selinexor + mezigdomide + dexamethasone

**Selinexor + mezigdomide + dexamethasone (SMd)** is an all-oral triplet combination under investigation for relapsed/refractory multiple myeloma (RRMM), particularly in triple-class exposed patients or those relapsed/ineligible for CAR-T or bispecific therapies. Selinexor is a first-in-class selective inhibitor of nuclear export (SINE) that inhibits **Exportin 1 (XPO1)**, blocking the nuclear export of tumor suppressor proteins, oncoproteins, and other cargoes, leading to their accumulation in the nucleus and induction of apoptosis in myeloma cells. Mezigdomide (CC-92480) is a next-generation **cereblon E3 ligase modulator (CELMoD)** that promotes the ubiquitination and proteasomal degradation of transcription factors **Ikaros (IKZF1)** and **Aiolos (IKZF3)**, enhancing anti-myeloma activity while potentially sparing T-cell function. **Dexamethasone**, a synthetic glucocorticoid, provides broad anti-inflammatory and cytotoxic effects via glucocorticoid receptor agonism. Preclinical synergy between XPO1 inhibition and CELMoD activity supports efficacy in high-risk disease (e.g., 17p deletion, extramedullary), with phase 1b/2 STOMP trial (NCT02343042, Arm 12) data showing manageable safety (selinexor 40-60 mg weekly, mezigdomide 0.3-1.0 mg daily) and promising responses in heavily pretreated patients.[1][2][3][4][5]

Brand names

Xpovio

Other names

SMd