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**Selinexor + dexamethasone + ixazomib** is an investigational oral triplet combination regimen studied primarily for the treatment of relapsed and/or refractory multiple myeloma. **Selinexor** is a first-in-class selective inhibitor of nuclear export (SINE) that blocks exportin 1 (XPO1), leading to nuclear retention of tumor suppressor proteins and induction of apoptosis in cancer cells. **Dexamethasone** is a synthetic glucocorticoid receptor agonist, commonly used as an anti-inflammatory and antineoplastic agent in hematologic malignancies. **Ixazomib** is a second-generation oral proteasome inhibitor that disrupts protein degradation, leading to apoptosis in plasma cells. The combination aims to exploit mechanistic synergies: selinexor's inhibition of XPO1 sensitizes cells to both proteasome inhibition and steroid-induced apoptosis, while dexamethasone and ixazomib potentiate selinexor’s activity through complementary pathways affecting cell survival and stress responses. This regimen is all-oral and was studied in a phase I clinical trial (NCT02831686) in heavily pretreated multiple myeloma patients, showing some efficacy (ORR ~22%) with manageable toxicities, including cytopenias and gastrointestinal effects[4][3][1][2].
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