • Drug Resistance, Neoplasm
  • Exportin 1 Protein
  • Humans
  • Hydrazines* / therapeutic use
  • Karyopherins / antagonists & inhibitors
  • Multiple Myeloma* / drug therapy
  • Neoplasm Recurrence, Local / drug therapy
  • Progression-Free Survival
  • Receptors, Cytoplasmic and Nuclear
  • Triazoles* / therapeutic use

Substances

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