A review of the mechanism of action, safety, and efficacy of selinexor in multiple myeloma

Abstract

In recent years, the armamentarium of routinely available treatments for relapsed and/or refractory multiple myeloma (RRMM) in Canada has dramatically expanded, but treatment gaps still exist. In early relapse (1-3 prior lines), monoclonal antibody (mAb) combinations on a backbone of lenalidomide or bortezomib (e.g. DRd, DVd) have been the mainstay, with combinations building on second generation backbones such as pomalidomide and carfilzomib (e.g. PCd, PVd, Kd) largely reserved for later relapse (after 2 prior lines). However, the increasing use of multi-class drug combinations in the frontline (e.g. DRd, RVd) and a shift towards ongoing therapy until progression, renders patients heavily drug-exposed and refractory at time of early relapse, needful of treatments with novel mechanisms of action. Selinexor is poised to fill an unmet need with a unique, non-overlapping mechanism of action to other available agents. XPOVIO® (selinexor) is indicated in combination with bortezomib and dexamethasone for the treatment of adult patients with multiple myeloma who have received at least one prior therapy. SVd received Health Canada approval May 31, 2022. This review will present data on selinexor’s mechanism of action, efficacy in combination with dexamethasone and bortezomib (Sd, SVd), dosing and scheduling, as well as the management of its common and distinct toxicities.