selinexor + carfilzomib + dexamethasone

This is a **three-drug combination regimen** consisting of **selinexor** (an oral, first-in-class selective inhibitor of nuclear export [SINE] compound targeting exportin 1 [XPO1]), **carfilzomib** (a second-generation proteasome inhibitor), and **dexamethasone** (a synthetic glucocorticoid corticosteroid)[3][6][2]. **Mechanism of action**: - **Selinexor** blocks XPO1-mediated nuclear export, resulting in nuclear retention and reactivation of tumor suppressor proteins (TSPs), inhibition of nuclear export of oncoprotein mRNAs (e.g., c-Myc, cyclin D1, Bcl-2), and restoration of glucocorticoid receptor (GR) signaling, especially in the presence of dexamethasone[2][3][4]. - **Carfilzomib** irreversibly inhibits the chymotrypsin-like activity of the 20S proteasome, preventing degradation of proteins involved in cell cycle control and apoptosis[3]. - **Dexamethasone** enhances the antitumor effect through GR-mediated apoptosis and is synergistic with selinexor[2][3]. **Primary indication**: Relapsed/refractory multiple myeloma (RRMM), including in patients with disease refractory to proteasome inhibitors, immunomodulatory agents, and other classes, as well as those with high-risk cytogenetics[3][1][4][6]. **Clinical trials**: There are ongoing phase 1/2 studies evaluating safety, maximum tolerated dose (MTD), recommended phase 2 dose (RP2D), efficacy, and pharmacodynamics in RRMM[3][4][5][1].

Brand names

XKdSKd

Other names

selinexor + carfilzomib + dexamethasoneSKdXKd